Lipid compositions and methods of use thereof

Abstract

This disclosure provides a lipid composition and methods of use thereof.

Description

LIPID COMPOSITIONS AND METHODS OF USE THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to Swedish Patent Application No. SE 2430250-7, filed May 2, 2024, the disclosure of which is incorporated herein by reference.BACKGROUND

[0002] Semaglutide is a GLP-1 receptor agonist sold as an antidiabetic drug for use in the treatment of type 2 diabetes and as an anti-obesity agent. Semaglutide is considered a long- acting GLP-1 receptor agonist, and e.g., approved by the FDA as once- weekly injection and as a tablet for daily administration as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is also approved by the FDA as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg / m2 or greater (obesity) or 27 kg / m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., cardiovascular disease, hypertension, type 2 diabetes mellitus, or dyslipidemia). Additionally, there are signs that semaglutide may have an effect on neurodegenerative diseases as well as for the treatment of substance use disorder such as alcohol and opioid use disorder. The most common side effects with semaglutide treatment are nausea, diarrhea, abdominal pain and constipation. Semaglutide has in rodents been shown to cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC).

[0003] Semaglutide is available as once-weekly injections, and it would be beneficial to have an even longer duration such as a once-monthly injection.SUMMARY

[0004] This disclosure provides, in part, a composition comprising from about 0.5 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2- pyrrolidone, N-methyl-2-pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol.

[0005] Additionally provided is a method of treating a disease of condition comprising administering to a mammalian patient in need thereof a composition comprising from about 0.5 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide. N-ethyl-2- pyrrolidone, N-methyl-2-pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol.

[0006] Additionally provided is a method of treating a mammalian patient suffering from a disease, condition, or a symptom thereof wherein a first dose of a composition comprising from about 0.5 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzy l alcohol, benzy l benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol to the mammalian patient, and wherein a second dose of the composition is administered after about two to five weeks of the administration of the first dose, and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the first dose. Optionally a third and an optional subsequent dose is administered in the same amount or greater as the second dose and after about two to five weeks of the administration of the latest dose.

[0007] Further provided is a pre-filled syringe comprising a composition comprising from about 0.5 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2- pyrrolidone, N-methyl-2-pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol, for use in treating a disease, and wherein the composition is administered to a patient once about every four weeks.

[0008] Further provided is an autoinjector comprising a compartment containing a composition from about 0.5 mg to about 50 mg of semaglutide, or an equivalent amount of apharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol, for use in treating a disease, and wherein the composition is administered to a patient once about every four weeks.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIG. 1 illustrates the pharmacokinetic profde (0-672 h), of semaglutide in two formulations in comparison with a semaglutide formulation comparable to marketed injectable semaglutide products.

[0010] FIG. 2 illustrates the pharmacokinetic profile (0-168 h), of semaglutide in two formulations in comparison with a semaglutide formulation comparable to marketed injectable semaglutide products.

[0011] FIG. 3 illustrates the mean plasma concentration (0-672 h), of semaglutide in four formulations with a semaglutide according to the present disclosure.

[0012] FIG. 4 illustrates the semaglutide (mean Cmax) concentration vs the phosphatidyl choline content in four formulations S32, S33, S34 and S15.

[0013] DETAILED DESCRIPTION

[0014] The features and other details of the disclosure will now be more particularly described. Before further description of the present disclosure, certain terms employed in the specification, examples and appended claims are collected here. These definitions should be read in light of the remainder of the disclosure and understood as by a person of ordinary’ skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary’ skill in the art.DEFINITIONS

[0015] '‘Treating” includes any effect, e.g., lessening, reducing, modulating, or eliminating, that results in the improvement of the condition, disease, disorder, and the like.

[0016] “Individual,” “patient,” or “subject” are used interchangeably and include any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans. The semaglutide and its salts (compound) can be administered to a mammal, such as a human, but can also be other mammalssuch as an animal in need of veterinary' treatment, e.g., domestic animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, sheep, pigs, horses, and the like) and laboratory- animals (e.g., rats, mice, guinea pigs, and the like).

[0017] The term “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” as used herein refers to any and all solvents, dispersion media, coatings, isotonic and absorption delaying agents, and the like, that are compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is yvell known in the art.

[0018] The term “pharmaceutical composition” as used herein refers to a composition comprising at least one compound as disclosed herein formulated together with one or more pharmaceutically acceptable carriers.

[0019] In the present specification, the term “therapeutically effective amount” means the amount of the subject compound that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by the researcher, veterinarian, medical doctor or other clinician. The compounds of the disclosure are administered in therapeutically effective amounts to treat a disease. Alternatively, a therapeutically effective amount of a compound is the quantity required to achieve a desired therapeutic and / or prophylactic effect, such as an amount which results in the treatment of one or more of the diseases listed herein.

[0020] Steady state is the time during which the concentration remains stable or consistent when the drug is given repeatedly. The steady state for the administration of the semaglutide compositions disclosed herein is estimated in healthy volunteers to be in the range of 2-3 months, such as about 2 months.

[0021] Whenever a dose or administration of an amount or dose is used in the current specification, it should be understood as the specified dose refers to semaglutide or a pharmaceutically acceptable salt thereof, e.g., 5 mg of the composition is administered to a patient should be understood as 5 mg of semaglutide or a pharmaceutically acceptable salt thereof, comprised in a lipid composition as described herein, is administered.

[0022] All % are specified by weight herein throughout, unless otherwise indicated. Percent (%) by weight may be abbreviated e.g., as wt%. Furthermore, the % by weight indicated is the % of the total composition including all the components indicated herein, unless otherwise indicated.

[0023] Whenever a range is used, it is to be understood that each individual listing is explicitly included. For example, in the Itemized List of Embodiments, the range of E8 - El 0 3, for example, would be understood to mean and include E8, E9, E10, E10_l, E10_2, and E10_3.Methods

[0024] The disclosure provides, in part, method of treating a disease, condition, or a symptom thereof selected from the group consisting of Alzheimer's disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus, obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction- associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular disorders, stroke, inflammatory bowel syndrome, dyspepsia, Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder or opioid use disorder by administering, to a subject in need thereof, a lipid composition comprising from about 0.5 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents and, 0.5 wt% - 15 wt% glycerol. In some embodiments the administration is once every’ two to five weeks, such as once every 28 days ± 7 days, such as once every 28 days ± 6 days, such as once every’ 28 days ± 5 days, such as once every 28 days ± 4 days, such as once every 28 days ± 3 days, such as once every’ 28 days ± 2 days, such as once every 28 days ± 1 days.In some embodiments the administration is once every four weeks, such as once every 28 days ± 3 days, such as once every' 28 days ± 2 days, such as once every' 28 days ± 1 days, such as once every’ 28 days. In an embodiment the method is for treating diabetes (type 1 or ty pe 2 diabetes mellitus and / or obesity.Compounds

[0025] The active agent in the present disclosure is semaglutide, which is a human GLP-1 receptor agonist (or GLP-1 analog). Structurally it is a modified analogue of glucagon-like peptide l-(7-37) with amino acids at positions 8 and 34 replaced by a-aminobutyric acid and arginine respectively, and Lys26is modified with a hydrophilic spacer and a C18 fatty di-acid. The molecular formula is C187H291N45O59 and the molecular weight is 4113.58 g / mol. The chemical abstract number is 910463-68-2.

[0026] The injectable lipid composition comprising from about 0.5 mg to about 50 mg of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is made up of about 10 to about 95 wt% lipids, e.g., about 15 to about 94 wt% lipids, about 20 to about 94 wt% lipids, about 30 to about 90 wt% lipids, e.g., about 40 to about 90 wt% lipids, about 50 to about 88 wt% lipids, about 55 to about 87 wt% lipids, about 60 to about 85 wt% lipids, about 65 to about 84 wt% lipids. Ratios of lipids, may in the case of PC : GDO be 60:40 to 40:60 (e.g., 45:55 to 55:45, 40:60 to 55:45, 45:55 to 54:46, 47:53 to 53:47), or ratios of around 50:50 (e.g., 49:51 to 51:49).

[0027] Example of lipids making up the lipid compositions disclosed herein are diacyl glycerols (e.g., glycerol dioleate) and phosphatidylcholine (e.g., soy phosphatidylcholine). Other possible lipids are for example monoacyl glycerol, triacyl glycerol, phosphatidyl glycerol, phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, lysophosphatidyl choline, phosphatidic acid, fatty acid. When the composition comprises a solvent or a mixture of solvents, e.g., ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2- pyrrolidone, N-methyl-2-pyrrolidone, glycerol, acetic acid, lactic acid, and water. The solvent may be present in a total amount of about 5 - about 45 wt%. e.g., about 8 - about 25 wt%, e.g., about 10 - about 24 wt%, e.g., about 10 - about 22 wt%, e.g., about 11 - about 21 wt%, e.g., about 12 - about 21 wt%. The lipid composition optionally includes additional excipients such as stabilizing agents, antioxidants, etc. The composition may contain water, although in some aspect of the present disclosure the water content of the lipid composition at release of the product is not more than (NMT) 2 wt%, such as 1 wt%, determined by USP<921>. The inactive excipients, i.e., the lipids, such as diacyl glycerol, e.g., glycerol dioleate and phosphatidyl choline, the solvent and / or solvent mixture and the optional additional excipients adds up to at least 70 wt%, such as 80 wt%, such as at least 85 wt% such as at least 90 wt% of the total drug product. The rest are for example by-products, for example, originating from the lipids. Glycerol dioleate (GDO) may also contain monoglycerides (NMT 2%) and triglycerides (NMT 5%). Generally, the GDO used in the lipid composition should contain at least about 93% glycerol dioleate. Phosphatidyl choline may also contain lysophosphatidylcholine (NMT 3%) and triglycerides (NMT 2%). Generally, the phosphatidyl choline used in the lipid composition should contain at least about 94% phosphatidyl choline.

[0028] The lipid composition is in some embodiments provided in a pre-filled syringe, e.g., a glass syringe, equipped with a small needle compared to the comparative product (22G), andthe drug product is not necessary to be reconstituted and considered ready-to-use. Suitable syringes may be those having a volume of about 0. 1, about 0.2, about 0.3. about 0.4, about 0.5, about 0.75, about 1.0, about 1.25, and about 1.5 mL. One example is a 1 rnL glass syringe, optionally equipped with a small needle compared to the comparative product (22G). An additional example is a suitable auto-injector, e.g., an auto-injector suitable for a glass syringe or glass cartridge. An additional example is a pen injector.

[0029] The present disclosure also relates to a lipid composition comprising, consisting essentially of, or consisting of from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzy l alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol.

[0030] The present disclosure also relates to an injectable lipid composition comprising, consisting essentially of, or consisting of from about 3 mg / mL to about 25 mg / mL of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2-pyrrolidone, N-methyl-2- pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol. In some aspects, the compositions disclosed herein have a semaglutide concentration about 5 mg / mL, about 10 mg / mL, about 15 mg / mL, about 20 mg / mL.

[0031] In many aspects of the present disclosure the lipid composition is substantially nonaqueous, e.g., it contains less than 3 wt% water, such as less than 2 wt% water, such as less than 1 wt% water.

[0032] The injectable lipid compositions disclosed herein may form a depot composition upon contact with an aqueous fluid. The term “depof ’ relates to the composition which is formed upon exposure of the lipid composition to excess aqueous fluid, e.g., as occurs during numerous parenteral administration routes, such as administration in the subcutaneous tissue of a human patient. The depot typically has a much higher viscosity than the corresponding lipid composition and provides for the gradual release of the semaglutide contained in the depot.Diacyl glycerol

[0033] The injectable lipid composition contains diacyl glycerol and a suitable example thereof is glycerol dioleate (GDO). The GDO may be present in the lipid composition in an amount ranging from 20 to 90 wt% of the lipid composition (e.g., 30 to 70 wt%, 33 to 60 wt%, 43 to 60 wt%, 38 to 43 wt%).

[0034] Suitable diacyl glycerols, such as GDO may be derived from natural sources, there is generally a certain proportion of ’contaminant" lipid having other chain lengths, etc. In this context, "pure" GDO is a di-ester of glycerol and two Cl 8: 1 fatty acids. Any other diacyl glycerol is considered to be an impurity. In one aspect, GDO, as used herein, indicates any commercial grade of GDO with concomitant impurities (i.e., GDO of commercial purity ). These impurities may be separated and removed by purification but, providing the grade is consistent, this is rarely necessary. If necessary, however. “GDO” may be essentially chemically pure GDO, such as at least 70% pure GDO (e g., at least 75% pure, at least 80% pure, at least 85% pure, at least 90% pure, at least 93%, at least 95% pure, at least 98% pure, at least 99% pure (area%). In some embodiments, the diglycerides content of the glycerol di oleate is about 92% - 100%, such as about 93% to about 99%. The GDO used herein should have an oleic acid content (Cl 8: 1) of at least 80% (e.g., at least 85%, at least 90%, at least 95%, at least 98%, at least 99%). In some embodiments, the diglyceride content is about 93% to about 99%, and the oleic acid content is about 88% to about 99% (area%). Diacyl glycerol other than GDO, or mixtures of GDO and other diacyl glycerols are also useful.

[0035] Any material used in the lipid composition, including GDO, may potentially include unavoidable trace impurities of metals, optionally including heavy metals. A typical maximum concentration of heavy metals (or elemental impurities) in diacyl glycerol, e.g., GDO, is 5 ppm.

[0036] In alternative embodiments, GDO may be replaced by, or combined with, at least one other lipid, e.g.. at least one fatty acid and / or fatty acid ester (lipid). Fatty acids / lipids contain a polar carboxylic acid or ester “head group” with the hydrocarbon chain forming a non-polar “tail” group. Fatty acid esters are esterified fatty acids. Fatty acids or esters used in the lipid composition may be solid or liquid at room temperature and pressure. Examples of non-polar “tail” groups include C6-C32 alkyl and alkenyl groups, which are typically present as long chain carboxylic acids or the esters thereof. These are often described by reference to the number of carbon atoms and the number of unsaturations in the carbon chain. Thus, CX:Z indicates a hydrocarbon chain having X carbon atoms and Z unsaturations. Examples particularly include caproyl (C6:0), capryloyl (C8:0). capryloyl (C10:0), lauroyl (C12:0), myristoyl (C14:0), palmitoyl (C16:0). phytanoyl (C16:0), palmitoleoyl (C16: l). stearoyl(C18:0), oleoyl (C 18: 1), elaidoyl (C18: 1), linoleoyl (C18:2), linolenoyl (C18:3), arachidonoyl (C20:4), behenoyl (C22:0), and lignoceroyl (C24:9) groups. When reference is made herein to the number of carbon atoms in the ‘’chain” or “tail” this number includes the carbon atom of the -C(O)O-moiety, as is conventional in the art.

[0037] Thus, typical non-polar chains are based on the fatty acids of natural ester lipids, including caproic, caprylic, capric, lauric, myristic, palmitic, phytanic, palmitolic, stearic, oleic, elaidic, linoleic, linolenic, arachidonic, behenic, or lignoceric acids, or the corresponding alcohols.

[0038] The lipid(s) may be saturated or unsaturated. For example, the lipid(s) may comprise at least 1 wt% unsaturated lipid (based on the total lipid content) (e.g., at least 5 wt% (5-100%), at least 15 wt% (15-100%). at least 30 wt% (30-100%), at least 50 wt% (50-100%), at least 80 wt% (80-100%)).

[0039] GDO may be replaced or combined with, for example, an edible lipid such as almond oil, avocado oil, butter, canola oil. castor oil, coconut oil, corn oil, cottonseed oil, flaxseed oil, ghee, lard, linseed oil, macadamia oil, margarine, mustard oil, olive oil, palm oil, peanut oil, pumpkin seed oil, rice bran oil, safflower oil, sesame oil, soybean oil, sunflower oil, tea seed oil, vegetable oil, or walnut oil.

[0040] One particular example is tocopherol, which may be used to replace GDO, or tocopherol may be used in combination with GDO, e.g., in a ratio of tocopherol to GDO of 30:70; 40:60 or 50:50.

[0041] When GDO is replaced by at least one other lipid, the at least one lipid may be present in the lipid composition in an amount ranging from 20 to 90 wt% of the lipid composition (e.g., 30 to 70 wt%, 33 to 60 wt%, 43 to 60 wt%, 38 to 43 wt%). If the lipid composition contains both GDO and at least one additional lipid, the combination may also be present in the lipid composition in an amount ranging from 20 to 90 wt% of the lipid composition (e.g., 30 to 70 wt%, 33 to 60 wt%, 43 to 60 wt%, 38 to 43 wt%).Phosphatidyl Choline (PC)

[0042] The lipid composition topically also contains phosphatidyl choline (PC). When present PC is present in an amount ranging from 20 to 80 wt% of the lipid composition (e.g., 30 to 70 wt%, 33 to 55 wt%, 35 to 55 wt%, 38 to 43 wt%). Ratios of GDO : PC may be 40:60 to 70:30 (e.g., 45:55 to 55:45, 40:60 to 54:46, 45:55 to 54:46, 47:53 to 53:47). Ratios of around 50:50 (e.g.. 49:51 to 51 :49) may be highly effective.

[0043] In alternative embodiments, PC may be replaced by, or combined with, at least one other phospholipid. The phospholipids may be derived from a natural source. In the case of PC, suitable sources of phospholipids include egg, heart (e.g., bovine), brain, liver (e.g., bovine), and plant sources, including vegetable PC, such as soybean. Such sources may provide one or more constituents of the PC and / or at least one other phospholipid. Any single PC or mixture thereof may be used according to the present disclosure, although egg, heart (e.g., bovine), brain, liver (e.g., bovine), and plant sources, including vegetable PC, such as soybean or any mixture thereof are used in most embodiments disclosed herein.

[0044] The PC may be derived from soy. The PC may comprise 18:2 fatty' acids as the primary' fatty acid component with 16:0 and / or 18: 1 as the secondary fatty' acid components. These may be present in the PC at a ratio of between 1.5: 1 and 6: 1. PC having approximately 60-65% 18:2, 10 to 20% 16:0, 5-15% 18:1 , with the balance predominantly' other 16 carbon and 18 carbon fatty' acids may be used, e.g., soy PC. In some embodiments, the PC has a purity of not less than 90%, not less than 92%, not less than 94%, such as about 94% - 100% (based on dry weight). The maximum lysophosphatidylcholine content is about 3%, e g., not more than 3%. The maximum triglycerides content is about 2%, such as not more than 2%. In some embodiments, the PC used in the lipid composition has a purity of about 94% - 100% (based on dry' weight) and contains not more than 3% lysophosphatidylcholine and optionally not more than 2% triglycerides.

[0045] Alternatively, the PC component may comprise synthetic dioleoyl PC (DOPC). The use of DOPC may provide increased stability and so may be used for compositions needing to be stable to long term storage, and / or having a long release period in vivo. Here, the PC component may contain at least 50% synthetic dioleoyl PC (e.g., at least 75% synthetic dioleoyl PC) and even essentially pure synthetic dioleoyl PC. Any remaining PC can be of any sort. DOPC may be more expensive.

[0046] Alternative types of phospholipids are synthetic or highly purified PCs, such as dioleoyl phosphatidy l choline (DOPC), may, in alternative embodiments, be used as all or part of the phospholipid component. The synthetic dioleoyl PC may be 1.2-dioleoyl-sn-glycero-3- phosphocholine, and other synthetic PC components include DDPC (1,2-Didecanoyl-sn- glycero-3-phosphocholine); DEPC (l,2-Dierucoyl-sn-glycero-3-phosphocholine); DLOPC (l,2-Dilinoleoyl-sn-glycero-3-phosphocholine); DLPC (l,2-Dilauroyl-sn-glycero-3- phosphocholine); DMPC (l,2-Dimyristoyl-sn-glycero-3-phosphocholine); DOPC (1,2- Dioleoyl-sn-glycero-3-phosphocholine); DPPC (1.2-Dipalmitoyl-sn-glycero-3-phosphocholine); DSPC (l,2-Distearoyl-sn-glycero-3-phosphocholine); MPPC (1-Myristoyl-2-palmitoyl-sn-glycero 3-phosphocholine); MSPC (l-Myristoyl-2-stearoyl-sn-glycero-3- phosphocholine); PMPC (l-Palmitoyl-2-myristoyl-sn-glycero-3-phosphocholine); POPC (1- Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine); PSPC (1 -Palmitoyl-2-stearoyl-sn-glycero-3-phosphocholine); SMPC (l-Stearoyl-2-myristoyl-sn-glycero-3-phosphocholine); SOPC (1- Stearoyl-2-oleoyl-sn-glycero-3-phosphocholine); and SPPC (l-Stearoyl-2-palmitoyl-sn- glycero-3-phosphocholine), or any combination thereof.

[0047] Alternative lipid compositions that may be used in the present disclosure are disclosed in WO2016 / 066655, which is incorporated herein by reference, where lipid slow- release matrices based on triacyl lipids that can form depot compositions on exposure to aqueous fluids without the need for a phospholipid component to be present, though in certain embodiments a phospholipid may also be present.

[0048] Alternative embodiments include phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylinositol, instead of phosphatidyl choline.

[0049] Since the injectable lipid compositions are to be administered to a subject, such as a patient, with the inclusion of semaglutide, the components should be biocompatible. In this regard, PC (such as soy PC and / or DOPC) and GDO are useful, since they are well tolerated and are broken down in vivo into components that are naturally present in the mammalian body. Appropriate amounts of each component suitable for the combination are those amounts indicated herein for the individual components in any combination. This applies also to any combinations of components indicated herein, where context allows.

[0050] When PC is replaced by at least one other phospholipid, the at least one phospholipid may be present in the lipid composition in an amount ranging from 20 to 80 wt% of the lipid composition (e.g., 30 to 70 wt%, 33 to 55 wt%, 35 to 55 wt%, 38 to 43 wt%). If the lipid composition contains both PC and at least one additional phospholipid, the combination may also be present in the lipid composition in an amount ranging from 20 to 80 wt% of the lipid composition (e.g., 30 to 70 wt%, 33 to 55 wt%, 35 to 55 wt%, 38 to 43 wt%). Ratios of GDO and / or the at least one lipid other than GDO : PC and / or the at least one phospholipid other than PC may be 40:60 to 70:30 (e.g.. 45:55 to 55:45, 40:60 to 54:46, 45:55 to 54:46, 47:53 to 53:47). Ratios of around 50:50 (e.g., 49:51 to 51 :49) may be highly effective.Solvent

[0051] The lipid composition also contains a solvent, e.g., ethanol, benzyl alcohol, benzy l benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide,N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidone, glycerol, acetic acid, lactic acid, water or a mixture thereof. In many embodiments, ethanol is a suitable solvent. Ethanol may be replaced by, or combined with, at least one other biocompatible organic solvent. Since the lipid composition may generate a depot composition following administration (e.g., in vivo), typically upon contact with excess aqueous fluid, it is desirable that this solvent be tolerable to the subject and be capable of mixing with the aqueous fluid, e.g., body fluids, and / or diffusing or dissolving out of the lipid composition into the aqueous fluid. Therefore, solvents having at least moderate water solubility may be used. In some embodiments the lipid compositions include a polar solvent. Typically, a level of 1 to 45% (e.g., 2 to 25%, 5 to 22%, 5 to 20%, 2 to 15%, 4 to 15%, 5 to 15%) solvent will provide suitable release and viscosity properties.

[0052] In alternative embodiments, instead (or in addition to) ethanol, the solvent in the lipid composition comprises, consists essentially of, or consists of at least one solvent selected from the group consisting of: alcohols, amines, amides, and esters. Therefore, the solvent may comprise at least a mono-alcoholic solvent, such as ethanol, propanol, iso-propanol, or mixtures thereof. In one embodiment, the solvent is ethanol. The lipid composition may also comprise, consist essentially of, or consist of a mono-alcoholic solvent (e.g., ethanol) and a polar solvent (e.g., propylene glycol). The amount of solvent in the lipid composition may affect several features, including, for example, the viscosity and the rate (and duration) of release. Therefore, the amount of solvent may be at least sufficient to provide a low viscosity mixture but may additionally be determined so as to provide the desired release rate. Typically, a level of 1 to 30% (e.g., 2 to 20%, 2 to 18%, 2 to 16%, 2 to 15%, 4 to 15%, 5 to 15%,) solvent will provide suitable release and viscosity' properties. In some embodiments, the solvent consists of EtOH at a level of 3 - 15%, and, PG at a level of 3 - 15%.

[0053] In some embodiments, the total amount of solvent is at a level of 10 - 55%, e.g., 10-25%, such as 12-22 wt%.

[0054] In some embodiments, the solvent contains, EtOH, at a level of 3 - 15%, and, PG, at a level of 3 - 15%, and the total amount of solvent and co-solvent is at a level of 10 - 35%, e.g., 10-25%, such as 12-22 wt%.

[0055] As indicated above, the amount of solvent in the lipid compositions may be at least sufficient to provide a low viscosity mixture (e.g., a molecular solution) of the components of the lipid composition and can be determined for any particular combination of components by standard methods.

[0056] The solvent may be a single solvent (e.g., ethanol) or a mixture of suitable solvents (e.g., ethanol and PG) but will generally be of low viscosity. In some embodiments the solvent is a mixture of ethanol and propylene glycol, and glycerol. The viscosity of the ‘'low viscosity" solvent (single solvent or mixture) may be no more than 18 rnPas at 20°C (e.g., no more than 15 rnPas at 20°C, no more than 10 mPas at 20°C, no more than 7 rnPas at 20°C).

[0057] W02012 / 160213 describes the addition of a polar solvent in addition to a monoalcoholic solvent results in numerous advantages including reduced viscosity and reduced active agent burst profile. In addition to the aspects described previously for the solvent component, in some embodiments, the solvent comprises a mono-alcoholic solvent (e.g., ethanol) and a polar co-solvent. The term “polar co-solvent” or “polar solvent” as used herein defines a solvent having a dielectric constant (diel) of at least 28 at 25°C (e.g., at least 30 at 25°C) but is not water or any aqueous fluid. Examples include propylene glycol (diel about 32), and N-methyl-2-pyrrolidone (NMP, diel about 32). The levels of solvent recited herein may apply equally to mixtures of mono-alcoholic solvent and a polar co-solvent unless context permits otherwise.

[0058] In another embodiment, the solvent comprises, consists essentially of, or consists of a mixture of a mono-alcoholic solvent and a polar co-solvent. The polar co-solvent may be a di -alcoholic C3-C6 organic solvent, i.e., a C3-C6 organic solvent comprising two hydroxy groups. The di-alcoholic solvent may be propylene glycol. When present, a polar co-solvent may be included at a level of 2 to 12 wt% of the lipid composition (e.g., 3 to 10 wt%, 4 to 9 wt%). This level is counted as part of the ranges recited above for the solvent. In one embodiment, the solvent comprises, consists essentially of, or consists of a mixture of ethanol and propylene glycol (PG), where PG is considered a co-solvent.

[0059] Where both an organic mono-alcoholic solvent and a polar co-solvent are present, e.g., ethanol and PG, the ratio of mono-alcoholic solvent to polar co-solvent solvent may be in the range 20:80 to 70:30 (w / w) (e.g., 30:70 to 70:30 (w / w), 40:60 to 60:40 (w / w)). The amounts and ratio of ethanol and PG may have an effect on properties such as release of an active agent, viscosity of the lipid composition, etc., features which are all important characteristics of suitable lipid compositions for subcutaneous injection of an active agent to a patient in need thereof.

[0060] In one embodiment, the total amount of solvent is at a level of 1 to 45 wt% (e.g., 5 to 15 wt%, 8 to 18 wt%, 8 to 18 wt%) and comprises, consists essentially of, or consists of a mixture of ethanol and PG, wherein the ratio of ethanol to PG (w / w) is in the range of 30:70 to70:30 (w / w) (e.g., 40:60 to 60:40 (w / w)). Additional examples are about 5-15 wt% ethanol and about 5-15 wt% PG, e.g., about 5-12 wt% of each of ethanol and PG.

[0061] In an embodiment the solvent is selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidone, glycerol, acetic acid, lactic acid, water, and a mixture thereof.

[0062] In an embodiment the solvent is selected from the group consisting of ethanol, and / or propylene glycol, dimethyl sulphoxide, and / or glycerol.

[0063] In an embodiment the solvent is selected from the group consisting of ethanol, ethanol / PG, and glycerol.

[0064] In an embodiment of the present disclosure the injectable lipid compositions disclosed herein comprise or consist of a solvent mixture. The solvent mixture has been shown to have a positive effect on the inj ectable lipid compositions whenever the mixture is ethanol, and / or propylene glycol, and glycerol. It has been demonstrated that lipid compositions disclosed herein reduce the known aggregation effect of compositions comprising semaglutide. An aggregation effect may have an impact on the release properties of injectable composition of semaglutide, and the present disclosure demonstrates that an appropriate solvent mixture, e.g., a mixture of ethanol, propylene glycol, and glycerol, reduces the aggregation effect in lipid compositions. Injectable lipid compositions disclosed herein, e.g., injectable pharmaceutical composition comprising from about 2 mg to about 50 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, and / or propylene glycol and further comprising 0.5 wt% - 15 wt% glycerol provides a composition suitable for about monthly (such as about once every’ 4 week, such as once about every 28 days ± 7 days, such as 28 days ± 3 days). Additionally, embodiments of the present disclosure comprising one or more pharmaceutically acceptable lipid excipients (e.g., comprising glycerol dioleate and phosphatidyl choline), solvents (e.g., ethanol, and / or propylene glycol), and further comprising 0.5 wt% - 15 wt% glycerol provides a composition comprising drug loads sufficient for monthly administration.

[0065] Injectable lipid compositions disclosed herein, e.g., injectable pharmaceutical composition comprising from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, andpropylene glycol, and further comprising 0.5 wt% - 15 wt% glycerol provides a composition suitable for about monthly (such as about once every 4 week, such as once about every 28 days ± 5 days), which has a reduced aggregation compared to other lipid compositions.

[0066] Injectable lipid compositions disclosed herein, e.g., injectable pharmaceutical composition comprising from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, and propylene glycol and further comprising 0.5 wt% - 15 wt% glycerol provides a composition suitable for about monthly (such as about once every 4 week, such as once about every 28 days ± 7 days), has a delayed Cmax compared to products marketed, e.g., under the tradenames Wegovy and Ozempic. A delayed Cmaxmay provide a favorable pharmacokinetic profile with better tolerance and maintained pharmacodynamic effects, e.g., for about one month.

[0067] The term “release” in this context means released for administration to a patient, i.e.. a pharmaceutical product approved by a regulatory' agency, e.g., the FDA. The term release specification means the tests and limits against which raw material, intermediate, and final product are measured prior to use and / or release.Optional excipients

[0068] Besides the semaglutide or a pharmaceutically acceptable salt thereof, one or more lipids, and a solvent, the compositions disclosed herein may contain additional excipient(s).

[0069] Semaglutide in the compositions disclosed herein, may gain stability (both storage and in vivo stability ) by certain stabilizing additives. Such additives include, but are not limited to, sugars (e.g., sucrose, trehalose, lactose, etc.), polymers (e.g., polyols such as carboxy methyl cellulose), amino acids (such as methionine, glutamate, lysine, etc.), lipid-soluble acid components such as HC1, anionic lipids, and / or surface active agents (such as dioleoyl phosphatidyl glycerol (DOPG), palmitoyloleoyl phosphatidylglycerol (POPG), and oleic acid (OA)). Another example is EDTA (“ethylenediaminetetraacetic acid” or “edetic acid”). As used herein, the term “EDTA” may represent ethylenediaminetetraacetic acid as such. Alternatively, EDTA as indicated herein may include ethylenediaminetetraacetic acid itself, EDTA analogues, and alkylammonium EDTA salts. “EDTA” herein thus includes “EDTA, analogues thereof, and alkylammonium EDTA salts,” whenever context allows.

[0070] Examples of EDTA analogues include:Iminodiacetic acid (IDA) - (NH(CH2CO2H)2;Nitrilotriacetic acid (NTA) - N(CH2CO2H)3;Pentetic acid* - N(CH2CO2H)2CH2CH2N(CH2CO2H)CH2CH2N(CH2CO2H)2;Egtazic acid - N(CH2CO2H)2CH2CH2OCH2CH2OCH2CH2N(CH2CO2H)2;NOTA - [N(CH2CO2H)CH2CH2]3; andDOTA - [N(CH2CO2H)CH2CH2]4.* Also known as “DTP A”

[0071] EDTA analogues and alkylammonium salts thereof are further disclosed and described in WO 2018 / 060212, which is hereby incorporated herein by reference.

[0072] The alkylammonium salt(s) of EDTA is provided by contacting the EDTA or analogue thereof with a suitable alkylamine, examples are:Ethanolamine “ETA'’ (NH2(CH2CH2OH));Diethanolamine “DiETA” (NH(CH2CH2OH)2); meglumine (NH(CH3)CH2(CHOH)4CH2OH)); tris-hydroxymethylamine “TRIS” (N(CH2OH)3); ethylenediamine (NFECFECfENEh); and serinol (NH2CH(CH2OH)2).

[0073] An example of alkylammonium EDTA salt is EDTA with ethanolamine (ETA) (e.g., EDTA with ETA only).

[0074] The composition disclosed herein may also contain EDTA salts comprising an anion of EDTA and at least one alkylammonium cation of the suitable alkylamine as previously described. Further examples and details are available in WO 2018 / 060212, herein incorporated by reference.

[0075] In some embodiments, the compositions disclosed herein comprising semaglutide, do not include EDTA.

[0076] Single-dose formats, such as pre-filled syringes comprising lipid compositions disclosed herein, must remain stable and potent in storage prior to use but are disposable after the single use. The substantially non-aqueous lipid compositions have enhanced storage stability' at elevated temperatures, such as at 25°C or even 40°C.

[0077] A single dose format of the lipid composition may have a stability such that after storage for 2 months at 40°C (with air in head space), the assayed semaglutide concentration is at least 85% that of the initial assayed semaglutide concentration, and after 3 months, the assayed semaglutide concentration is at least 80% that of the initial assayed semaglutide concentration.

[0078] The compositions disclosed herein can optionally contain an antimicrobial or microbial-static agent, which includes bacteriostatic agents and preservatives. Such agents include benzalkonium chloride, m-cresol, benzyl alcohol, or other phenolic preservatives. Typical concentrations as known in the art can be used. In most aspects and embodiments, there are no antimicrobial or microbial-static agents added.

[0079] These additional components, if present, may be present in an amount of up to 5 wt% (e.g., 0.01 to 5 wt%), such as no more than 2% by weight, or no more than 1% by weight.

[0080] In some embodiments the composition comprises no additional excipient.Water content

[0081] It is difficult to eliminate all traces of water (especially from the raw materials). Even if essentially water-free formulations could be achieved, lipid compositions described in this disclosure will typically be stored in ready-to-use form, e g., in syringes and possibly under refrigerated conditions, or alternatively frozen conditions. Syringes are often not completely air-tight meaning that the level of w ater in the lipid composition may increase to an appreciable level over time, e.g., over months, even if the initial level of water is insignificant.

[0082] The initial absolute level of w ater in the lipid composition may be between 0 to about 2.0 wl% (e.g., less than about 1.0 wt%, less than about 0.9 wt%, less than about 0.8 wt%). For example, the level of water may be in the range of about 0.1 to about 0.9 wt%, such as about 0.2 to about 0.8 wt%, or about 0.1 to about 1.5 wt% wt%. These levels refer to the absolute level of water and not added levels of water. Any unavoidable trace of water present within the components of the lipid composition is included in this stated level of water. After 3 months of storage, the absolute w ater level may be no more than 1.5 wt%. Absolute levels of water can be measured by methods well known in the art, such as Karl Fischer titration. For example, the water content may be measured according to the procedure in United States Pharmacopoeia (USP 40 - NF 35, USP <921> Water determination. Method la).

[0083] The compositions disclosed herein have a water content of between 0 to 3.0 wt% (e.g., less than about 2 wt%, less than about 1.5 wt%, less than about 1.0 wt%, less than about 0.8 wt%), e.g., when the lipid composition product is released for sale (e.g., released for administration to a patient).

[0084] In some embodiments the lipid composition disclosed herein is intended for refrigerated storage, e.g., in order to achieve suitable stability the injectable lipid composition comprising semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof, e.g., a lipid composition as disclosed herein provided in a syringe, such as a glass syringe, or aglass container for an injection device, such as an auto-injector is stored at refrigerated conditions refrigerated conditions, or alternatively frozen conditions. In some aspects the stability of the lipid composition comprising semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof fulfilling regulatory stability requirements for at least six months, such as at least 12 months, such as at least 18 months upon storage at 2-8°C (refrigerated conditions).

[0085] Exemplary Embodiments

[0086] The present disclosure relates to a method of treating at least one disease, condition or a symptom thereof comprising, consisting essentially of, or consisting of administering to a patient in need thereof a lipid composition from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, as an active ingredient and one or more pharmaceutically acceptable lipid excipients once every three to five weeks, such as once every 28 days ± 7 days, such as once every 28 days ± 6 days, such as once every 28 days ± 5 days, such as once every 28 days ± 4 days, such as once every 28 days ± 3 days, such as once every 28 days ± 2 days, such as once every 28 days ± 1 days. A suitable administration is once every 4 weeks, such as such as once every 28 days ± 3 days, such as once every 28 days ± 2 days, such as once every 28 days ± 1 days, such as once every 28 days. An example is once every four weeks.

[0087] The lipid compositions, which are described herein, may be administered to the patient once every four weeks as a single unit-dose, or in multi-dose formats, often a single unit-dose is preferred for the patient.

[0088] In one embodiment the injectable lipid compositions substantially comprise the following components: 1-50 mg (or about 1.25, 2.5, 5, 10, 15 or 20 mg) of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof, 5-45 wt% solvents, e.g., ethanol, and / or propylene glycol (PG), and glycerol, and 30 to 50 \\t% glycerol dioleate (GDO), and 30 to 50 wt% phosphatidyl choline (PC), e.g., soy phosphatidyl choline (SPC).

[0089] In one embodiment the inj ectable lipid composition may substantially comprise the following components: 1.25-20 mg (e.g., 1.25 mg, 2.5 mg, 5 mg. 10 mg. 15 mg or 20 mg) of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof, 8-30 wt% solvents, e.g., ethanol, and / or propylene glycol (PG) (e.g., a 1:2-2: 1 wt% mixture of ethanol and PG), and about 1-7 wt% glycerol, and 30 to 50 wt% diacyl glycerol, and 30 to 50 wt% phosphatidyl choline (PC), e.g., soy phosphatidyl choline (SPC).

[0090] The disease, condition or a symptom thereof is Alzheimer's disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus, obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary’ heart disease and other cardiovascular disorders, stroke, inflammatory' bowel syndrome, dyspepsia, Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder and opioid use disorder. In an embodiment the disease is ty pe 2 diabetes mellitus. In an embodiment the disease is impaired glucose tolerance. In an embodiment the disease is type 1 diabetes mellitus. In an embodiment the disease is obesity. In some embodiments, the disease is substance use disorder.

[0091] The lipid composition may be administered to the patient by subcutaneous injection. The lipid composition may be administered to the patient by a syringe, a pre-filled syringe, an autoinjector, or a pen injector. In one embodiment the lipid composition may be administered subcutaneously in the abdomen or thigh.

[0092] The lipid composition disclosed herein may be administered to the patient not more than once every four weeks, and in a volume of about 1 rnL, such as 1.0 mL, optionally the volume may be in the range of 0. 1 mL - 2 mL, such as 0. 1 mL, 0.2 mL, 0.3 mL, 0.4 mL, 0.5 mL, 0.6 mL, 0.7 mL. 0.8 mL, 0.9 mL, 1.0 mL, 1.1 mL, 1.2 mL, 1.3 rnL, 1.4 mL, and 1.5 mL.

[0093] The lipid formulation may be provided in a pre-filled syringe, e.g., a 1 mL glass syringe, equipped with a small needle, and the drug product is not necessary to be reconstituted and considered ready-to-use.

[0094] The lipid formulation comprising from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof may be provided in a pre-filled device suitable for injection, e.g., a syringe, e.g., a 1 mL glass syringe, equipped with a small needle, and wherein the pre-filled device comprising the lipid formulation comprising from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof is stored at refrigerated conditions, e.g., 2-8 °C.

[0095] The lipid formulation comprising from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof may be provided in a pre-filled device suitable for injection, e.g., a syringe, e.g., a 1 mL glass syringe, equipped with a small needle, and wherein the pre-filled device comprising the lipid formulation comprisingfrom about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof is stored at frozen conditions, e.g.. below 0 °C.

[0096] For each administration of the lipid composition of the present disclosure, the patient may have a maximum blood plasma concentration (Cmax) of semaglutide (at steady state) of 20 ng / mL (5 nmol / L) to about 1350 ng / mL (330 nmol / L), such as 20-1050 ng / mL (5- 255 nmol / L), such as 40-1200 ng / mL (10-290 nmol / L). such as 60-750 ng / mL (15-180 nmol / L). The Cmax of semaglutide at steady state is for example determined after 2 months of treatment. The concentration of semaglutide may be determined using ultra high-performance liquid chromatography-tandem mass spectrometry'.

[0097] Administration of the lipid composition disclosed herein provides a drug depot comprising semaglutide in the patient, wherein the depot provides a therapeutically effective dose of semaglutide to the patient over about four weeks. Optionally the patient may have blood plasma levels of semaglutide of at least about 15 nmol / L e.g., at least about 30 nmol / L, at least about 60 nmol / L, at least about 75 nmol / L during the about four weeks. The depot is e.g., provided in the subcutaneous tissue of the patient.

[0098] Administration of the lipid composition may provide a lipid drug depot comprising semaglutide e.g., in the subcutaneous tissue of the patient, and wh erein the depot may provide a therapeutically effective release of semaglutide to the patient over about 4 weeks.

[0099] Administration of the lipid composition disclosed herein provides a mean Cmax,ssin the range of about 62 ng / mL (15 nmol / L) to about 1350 ng / mL (330 nmol / L), such as 20-1050 ng / mL (5-255 nmol / L), such as 40-1200 ng / mL (10-290 nmol / L). In some embodiments the Cmax,ss in the range of about 60 ng / mL (15 nmol / L) to about 1050 ng / mL (255 nmol / L) in the mammalian patient.[000100] The method of administering the lipid composition comprising from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the administration is as a small-volume subcutaneous injection using, for example, a pre-fdled syringe (i.e., with or without the need for reconstitution) once every two to five weeks, such as once every- 28 days ± 7 days, such as once every 28 days ± 6 days, such as once every’ 28 days ± 5 days, such as once every 28 days ± 4 days, such as once every' 28 days ± 3 days, such as once every' 28 days ± 2 days, such as once every 28 days ± 1 days, wherein the provides a ready-to-use, long-acting semaglutide formulation, optionally with delayed Cmax compared to commercially available semaglutide products.[000101] The compositions and methods disclosed herein may result in a decreased exposure fluctuation which may translate into less the patient experienced nausea may be reduced by the present composition and methods disclosed herein.[000102] In some embodiments, disclosed herein is a kit for the administration of the injectable lipid composition of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof having one or more containers comprising about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzy l alcohol, benzy l benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2-pyrrolidone, N-methyl-2- pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol, wherein the composition in the one or more containers is administered according to the aforementioned method and / or any of its disclosed variations.Itemized List of Embodiments[000103] El. An injectable pharmaceutical composition comprising from about 0.5 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, one or more solvents selected from the group consisting of ethanol, benzyl alcohol, benzyl benzoate, propylene glycol, polypropylene glycol, polyethylene glycol, dimethyl sulphoxide, N-ethyl-2- pyrrolidone, N-methyl-2-pyrrolidone, acetic acid, lactic acid, and water, wherein the composition further comprises 0.5 wt% - 15 wt% glycerol.[000104] E2. The injectable pharmaceutical composition of El, wherein the composition comprises about 1 mg to about 25 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000105] E2_l . The injectable pharmaceutical composition of E2, wherein the composition comprises about 1.25 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000106] E2_2. The injectable pharmaceutical composition of E2, wherein the composition comprises about 1.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000107] E2_3. The injectable pharmaceutical composition of E2, wherein the composition comprises about 1.75 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000108] E3. The injectable pharmaceutical composition of E2, wherein the composition comprises about 2 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000109] E4. The injectable pharmaceutical composition of E2, wherein the composition comprises about 2.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000110] E6. The injectable pharmaceutical composition of E2. wherein the composition comprises about 3 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000111] E7. The injectable pharmaceutical composition of E2, wherein the composition comprises about 3.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000112] E8. The injectable pharmaceutical composition of E2, wherein the composition comprises about 4 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000113] E9. The injectable pharmaceutical composition of E2. wherein the composition comprises about 4.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000114] E10. The injectable pharmaceutical composition of E2, wherein the composition comprises about 5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000115] E12. The injectable pharmaceutical composition of E2, wherein the composition comprises about 5.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000116] El 3. The injectable pharmaceutical composition of E2, wherein the composition comprises about 6 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof.[000117] E14. The injectable pharmaceutical composition of E2, wherein the composition comprises about 6.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000118] El 5. The injectable pharmaceutical composition of E2, wherein the composition comprises about 7 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000119] E16. The injectable pharmaceutical composition of E2, wherein the composition comprises about 7.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000120] E17. The injectable pharmaceutical composition of E2, wherein the composition comprises about 8 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000121] El 8. The injectable pharmaceutical composition of E2, wherein the composition comprises about 8.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000122] E19. The injectable pharmaceutical composition of E2, wherein the composition comprises about 9 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000123] E20. The injectable pharmaceutical composition of E2, wherein the composition comprises about 9.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000124] E21. The injectable pharmaceutical composition of E2, wherein the composition comprises about 10 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000125] E22. The injectable pharmaceutical composition of E2, wherein the composition comprises about 10.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000126] E23. The injectable pharmaceutical composition of E2, wherein the composition comprises about 11 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000127] E24. The injectable pharmaceutical composition of E2, wherein the composition comprises about 11.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000128] E25. The injectable pharmaceutical composition of E2, wherein the composition comprises about 12 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000129] E25_l. The injectable pharmaceutical composition of E2, wherein the composition comprises about 12.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000130] E25_2. The injectable pharmaceutical composition of E2, wherein the composition comprises about 13 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof.[000131] E25 3. The injectable pharmaceutical composition of E2, wherein the composition comprises about 13.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000132] E25_4. The injectable pharmaceutical composition of E2, wherein the composition comprises about 14 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000133] E25_5. The injectable pharmaceutical composition of E2, wherein the composition comprises about 14.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000134] E25 6. The injectable pharmaceutical composition of E2, wherein the composition comprises about 15 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000135] E25_7. The injectable pharmaceutical composition of E2, wherein the composition comprises about 15.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000136] E25 8. The injectable pharmaceutical composition of E2, wherein the composition comprises about 16 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000137] E25_9. The injectable pharmaceutical composition of E2, wherein the composition comprises about 16.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000138] E25_10. The injectable pharmaceutical composition of E2, wherein the composition comprises about 17 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000139] E25 11. The injectable pharmaceutical composition of E2, wherein the composition comprises about 17.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000140] E25 12. The injectable pharmaceutical composition of E2, wherein the composition comprises about 18 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000141] E25 13. The injectable pharmaceutical composition of E2, wherein the composition comprises about 18.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000142] E25_14. The injectable pharmaceutical composition of E2, wherein the composition comprises about 19 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000143] E25 15. The injectable pharmaceutical composition of E2, wherein the composition comprises about 19.5 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof.[000144] E25 16. The injectable pharmaceutical composition of E2, wherein the composition comprises about 20 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000145] E25_17. The injectable pharmaceutical composition of E2, wherein the composition comprises about 20.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000146] E25_18. The injectable pharmaceutical composition of E2, wherein the composition comprises about 21 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000147] E25 19. The injectable pharmaceutical composition of E2, wherein the composition comprises about 21.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000148] E25_20. The injectable pharmaceutical composition of E2, wherein the composition comprises about 22 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000149] E25_21. The injectable pharmaceutical composition of E2, wherein the composition comprises about 22.5 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof.[000150] E25 22. The injectable pharmaceutical composition of E2, wherein the composition comprises about 23 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000151] E25 23. The injectable pharmaceutical composition of E2, wherein the composition comprises about 23.5 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof.[000152] E25 24. The injectable pharmaceutical composition of E2, wherein the composition comprises about 24 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000153] E25_25. The injectable pharmaceutical composition of E2, wherein the composition comprises about 24.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000154] E25_26. The injectable pharmaceutical composition of E2, wherein the composition comprises about 25 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000155] E26. The pharmaceutical composition of any one of El - E25 (i.e., El - E25 and E25_l - E25_26), wherein the composition comprises about 2.5 mg to about 20 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000156] E26_l. The pharmaceutical composition of any one of El - E25 (i.e.. El - E25 and E25_l - E25_26), wherein the composition comprises about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, or about 15 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000157] E27. The injectable pharmaceutical composition of any one of El - E26 (i.e., El - E25, E25_l - E25_26, E26, and E26_l), wherein the lipid excipients are selected from the group consisting of monoacyl glycerol, diacyl glycerol, triacyl glycerol, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, lysophosphatidyl choline, phosphatidic acid, fatty acid, sorbitan monooleate, sorbitan dioleate, and sorbitan trioleate.[000158] E27_l. The injectable pharmaceutical composition of any one of El - E26 (i.e., El- E25, E25_l - E25_26, E26, and E26_l), wherein the lipid excipients are selected from the group consisting of monoacyl glycerol, diacyl glycerol, triacyl glycerol, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, lysophosphatidyl choline, and phosphatidic acid.[000159] E27_2. The injectable pharmaceutical composition of any one of El - E26 (i.e., El- E25, E25_l - E25_26, E26, and E26_l), wherein the lipid excipients are selected from the group consisting of monoacyl glycerol, diacyl glycerol, phosphatidyl choline, phosphatidylglycerol, phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, lysophosphatidyl choline, and phosphatidic acid.[000160] E28. The injectable pharmaceutical composition of any one of El - E27_2, wherein the lipid excipients are diacyl glycerol and phosphatidyl choline.[000161] E29. The injectable pharmaceutical composition of any one of El - E28, wherein the one or more solvents is selected from ethanol or a mixture of ethanol and propylene glycol. [000162] E30. The injectable pharmaceutical composition of any one of El - E29, wherein the composition contains 5 wt% - 15 wt% ethanol, such as 7 wt% - 13 wt% ethanol, such as about 8 wt% - about 12 wt% ethanol, such as about 10 wt% ethanol.[000163] E31. The injectable pharmaceutical composition of any one of El - E30, wherein the composition contains about 8 wt% - 12 wt% ethanol.[000164] E32. The injectable pharmaceutical composition of any one of El - E30, wherein the composition contains about 9 wt% - 11 wt% ethanol.[000165] E33. The injectable pharmaceutical composition of any one of El - E30, wherein the composition contains about 10 wt% ethanol.[000166] E34. The injectable pharmaceutical composition of any one of El - E33, wherein the composition contains 5 wt% - 25 wt% PG, such as 5 wt% - 15 wt% PG, such as 5.5 wt% - 13 wt% PG, such as about 7.5 wt% - about 12.5 wt% PG, such as about 7.5 wt% - about 10.5 wt% PG, such as about 8.5 wt% PG or about 10 wt% PG.[000167] E35. The injectable pharmaceutical composition of any one of El - E33, wherein the composition contains about 5.5 wt% - about 12 wt% PG.[000168] E35_l. The injectable pharmaceutical composition of any one of El - E33, wherein the composition contains about 6 wt% - about 10 wt% PG.[000169] E36. The injectable pharmaceutical composition of any one of El - E33, wherein the composition contains about 7 wt% - about 9 wt% PG.[000170] E37. The injectable pharmaceutical composition of any one of El - E33, wherein the composition contains about 8.5 wt% PG.[000171] E38. The injectable pharmaceutical composition of any one of El - E37, wherein the composition contains about 0.7 wt% - about 12.5 wt% glycerol, such as about 1 wt% - about 10 wt% glycerol, such as about 1 wt% - about 7.5 wt% glycerol, such as about 1.5 wt%- about 7.5 wt% glycerol, such as about 1 wt% - about 5 wt% glycerol, such as about 1.5 wt%- about 4 wt% glycerol, such as about 1.5 wt% glycerol, about 2 wt% glycerol, about 3 wt% glycerol, about 4 wt% glycerol, or about 4.5 wt% glycerol.[000172] E39. The injectable pharmaceutical composition of any one of El - E37, wherein the composition contains about 1 wt% - about 5 wt% glycerol, such as about 1.5 wt% - about 5 wt% glycerol, such as about 1.5 wt% - about 4.5 wt% glycerol, such as about 1.6 wt% - about 4 wt% glycerol, such as about 1.7 wt% - about 3.8 wt% glycerol.[000173] E40. The injectable pharmaceutical composition of any one of El - E37, wherein the composition contains about 1 wt% - about 3 wt% glycerol.[000174] E41. The injectable pharmaceutical composition of any one of El - E37, wherein the composition contains about 2 wt% glycerol.[000175] E42. The injectable pharmaceutical composition of any one of El - E41, wherein the ratio of phosphatidyl choline to glycerol dioleate is in the range of about 60:40 - about 40:60, such as about 60:40 - about 45:55, such as about 55:45 - about 45:55, such as about 47:53 - about 53:46, such as about 50:50.[000176] E43. The injectable pharmaceutical composition of any one of El - E41, wherein the ratio of phosphatidyl choline to glycerol dioleate is in the range of about 55:45 - about 45:55.[000177] E44. The injectable pharmaceutical composition of any one of El - E41, wherein the ratio of phosphatidyl choline to glycerol dioleate is about 50:50.[000178] E45. The injectable pharmaceutical composition of any one El - E44, wherein at least 95 wt% of the composition is made up of semaglutide, glycerol dioleate, phosphatidyl choline, glycerol and ethanol or a mixture of ethanol and propylene glycol (PG) (the remainder may be additional excipients such as an anti-oxidant and / or stabilizer, etc., and impurities, e.g., impurities from the lipid excipients).[000179] E46. The injectable pharmaceutical composition of any one of El - E45, comprising about 8 wt% - about 12 wt% ethanol and about 5.5 wt% - about 10.5 wt% PG. about 1 wt% - about 5 wt% glycerol and an optional antioxidant or optional additional excipient, and the remainder consisting of phosphatidyl choline and glycerol dioleate is in the range of about 55:45 - about 45:55.[000180] E47. The injectable pharmaceutical composition of any one of El - E45, comprising about 7 wt% - about 15 wt% ethanol, and about 5.5 wt% - about 12.5 wt% PG; about 1 wt% - about 5 wt% glycerol and an optional antioxidant or optional additional excipient, and the remainder consisting of phosphatidyl choline and glycerol dioleate is in the range of about 55:45 - about 45:55.[000181] E48. The injectable pharmaceutical composition of any one of El - E47, wherein the lipid excipients, such as phosphatidyl choline and glycerol dioleate, constitute about 30 wt% to about 90 wt%, such as about 50 wt% to about 88 wt%, such as about 55 wt% to about 87 wt%, such as about 60 wt% to about 85 wt%, such as 65 wt% to about 84 wt%, of the total pharmaceutical composition.[000182] E49. The injectable pharmaceutical composition of any one of El - E48, wherein the lipid excipients, such as phosphatidyl choline and glycerol dioleate, constitute about 50 wt% to about 88 wt%, of the total pharmaceutical composition.[000183] E50. The injectable pharmaceutical composition of any one of El - E48, wherein the lipid excipients, such as phosphatidyl choline and glycerol dioleate, constitute about 60 wt% to about 88 wt% of the total pharmaceutical composition.[000184] E51. The injectable pharmaceutical composition of any one of El - E48, wherein the lipid excipients, such as phosphatidyl choline and glycerol dioleate, constitute about 65 wt% to about 88 wt%, such as about 66 wt% to about 86 wt%, such as about 67 wt% to about 85 wt%, such as about 68 wt% to about 84 wt%, such as about 69 wt% to about 84 wt%. such as about 70 wt% to about 82 wt% of the total pharmaceutical composition.[000185] E51 1. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0. 1-1.0 mL.[000186] E51_2. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.2 mL.[000187] E51_3. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.3 mL.[000188] E51 4. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.4 mL.[000189] E51_5. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.5 mL.[000190] E51_6. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.6 mL.[000191] E51 7. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.7 mL.[000192] E51 8. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.8 mL.[000193] E51 9. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 0.9 mL.[000194] E51 10. The injectable pharmaceutical composition of any one of El - E51, wherein the composition is provided in a dose volume of about 1.0 mL.[000195] E52. The injectable pharmaceutical composition of any one of El - E51 10, for use as a medicament.[000196] E53. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every two to eight weeks, such as once every three to six weeks, such as once every four to six weeks, such as about every four weeks; or as a once- monthly administration; or such as administration once every 25 to 33 days, such as once every 28 ± 5 days.[000197] E54. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every 28 ± 1 days.[000198] E55. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every’ 28 ± 2 days.[000199] E56. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every' 28 ± 3 days.[000200] E57. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every’ 28 ± 4 days.[000201] E58. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every' 28 ± 5 days.[000202] E59. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every' 28 ± 6 days.[000203] E60. The injectable pharmaceutical composition of El - E52, wherein the medicament is for administration once every' 28 ± 7 days.[000204] E61. The injectable pharmaceutical composition of E53 - E60, wherein the administration is subcutaneous injection.[000205] E62. The injectable pharmaceutical composition of any one of El - E61, wherein administration of the composition to a human results in a mean Cmax.ss in the range of about 20 ng / mL (5 nmol / L) to about 1350 ng / rnL (330 nmol / L), such as about 40 - about 1200 ng / mL (10-290 nmol / L), such as about 60 - about 1050 ng / mL (15-255 nmol / L).[000206] E63. The injectable pharmaceutical composition of any one of El - E62, wherein administration of the composition to a human results in a mean Cmax,ss in the range of about 60 - about 1050 ng / mL (15-255 nmol / L).[000207] E64. The injectable pharmaceutical composition of any one of E62 - E63, wherein the human is an adult human.[000208] E65. The injectable pharmaceutical composition of any one of El - E64, for treating a disease, condition, or a symptom thereof is selected from the group consisting of Alzheimer's disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus, obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular disorders, stroke, inflammatory bowel syndrome, dyspepsia, Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder or opioid use disorder.[000209] E65 1. The injectable pharmaceutical composition of E65, wherein the disease, condition, or a symptom thereof is selected from the group consisting of hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, and glycemic control in adults with type 2 diabetes mellitus.[000210] E65 2. The injectable pharmaceutical composition of E65, wherein the disease, condition, or a symptom thereof is selected from the group consisting of substance use disorder such as alcohol use disorder or opioid use disorder.[000211] E65_3. The injectable pharmaceutical composition of E65, wherein the disease, condition, or a symptom thereof is obesity.[000212] E66. A method of treating a disease, condition, or a symptom thereof comprising administering, to a mammalian patient in need thereof a composition according to any one of El - E65_3.[000213] E67. The method of E66. wherein the administration is a parenteral injection, administered once every two to five weeks, such as once every 14 days ± 5 days, such as once every 28 days ± 7 days, such as once every 28 days ± 6 days, such as once every' 28 days ± 5 days, such as once every' 28 days ± 4 days, such as once every' 28 days ± 3 days, such as once every 28 days ± 2 days, such as once every' 28 days ± 1 days such as once every' 28 days.[000214] E68. The method of E66, wherein the administration is a subcutaneous injection, administered once every once every 28 days ± 7 days.[000215] E69. The method of E66, wherein the administration is a subcutaneous injection, administered once every once every 28 days ± 6 days.[000216] E70. The method of E66, wherein the administration is a subcutaneous injection, administered once every once every 28 days ± 5 days.[000217] E71. The method of E66, wherein the administration is a subcutaneous injection, administered once every once every 28 days ± 4 days.[000218] E72. The method of E66, wherein the administration is a subcutaneous injection, administered once every once every 28 days ± 3 days.[000219] E73. The method of E66, wherein the administration is a subcutaneous injection, administered once every once every 28 days ± 2 days.[000220] E74. The method of E66, wherein the administration is a subcutaneous injection, administered once every once every 28 days ± 1 days.[000221] E75. The method of any one of E66 - E74, wherein the composition comprises about 10 mg to about 20 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000222] E76. The method of any one of E66 - E75, wherein the administration provides a mean Cmax.ss in the range of about 20 ng / mL (5 nmol / L) to about 1350 ng / mL (330 nmol / L), such as about 40 to about 1200 ng / mL (10-290 nmol / L). such as about 60 to about 1050 ng / mL (15-255 nmol / L) in the mammalian patient.[000223] E77. The method of any one of E66 - E76, wherein the disease, condition, or a symptom thereof is selected from the group consisting of Alzheimer' s disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus, obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction- associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular disorders, stroke, inflammatory bowel syndrome, dyspepsia. Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder or opioid use disorder.[000224] E78. The method of any one of E66 - E77, wherein the disease, condition, or a symptom thereof is selected from the group consisting of hyperglycemia, type 2 diabetesmellitus, impaired glucose tolerance, type 1 diabetes mellitus, and glycemic control in adults with type 2 diabetes mellitus.[000225] E78_l. The method of any one of E66 - E77, wherein the disease, condition, or a symptom thereof is selected from the group consisting of substance use disorder such as alcohol use disorder or opioid use disorder.[000226] E78_2. The method of any one of E66 - E77. wherein the disease or condition is obesity.[000227] E79. The method of any one of E66 - E78_2, wherein the mammalian patient is a human, such as an adult human.[000228] E80. A method of treating a mammalian patient suffering from a disease, condition or symptom thereof wherein a first dose of the composition of any one of El - E65 is administered to the mammalian patient, and wherein a second dose of the composition of any one of El - E65 is administered after about one to five weeks, such as 1, 2 4 or 4 weeks, of the administration of the first dose, and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the first dose.[000229] E80_l. The method of E80, wherein a second dose of the composition of any one of El - E65 is administered after about one week of the administration of the first dose.[000230] E80_2. The method of E80, wherein a second dose of the composition of any one of E l - E65 is administered after about two weeks of the administration of the first dose.[000231] E80_3. The method of E80, wherein a second dose of the composition of any one of El - E65 is administered after about three weeks of the administration of the first dose.[000232] E80_4. The method of E80, wherein a second dose of the composition of any one of El - E65 is administered after about four weeks of the administration of the first dose.[000233] E81. The method of E80 (i.e., E80 and E80_l - E80_4), wherein the first dose consists of about 0.5 mg to about 5 mg, such as about 1.25 mg to about 4 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000234] E81_l. The method of E81. wherein the first dose consists of about 0.5 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof.[000235] E81_2. The method of E81, wherein the first dose consists of about 0.75 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000236] E81 3. The method of E81, wherein the first dose consists of about 1 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000237] E81 4. The method of E81, wherein the first dose consists of about 1.25 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000238] E81_5. The method of E81, wherein the first dose consists of about 1.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000239] E81 6. The method of E81, wherein the first dose consists of about 1.75 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000240] E81_7. The method of E81, wherein the first dose consists of about 2 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000241] E81_8. The method of E81, wherein the first dose consists of about 2.25 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000242] E81 9. The method of E81. wherein the first dose consists of about 2.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000243] E81_10. The method of E81, wherein the first dose consists of about 2.75 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000244] E81 11. The method of E81, wherein the first dose consists of about 3 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000245] E81_12. The method of E81, wherein the first dose consists of about 3.25 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000246] E81 13. The method of E81, wherein the first dose consists of about 3.5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000247] E81_14. The method of E81, wherein the first dose consists of about 4 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000248] E82. The method of any one of E80 - E81 (i.e., E80 - E80 4 and E81 - E81 14), wherein the second dose comprises about 1.25 mg or 25 mg semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000249] E82 1. The method of E82, wherein the second dose consists of about 2 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000250] E82_2. The method of E82, wherein the second dose consists of about 2.5 mg of semaglutide. or an equivalent amount of a pharmaceutically acceptable salt thereof.[000251] E82 3. The method of E82, wherein the second dose consists of about 3 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000252] E82_4. The method of E82, wherein the second dose consists of about 4 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000253] E82_5. The method of E82, wherein the second dose consists of about 5 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000254] E82_6. The method of E82, wherein the second dose consists of about 6 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000255] E82_7. The method of E82, wherein the second dose consists of about 7 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000256] E82 8. The method of E82, wherein the second dose consists of about 8 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000257] E82_9. The method of E82, wherein the second dose consists of about 9 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000258] E82 10. The method of E82, wherein the second dose consists of about 10 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000259] E82 11. The method of E82, wherein the second dose consists of about 11 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000260] E82_12. The method of E82, wherein the second dose consists of about 12 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000261] E82 13. The method of E82, wherein the second dose consists of about 13 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000262] E82_14. The method of E82, wherein the second dose consists of about 14 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000263] E82 15. The method of E82, wherein the second dose consists of about 15 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000264] E82_16. The method of E82, wherein the second dose consists of about 16 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000265] E82_17. The method of E82, wherein the second dose consists of about 17 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000266] E82_l 8. The method of E82, wherein the second dose consists of about 18 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000267] E82_19. The method of E82, wherein the second dose consists of about 19 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000268] E82_20. The method of E82, wherein the second dose consists of about 20 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000269] E82_21. The method of E82, wherein the second dose consists of about 21 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000270] E82_22. The method of E82, wherein the second dose consists of about 22 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000271] E82_23. The method of E82, wherein the second dose consists of about 23 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000272] E82_24. The method of E82, wherein the second dose consists of about 24 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.[000273] E83. The method of any one of E80 - E82_24 (i.e., E80 - E80_4, E81 - E81 19, and E82 - E82_24), wherein any consecutive dose of semaglutide (i.e., a dose other than the first and the second dose, i.e., a third, a fourth, a fifth, etc. dose of semaglutide). or an equivalent amount of a pharmaceutically acceptable salt thereof is as defined in any of E82 - E82_24.[000274] E84. The method of any one of E80 - E83 (i.e., E80 - E80_4, E81 - E81 19, E82 - E82_24, and E83), wherein the administration is subcutaneous injection.[000275] E85. The method of any one of E80 - E84. wherein the second dose and any consecutive dose of the composition is administered to the mammalian patient by subcutaneous injection two to five weeks, such as 14 days ± 3 days, such as 14 days ± 2 days, such as 14 days ± 1 days, such as 28 days ± 7 days, such as 28 days ± 6 days, such as 28 days ± 5 days, such as 28 days ± 4 days, such as 28 days ± 3 days, such as 28 days ± 2 days, such as 28 days ± 1 days, such as 28 days, after administration of the first dose.[000276] E85_l. The method of E80, wherein a first dose comprising 0.5-5 mg, such as 1 mg, 1.25 mg, 1.5 mg, 2 mg, 2.25 mg or 2.5 mg, of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered to the mammalian patient, and a second dose comprising 0.5-5 mg, such as 1 mg, 1.25 mg, 1.5 mg. 2 mg, 2.25 mg, 2.5 mg, 3 mg, 3.25 mg, 3.5 mg or 4 mg, of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered about 14 ± 3 days after the administration of first dose. [000277] E85_2. The method of E85_l, wherein a third dose comprising 3.5-6 mg, such as 4 mg, 4.5 mg, 5 mg. or 5.5 mg of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered to the mammalian patient about 14 ± 3 days to about 28 ± 7 days after the administration of the second dose, such as 14 ± 2 days to about 28 ± 3 days after the administration of the administration of the second dose.[000278] E85_3. The method of E85_2, wherein a fourth dose comprising about 6 mg - about 12 mg. such as 7 mg. 8 mg, 9 mg. or 10 mg of semaglutide or an equivalent amount of apharmaceutically acceptable salt thereof is administered to the mammalian patient about 28 ± 7 days after the administration of the third dose, such as about 28 ± 3 days after the administration of the third dose.[000279] E85_4. The method of any one of E85_l - E85_3, wherein a maintenance dose comprising about 10 mg - about 20 mg, such as about 10 mg, 15 mg, or 20 mg of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered to the mammalian patient about 28 ± 7 days after the administration of a previous dose, such as about 28 ± 3 days after the administration of a previous dose.[000280] E85_5. The method of any one of E80 - E85 4 or E128 - El 38, wherein the disease, condition, or a symptom thereof is selected from the group consisting of Alzheimer's disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus, obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular disorders, stroke, inflammatory bowel syndrome, dyspepsia, Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder or opioid use disorder.[000281] E85 6. The method of any one of E80 - E85 4 or E128 - E138, wherein the disease, condition, or a symptom thereof is selected from the group consisting of hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, and glycemic control in adults with type 2 diabetes mellitus.[000282] E85_7. The method of any one of E80 - E85_4 or E128 - El 38, wherein the disease, condition, or a symptom thereof is selected from the group consisting of substance use disorder such as alcohol use disorder or opioid use disorder.[000283] E85_8. The method of any one of E80 - E85_4 or E128 - El 38, wherein the disease or condition is obesity.[000284] E86. An injection device comprising a composition according to any one of El - E65.[000285] E87. An injection device for use in a method according to any one of El - E65.[000286] E88. The injection device according to E86 or E87, wherein the device is adapted for subcutaneous administration.[000287] E89. The injection device according to any one of E86 - E88, wherein the device is an automatic administration device.[000288] E90. The injection device according to any one of E86 - E88, wherein the device is selected from the group consisting of a prefilled syringe, prefilled pen and an automatic injection device, such as an auto-injector or pen injector.[000289] E91. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 3 mg / mL - about 25 mg / mL.[000290] E92. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 5 mg / mL - about 20 mg / mL.[000291] E93. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 5 mg / mL.[000292] E94. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 6 mg / mL.[000293] E95. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 7 mg / mL.[000294] E96. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 8 mg / mL.[000295] E97. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 9 mg / mL.[000296] E98. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 10 mg / mL.[000297] E99. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 11 mg / mL.[000298] El 00. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 12 mg / mL.[000299] E101. The composition of any one of El - E65. the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 13 mg / mL.[000300] El 02. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 14 mg / mL.[000301] E103. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 15 mg / mL.[000302] E104. The composition of any one of El - E65. the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 16 mg / mL.[000303] E105. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 17 mg / mL.[000304] El 07. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 18 mg / mL.[000305] E108. The composition of any one of El - E65. the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 19 mg / mL.[000306] El 09. The composition of any one of El - E65, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the concentration of semaglutide is about 20 mg / mL.[000307] E110. The composition of any one of El - E65, E91 - E109, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the composition has a viscosity of about 500 mPa-s or less.[000308] El 11. The composition of El 10, wherein the viscosity is about 50 - about 450 mPa-s.[000309] El 12. The composition of El 10, wherein the viscosity7is about 100 - about 400 mPa-s.[000310] El 13. The composition of El 10, wherein the viscosity is about 150 - about 380 mPa-s.[000311] El 14. The composition of El 10, wherein the viscosity is about 150 - about 350 mPa-s.[000312] El 15. The composition of El 10, wherein the viscosity is about 180 - about 350 mPa s.[000313] El 16. The composition of any one of El - E65, E91 - El 15. the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the composition is a solution.[000314] El 17. The composition of any one of El - E65, E91 - El 16, the method of any one of E66 - E85, or the injection device of any one of E86 - E90, wherein the composition is a clear solution as determined by visual inspection.[000315] E118. The composition of any one of El - E65, E91 - E117, for use as a medicament.[000316] El 19. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 0.5 mg - about 7.5 mg semaglutide or a pharmaceutically acceptable salt thereof.[000317] E119 1. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 0.75 mg semaglutide or a pharmaceutically acceptable salt thereof.[000318] E119_2. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 1 mg semaglutide or a pharmaceutically acceptable salt thereof.[000319] E119 3. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 1.25 mg semaglutide or a pharmaceutically acceptable salt thereof.[000320] E119 4. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 1.5 mg semaglutide or a pharmaceutically acceptable salt thereof.[000321] E119 5. The composition of E118, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 1.75 mg semaglutide or a pharmaceutically acceptable salt thereof.[000322] E119 6. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 2 mg semaglutide or a pharmaceutically acceptable salt thereof.[000323] E119_7. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 2.25 mg semaglutide or a pharmaceutically acceptable salt thereof.[000324] E119 8. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 2.5 mg semaglutide or a pharmaceutically acceptable salt thereof.[000325] E119 9. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 2.75 mg semaglutide or a pharmaceutically acceptable salt thereof.[000326] E119 10. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 3 mg semaglutide or a pharmaceutically acceptable salt thereof.[000327] El l 9 11. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 3.25 mg semaglutide or a pharmaceutically acceptable salt thereof.[000328] El 19 12. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 3.5 mg semaglutide or a pharmaceutically acceptable salt thereof.[000329] E119 13. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 3.75 mg semaglutide or a pharmaceutically acceptable salt thereof.[000330] E119 14. The composition of El 18, comprising administering a first dose of the composition to a mammalian patient in need thereof, wherein the first dose is about 4 mg semaglutide or a pharmaceutically acceptable salt thereof.[000331] El 20. The composition of El 18 or E119_14, comprising administering a second dose of the composition to the mammalian patient in need thereof, wherein the second dose is administered about 14 ± 2 days after the administration of the first dose, and the second dose contains about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the first dose.[000332] E121. The composition of El 20, comprising administering a third dose of the composition to the mammalian patient in need thereof, wherein the third dose is administeredabout 14 ± 2 days after the second dose, and the third dose contains about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose.[000333] E121 1. The composition of E121, comprising administering a fourth dose of the composition to the mammalian patient in need thereof, wherein the fourth dose is administered about 14 ± 2 days or 28 ± 3 days after the third dose, and the fourth dose contains about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose.[000334] E122. The composition of any one of El 18 - E121_l, comprising administering a maintenance dose of the composition to the mammalian patient in need thereof, wherein the maintenance dose a) is administered about 14 ± 2 days after the administration of the first or the second dose; b) is administered about 14 ± 2 days after the administration of the third dose or fourth dose; c) is administered about 28 ± 5 days after the administration of the first, the second, the third or the fourth dose; and the maintenance dose is about 5 mg - about 20 mg, such as about 10 mg or 15 mg semaglutide or a pharmaceutically acceptable salt thereof.[000335] E123. The composition of any one of El 19 - E121 1, wherein the first dose is about 0.75 mg, 1 mg, 1.25 mg, about 2.5 mg, or about 3 mg semaglutide or a pharmaceutically acceptable salt thereof.[000336] E123_l. The composition of any one of El 19 - E121_l, wherein the first dose is about 1.25 mg. about 1.5 mg, or about 2 mg semaglutide or a pharmaceutically acceptable salt thereof.[000337] El 24. The composition of any one of El 20 - El 23, wherein the second dose is about two times greater than the first dose, and / or wherein the third dose is about two times greater than the second dose.[000338] E124 1. The composition of any one of E120 - E123, wherein the second dose is about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg semaglutide or a pharmaceutically acceptable salt thereof.[000339] E125. The composition of any one of E121 - E124_l, wherein the third dose is about 5 mg, about 7.5 mg, about 10 mg, or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.[000340] E126. The composition of any one of E122 - E125, wherein the maintenance dose is about 5 mg, about 10 mg, or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.[000341] E126_l. The composition of any one of E122 - E125, wherein the maintenance dose is about 5 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every' 28 ± 5 days.[000342] E126_2. The composition of any one of E122 - E125. wherein the maintenance dose is about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.[000343] E126_3. The composition of any one of E122 - E125, wherein the maintenance dose is about 15 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.[000344] E127. The composition of El 19, wherein the composition comprising a first dose of 0.5-5 mg, such as 1 mg, 1.25 mg, 1.5 mg, 2 mg, 2.25 mg or 2.5 mg, of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered to the mammalian patient, and a second dose of the composition comprising 0.5-5 mg, such as 1 mg, 1.25 mg, 1.5 mg. 2 mg, 2.25 mg. 2.5 mg, 3 mg, 3.25 mg, 3.5 mg, 4 mg or 5 mg. of semaglutide or an equivalent amount of a pharmaceutically' acceptable salt thereof is administered about 14 ± 3 days after the administration of the first dose.[000345] E127_l. The composition of E127, wherein the second dose or another dose of the composition is administered to the mammalian patient by subcutaneous injection two to five weeks, such as 28 days ± 7 days, such as 28 days ± 6 days, such as 28 days ± 5 days, such as 28 days ± 4 days, such as 28 days ± 3 days, such as 28 days ± 2 days, such as 28 days ± 1 days, such as 28 days, such as 14 days ± 3 days, such as 14 days ± 2 days, such as 14 days ± 1 days after the first dose.[000346] E127_2. The composition of E127_l, wherein the composition comprising a third dose comprising 3.5-6 mg, such as 4 mg, 4.5 mg, 5 mg, or 6 mg of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered to the mammalian patient about 14 ± 3 days to about 28 ± 7 days after the administration of the second dose, such as 14 ± 2 days to about 28 ± 3 days after the second dose.[000347] E127_3. The composition of E127_2, wherein the composition comprising a fourth dose comprising about 6 mg - about 12 mg, such as 7 mg, 8 mg. 9 mg. or 10 mg of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered to the mammalian patient about 28 ± 7 days after the administration of the third dose, such as about 28 ± 3 days after the administration of the third dose.[000348] E127 4. The composition of any one of E127 1 - E127 3, wherein a composition comprising a maintenance dose comprising about 10 mg - about 20 mg, such as about 10 mg, about 15 mg, or about 20 mg of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof is administered to the mammalian patient about 28 ± 7 days after the administration of the previous dose, such as about 28 ± 3 days after the administration of the previous dose.[000349] E127_5. The composition of any one of El 18 - E127_4, for use in treating a disease, condition, or a symptom thereof selected from the group consisting of Alzheimer's disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus. obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary' heart disease and other cardiovascular disorders, stroke, inflammatory’ bowel syndrome, dyspepsia, Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder or opioid use disorder.[000350] E127_6. The composition of any one of El 18 - E127_4, for use in treating a disease, condition, or a symptom thereof is selected from the group consisting of hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, and glycemic control in adults with type 2 diabetes mellitus.[000351] E127_7. The composition of any one of El 18 - E127_4, for use in treating a disease, condition, or a symptom thereof is selected from the group consisting of substance use disorder such as alcohol use disorder or opioid use disorder.[000352] E127 8. The composition of any one of El 18 - E127 4, for use in treating a, wherein the disease or condition is obesity.[000353] E128. A method for treating a mammalian patient suffering from a disease or condition, wherein the method comprises administering a first dose of the composition according to any one of El - E65, E91 - El 17 to the mammalian patient in need thereof, andwherein the first dose is about 0.5 mg - about 5 mg semaglutide or a pharmaceutically acceptable salt thereof.[000354] E128_l. The method for treating a mammalian patient suffering from a disease or condition according to E128, wherein the method comprises administering a second dose of the composition according to any one of El - E65, E91 - El 17, and wherein the second dose is administered about 14 ± 2 days after the administration of the first dose, and the second dose is about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, and the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the first dose, such as two times greater than the first dose.[000355] E129. The method for treating a mammalian patient suffering from a disease or condition according to E128, wherein the method comprises administering a third dose and / or a fourth dose of the composition according to any one of El - E65, E91 - El 17, and wherein the third dose and / or fourth dose is administered about 14 ± 2 days after the administration of the second dose or thirds dose, and the third dose and / or the fourth dose is about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof and the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose or the fourth dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose.[000356] El 30. The method for treating a mammalian patient suffering from a disease or condition according to El 28 or El 29, wherein the method comprises administering a maintenance dose of the composition according to any one of El - E65, E91 - El 17, and wherein the maintenance dose is administered a) about 14 ± 2 days from the administration of the first or the second dose; b) about 14 ± 2 days from the administration of the third dose or fourth dose; or c) about 28 ± 5 days from the administration of the first dose, the second, the third dose or the fourth dose; and the maintenance dose is about 5 mg - about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.[000357] E131. The method of any one of E128 - E130, wherein the first dose is about 0.75 mg, 1 mg, 1.25 mg, about 2.5 mg, or about 3 mg semaglutide or a pharmaceutically acceptable salt thereof.[000358] E131 1. The method of any one of E128 - E130, wherein the first dose is about 1.25 mg, about 1.5 mg, or about 2 mg semaglutide or a pharmaceutically acceptable salt thereof.[000359] El 32. The method of any one of E128 - E130, wherein the second dose is about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, or wherein the second dose is two times greater than the first dose.[000360] E133. The method of any one of E128 - E130, wherein the third dose is about 5 mg, about 7.5 mg, about 10 mg, or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.[000361] E134. The method of any one of E128 - E130, wherein the maintenance dose is about 5 mg, about 10 mg, or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.[000362] E135. The method of any one of E128 - E130, wherein the maintenance dose is about 5 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.[000363] E136. The method of any one of E128 - E130, wherein the maintenance dose is about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.[000364] E137. The method of any one of E128 - E130, wherein the maintenance dose is about 15 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.[000365] E138. The method of any one of E134 - E137. wherein the maintenance dose is administered once every 28 ± 5 days.INCORPORATION BY REFERENCE[000366] All publications, patents, and patent applications mentioned herein, including those items listed above, are hereby incorporated by reference in their entirety for all purposes as if each individual publication, patent, or patent application was specifically and individually incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.EQUIVALENTS[000367] Although the disclosure has been described with reference to embodiments and examples, it should be understood that numerous and various modifications can be made without departing from the spirit of the disclosure. And while specific embodiments of the subject disclosure have been discussed, the above specification is illustrative and notrestrictive. Many variations of the disclosure will become apparent to those skilled in the art upon review of this specification. The full scope of the disclosure should be determined by reference to the claims, along with their full scope of equivalents, and the specification, along with such variations.[000368] Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure.EXAMPLES[000369] Materials[000370] SEM Semaglutide[000371] SPC Soy phosphatidylcholine[000372] GDO Glycerol dioleate[000373] EtOH Ethanol[000374] PG Propylene glycol[000375] NMP N-methylpyrrolidone[000376] WFI Water for injection[000377] DMSO Dimethyl sulfoxide[000378] GLY Glycerol[000379] P20 Polysorbate 20[000380] P80 Polysorbate 80[000381] MEG Meglumine[000382] TRE Trehalose[000383] PEG400 Polyethylene glycol 400[000384] Preparation of formulations[000385] Lipid placebo mixtures were prepared by weighing appropriate amounts of SPC,GDO and solvents into sterilized glass vials. Sealed vials were then placed on a roller mixer by end-over-end rotation at room temperature (RT) until mixed completely into clear homogeneous liquid solution (<24 hours). SEM powder was then added to the respective lipidplacebo formulations in new glass vials. Vials were then sealed and placed on a roller mixer by end-over-end rotation at RT for 72 hours.[000386] Example 1: Evaluation of SEM solubility in lipid formulations[000387] The solubility was assessed by adding SEM to respective lipid placebo mixtures followed by mixing on a roller mixer by end-over-end rotation at RT for 72 hours. After preparation, solubility of SEM was assessed by visual inspection, such as the homogeneity of the formulation examined (see tables 1 and 2).[000388] Table 1. Solubility of SEM in various lipid formulations (all components in wt%)1: formulation is turbid and / or non-homogeneous; 2: formulation is clear and homogeneous[000389] Table 2. Solubility of SEM in various lipid formulations (all components in wt%)1: formulation is turbid and / or non-homogeneous; 2: formulation is clear and homogeneous[000390] Example 2: Evaluation of SEM aggregation in hydrated lipid formulationsApproximately 200 mg of each of the selected homogeneous formulation from Table 1 and Table 2 was injected into 10 mL of PBS buffer (pH 7.4) in separate 10R vials with the use of plastic pipette. The vials were sealed and placed on a shaking table (150 rpm) at 37°C to hydrate. Immediately after injection into PBS buffer all formulations started to harden and after less than 24h formed cohesive lumps of liquid crystalline depots. After 5-7 days of hydration, the liquid crystalline depots were taken out from the vials, dissolved in 5 mL of methanol, and the resulting sample solutions were visually inspected for turbidity (Table 3). A turbid sample is taken as an indication of formation of aggregates of semaglutide. The aggregates could not be dissolved in methanol. Of note, all corresponding placebo formulations, i.e., formulations not containing semaglutide, were clear and homogeneous after dissolution of the corresponding liquid crystalline depots in methanol.Table 3: In-vitro evaluationThis example demonstrates that certain formulations (i.e., those marked as '‘clear and homogeneous” in Table 3) demonstrate less aggregation.[000391] Example 1 shows that SEM has good solubility in many of the lipid placebo formulations tested, and that a drug load of at least 2 wt% feasible. Surprisingly, many of the formulations in Example 1 did not work as expected. Example 2 shows that many of the formulations showed signs indicating peptide aggregation, e.g., turbidity, following depot formation in an aqueous medium. Aggregation is an unwanted and complicating factor and as shown in Examples 1 and 2, certain lipid compositions surprisingly solubilized SEM and reduced the aggregation. Examples 1 and 2 enable a lipid composition comprising semaglutide which may be suitable for administration once every two to eight weeks.[000392] Example 3: Pharmacokinetic rat study[000393] The following lipid formulations containing semaglutide were prepared as described under the general description above:(all components in wt%)[000394] In addition to the lipid formulations S15 and S26, an aqueous formulation of semaglutide was prepared in a phosphate buffer (10 mM phosphate, pH 7.4) additionallycontaining 1.4% (wt / wt) propylene glycol. The semaglutide concentration was 1.34 mg / mL, prepared by dissolving semaglutide directly in the aqueous medium, and the aqueous formulation was used as a comparative formulation (Comp) in the pharmacokinetic rat study. [000395] All formulations were sterile filtered (0.22 pm PVDF filters) before use.[000396] The formulations were administered to Sprague-Dawley rats by subcutaneous injection. The lipid formulations were dosed at 1.6 mg semaglutide / animal whereas the comparative aqueous semaglutide formulation was dosed at 0.5 mg semaglutide / animal. Blood samples (0.25 mL) were extracted into EDTA-treated test tubes at pre-specified time points and the samples were then placed on ice (or at approximately +5 °C) immediately after collection and centrifuged (within 60 minutes) at approximately 1500xg, at 5 °C for 10 min. 100 pL plasma samples were collected and stored directly at -80 °C for later analysis of semaglutide. The semaglutide concentration in the rat plasma samples was determined by LC- MS / MS. The pharmacokinetic profiles are shown in Figure 1 (full profile) and Figure 2 (zoom- in during the first week), showing that a lower maximum plasma concentration (Cmax) and prolonged duration was achieved with the lipid formulations S15 and S26 compared to the aqueous formulation of semaglutide (Comp).[000397] Example 4: Pharmacokinetic study in rat assessing lipid ratios[000398] The following lipid formulations with varying weight ratio of SPC / GDO and containing semaglutide were prepared as described under the general description above:[000399] All formulations were sterile filtered (0.22 pm PVDF filters) before use.[000400] The formulations were administered to Sprague-Dawley rats by subcutaneous injection. The lipid formulations were dosed at 1.6 mg semaglutide / animal. Blood samples (0.25 mL) were extracted into EDTA-treated test tubes at pre-specified time points and the samples were then placed on ice (or at approximately +5 °C) immediately after collection and centrifuged (within 60 minutes) at approximately 1500xg, at 5 °C for 10 min. 100 pL plasma samples were collected and stored directly at -80 °C for later analysis of semaglutide. The semaglutide concentration in the rat plasma samples was determined by LC-MS / MS. Thepharmacokinetic profiles are shown in Figure 3. SPC / GDO weight ratios between 55 / 45 and 40 / 60 provided sustained release of semaglutide beyond 2 weeks whereas the release was faster and with a shorter duration for the formulation comprising an SPC / GDO ratio of 60 / 40. Maximum plasma concentrations (Cmax) are shown in Figure 4 for the respective formulation. SPC / GDO ratios between 40 / 60 and 55 / 45 provided Cmax values which were lower by at least about a factor of 2 than the formulation with SPC / GDO ratio of 60 / 40.[000401] Example 5: Clinical trial[000402] A randomized, open-label, multiple-dose trial assessing the PK, PD, safety and tolerability of subcutaneous (SC) doses of S15 and S26 compared with SC doses of Wegovy in generally healthy participants with overweight or obesity, aged 18 to 55 years (inclusive), and with a BMI of >27 and <39.9 kg / m2. A total of approximately 80 participants enrolled in the trial.[000403] Other trial details include:[000404] The estimated duration of the trial is up to 25 w eeks (Group 1) or 16 weeks (Groups 2 to 5).[000405] Screening period: up to 28 days.[000406] Treatment period: 21 weeks for Group 1 or 12 weeks for Groups 2 to 5.[000407] Post-treatment period: approximately 4 weeks.[000408] The frequency of visits varies depending on the group and range from every week up to every 4 weeks.[000409] Initial nausea and diarrhea are very common AEs, and vomiting is a common AE with semaglutide (Wegovy. 2024). To mitigate such AEs, the semaglutide dose will be gradually increased from an assumed non-therapeutic level to therapeutic levels over several months in the randomized Part A of the trial. In Part B of the trial, 2 different dosing regimens will be investigated.[000410] Part A:[000411] In the first part of the trial (Part A), 48 participants will be randomized to 1 of 3 groups with 16 participants in each group.[000412] Group 1 : SC doses of Wegovy in the abdomen at doses in accordance with the product label:[000413] Day 1 to Day 28: 0.25 mg Wegovy’ once every' week (qlw) for 4 weeks;[000414] Day 29 to Day 56: 0.5 mg Wegovy qlw (once-weekly) for 4 weeks;[000415] Day 57 to Day 84: 1 mg Wegovy qlw for 4 weeks;[000416] Day 85 to Day 112: 1.7 mg Wegovy ql w for 4 weeks;[000417] Day 113 to Day 147: 2.4 mg Wegovy ql w for 5 weeks.[000418] Group 2: SC doses of S26 in the abdomen using the following dosing schedule:[000419] Day 1: 1.25 mg S26 10 mg / mL (semaglutide);[000420] Day 15: 2.5 mg of S26 10 mg / mL (semaglutide);[000421] Day 29: 5 mg of S26 10 mg / mL (semaglutide);[000422] Day 57: 5 mg of S26 10 mg / mL (semaglutide).[000423] Group 3: SC doses of S26 and S15 in the abdomen using the following dosing schedule:[000424] Day 1: 1.25 mg S26 10 mg / mL (semaglutide);[000425] Day 15: 2.5 mg of S26 10 mg / mL (semaglutide);[000426] Day 29: 5 mg of SI 5 20 mg / mL (semaglutide);[000427] Day 57: 5 mg of S15 20 mg / mL (semaglutide).[000428] Part B[000429] In the second part of the trial (Part B), 2 groups with 16 participants in each group are planned to be enrolled. Participants in both groups will receive SC doses of S15 and / or S26 in the abdomen using the following dosing schedules:[000430] Group 4:[000431] Day 1: 2.5 mg of S26 10 mg / mL (semaglutide);[000432] Day 15: 5 mg of S 15 20 mg / mL (semaglutide);[000433] Day 29: 10 mg of SI 5 20 mg / mL (semaglutide);[000434] Day 57: 10 mg of S15 20 mg / mL (semaglutide).[000435] Group 5:[000436] Day 1: 5 mg of S15 20 mg / mL (semaglutide);[000437] Day 15: 10 mg of SI 5 20 mg / mL (semaglutide);[000438] Day 29: 15 mg of S15 20 mg / mL (semaglutide);[000439] Day 57: 15 mg of S15 20 mg / mL (semaglutide).[000440] Treatment Period[000441] Participants will come to the clinical site on Day -1 and stay until the 48-hour blood samples have been collected on Day 3. Eligibility wall be confirmed on Day -1. On Day -1, blood and urine samples will be collected for clinical laboratory' tests (blood only) and drug and alcohol screens, and a urine pregnancy test will be performed for female participants asapplicable. Vital signs and ECG will be recorded. Any AEs and changes in concomitant medications since screening will be recorded.[000442] In Part A of the trial, eligible participants will be randomized to 1 of 3 groups (i.e., Groups 1, 2 or 3), equally allocated in a 1:1:1 ratio.[000443] The participants will be given an SC injection in the abdomen of either Wegovy or S26 on Day 1.[000444] HbAlc and fasting blood glucose will be measured at suitable timepoints.[000445] The participants will be confined at the clinical site on the day before the first and last IMP dose. The participants will stay until blood samples for assessment of semaglutide levels have been collected 48 hours after the injections, or longer at the discretion of the Investigator (e.g., in case of safety concerns).[000446] The participants in Group 1 will be trained for self-administration of Wegovy at home, which will occur on Days 22, 36, 50, 64, 78, 92, 106, 120, and 134. Wegovy will be dispensed at the previous visit and used (or unused) injection pens will be collected and inspected by the clinical site personnel at the next visit. Diaries will be dispensed, reviewed and collected during the treatment period and used for self-reporting of AEs (all participants) and home administration of Wegovy (participants in Group 1). AEs reported by the participants in the diaries will be reported and assessed by the Investigator.[000447] Blood samples for analysis of semaglutide concentrations will be collected during the trial as follows:[000448] Participants in Group 1 (dosed with Wegovy):[000449] Upon first Wegovy dose and at the time points the participants will come back to the clinical site to provide blood samples.[000450] Bi-weekly samples will be collected.[000451] Upon last Wegovy dose the participants are dismissed from the clinical site, but will come back to provide blood samples.[000452] Participants in Groups 2 through 5 (dosed with S15 and / or S26):[000453] Upon first dose and at time points the participants will come back to the clinical site to provide blood samples.[000454] Samples will be collected pre-dose.[000455] Upon last dose the participants are dismissed from the clinical site, but will come back to the clinical site to provide blood samples.[000456] Post-Treatment Period[000457] Following the last IMP administration, the participants will perform an EOT Visit, i.e.. Day 148 for participants in Group 1 (Wegovy) and Day 85 for participants in Groups 2 through 5. A physical examination will be performed, blood and urine samples will be collected for clinical laboratory tests (hematology, coagulation, clinical chemistry, viral serology, urine drug screening, and pregnancy testing). Vital signs, weight, and ECG will be recorded, and a urine pregnancy test will be performed (as applicable).[000458] The participants in Groups 2 through 5 will also provide blood samples for PK assessments on Day 99.[000459] Four weeks after the EOT Visit (Day 176 for participants in Group 1 and Day 113 for participants in Groups 2 to 5), the participants will perform an End of Trial Visit. For participants in Group 1, only information on AEs and concomitant medications will be collected at the End of Trial Visit. For participants in Groups 2 to 5, this visit also includes blood sampling for PK and PD assessments.[000460] Participants who withdraw consent or are withdrawn from the trial early will be asked to undergo the assessments scheduled for the EOT Visit as soon as possible after discontinuation. These participants will also be invited to undergo an End of Trial Visit, approximately 4 w eeks after the EOT Visit.[000461] The initial results of the trial confirmed the safety and tolerability of the subcutaneous (SC) doses of S15 and S26, and compared to the Wegovy group (group 1) the compositions disclosed herein and used in the trial as described above indicated a decreased time to the maintenance dose (compared to Wegovy) while maintaining an acceptable and manageable safety and tolerability' profile. The trial also indicates that the investigated compositions reduced the weight of the patients.

Claims

WHAT IS CLAIMED IS:

1. An injectable pharmaceutical composition comprising from about 1 mg to about 50 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, one or more pharmaceutically acceptable lipid excipients, and one or more solvents selected from the group consisting of ethanol, and propylene glycol, and wherein the composition further comprises 0.5 wt% - 15 wt% glycerol.

2. The injectable pharmaceutical composition of claim 1, wherein the composition comprises about 1.25 mg to about 25 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.

3. The injectable pharmaceutical composition of any one of claims 1-2, wherein the composition comprises about 2.5 mg to about 20 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.

4. The injectable pharmaceutical composition of any one of claims 1-3, wherein the composition comprises about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, about 15 mg or about 20 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.

5. The injectable pharmaceutical composition of claim 1, wherein the composition comprises about 1.25 mg to about 15 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof.

6. The injectable pharmaceutical composition of any one of claims 1-5, wherein the lipid excipients are selected from the group consisting of monoacyl glycerol, diacyl glycerol, triacyl glycerol, sorbitan monooleate, sorbitan dioleate, sorbitan trioleate, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, lysophosphatidyl choline, phosphatidic acid, and fatty acid.

7. The injectable pharmaceutical composition of any one of claims 1-6, wherein the lipid excipients are diacyl glycerol and phosphatidyl choline.

8. The injectable pharmaceutical composition of any one of claims 1-7, wherein the one or more solvents is selected from ethanol or a mixture of ethanol and propylene glycol.

9. The injectable pharmaceutical composition of any one of claims 1-8, wherein the composition contains about 5 wt% - about 15 wt% ethanol, such as about 7 wt% - about 13 wt% ethanol, such as about 8 wt% - about 12 wt% ethanol, such as about 10 wt% ethanol.

10. The injectable pharmaceutical composition of any one of claims 1-9, wherein the composition contains about 5 wt% - about 25 wt% PG, such as about 5 wt% - about 15 wt% PG, such as about 5.5 wt% - about 13 wt% PG, such as about 7.5 wt% - about 12.5 wt% PG, such as about 7.5 wt% - about 10.5 wt% PG, such as about 8.5 wt% PG or about 10 wt% PG.

11. The injectable pharmaceutical composition of any one of claims 1-10, wherein the composition contains about 0.7 wt% - about 12.5 wt% glycerol, such as about 1 wt% - about 10 wt% glycerol, such as about 1 wt% - about 7.5 wt% glycerol, such as about 0.5 wt% - about 5 wt% glycerol, such as about 1 wt% - about 5 wt% glycerol, such as about 1 wt% glycerol, about 2 wt% glycerol, about 3 wt% glycerol, about 4 wt% glycerol, or about 5 wt% glycerol.

12. The injectable pharmaceutical composition of any one of claims 6-11, wherein the ratio of phosphatidyl choline to glycerol dioleate is in the range of about 55:45 - about 40:60, such as about 55:45 - about 45:55, such as about 47:53 - about 53:46, such as about 50:50.

13. The injectable pharmaceutical composition of any one of claims 1-12, wherein at least 95 wt% of the composition is made up of semaglutide or an equivalent amount of a pharmaceutically acceptable salt thereof, glycerol dioleate, phosphatidyl choline, glycerol and ethanol or a mixture of ethanol and propylene glycol (PG).

14. The injectable pharmaceutical composition of any one of claims 1-13, comprising about 2.5 mg, about 5 mg, about 10 mg, about 15 mg or about 20 mg of semaglutide, or an equivalent amount of a pharmaceutically acceptable salt thereof, about 8 wt% - about 12 wt% ethanol and about 7.5 wt% - about 10.5 wt% PG, or about 7 wt% - about 15 wt% ethanol, and about 5.5 wt% - about 12.5 wt% PG; and about 1 wt% - about 5 wt% glycerol and an optional antioxidant or optional additional excipient, and the remainder essentially consisting of phosphatidyl choline and glycerol dioleate is in the range of about 55:45 - about 45:55 (wt% ratio).

15. The injectable pharmaceutical composition of any one of claims 1-14, wherein the lipid excipients, such as phosphatidyl choline and glycerol di oleate, constitute about 30 wt% to about 90 wt%, such as about 50 wt% to about 88 wt%, such as about 55 wt% to about 87 wt%, such as about 60 wt% to about 85 wt%, such as 65 wt% to about 84 wt%, of the total injectable pharmaceutical composition.

16. The inj ectable pharmaceutical composition of any one of claims 1-15, provided in a volume of about 0.1-1.0 mL, such as about 0.25 mL, such as about 0.5 mL, such as about 0.75 mL, such as about 1.0 mL.

17. The injectable pharmaceutical composition of any one of claims 1-16, for use as a medicament.

18. The injectable pharmaceutical composition of claim 17, wherein the medicament is adapted for parenteral administration once every two to eight weeks, such as once every two to six weeks, such as every four to six weeks, such as about every four weeks; or as a once-monthly administration; or administration once every 28 days ± 7 days, such as once every 28 days ± 6 days, such as once every 28 days ± 5 days, such as once every 28 days ± 4 days, such as once every 28 days ± 3 days.

19. The injectable pharmaceutical composition of claim 18, wherein the administration is subcutaneous administration.

20. The injectable pharmaceutical composition of any one of claims 1-19 for use as a medicament.

21. The injectable pharmaceutical composition of any one of claims 1-20, for use in the treatment of a disease or condition selected from the group consisting of Alzheimer's disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus, obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular disorders, stroke, inflammatory bowel syndrome, dyspepsia, Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder or opioid use disorder.

22. The injectable pharmaceutical composition of claim 21, wherein the disease or condition is selected from the group consisting of hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, and glycemic control in adults with type 2 diabetes mellitus.

23. The injectable pharmaceutical composition of claim 21, wherein the disease or condition is selected from the group consisting of substance use disorder such as alcohol use disorder or opioid use disorder.

24. The injectable pharmaceutical composition of claim 21, wherein the disease or condition is obesity or chronic weight management.

25. The injectable pharmaceutical composition of claims 21-24, comprising administering a first dose of the composition to a mammalian patient, wherein the first dose is about 0.5 mg - about 7.5 mg semaglutide or a pharmaceutically acceptable salt thereof.

26. The injectable pharmaceutical composition of claim 25, comprising administering a second dose of the composition to the mammalian patient in need thereof, wherein the second dose isadministered about 14 ± 2 days after the administration of the first dose, and the second dose is about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the first dose.

27. The injectable pharmaceutical composition of claim 26, comprising administering a third dose of the composition to the mammalian patient in need thereof, wherein the third dose is administered about 14 ± 2 days or 28 ± 5 days after the administration of the second dose, and the third dose is about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose.

28. The injectable pharmaceutical composition of claim 27, comprising administering a fourth dose of the composition to the mammalian patient in need thereof, wherein the fourth dose is administered about 14 ± 2 days or 28 ± 5 days after the administration of the third dose, and the fourth dose is about 5 mg - about 12 mg semaglutide or a pharmaceutically acceptable salt thereof and wherein the amount of semaglutide or a pharmaceutically acceptable salt thereof in the fourth dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose.

29. The injectable pharmaceutical composition of claims 26-28, comprising administering a maintenance dose of the composition to the mammalian patient in need thereof, wherein the maintenance dose a) is administered about 14 ± 2 days after the administration of the first or the second dose; b) is administered about 14 ± 2 days or 28 ± 5 days after the administration of the third or fourth dose; or c) about 28 ± 5 days after the first, the second, the third or the fourth dose; and the maintenance dose is about 5 mg - about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.

30. The injectable pharmaceutical composition of claims 25-29, wherein the first dose is about 1.25 mg, about 2.5 mg or about 5 mg semaglutide or a pharmaceutically acceptable salt thereof.

31. The injectable pharmaceutical composition of claims 26-30, wherein the second dose is about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg semaglutide or a pharmaceutically acceptable salt thereof.

32. The injectable pharmaceutical composition of claims 27-31, wherein the third dose and / or the fourth dose is about 5 mg, about 7.5 mg, about 10 mg or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.

33. The injectable pharmaceutical composition of claims 28-32, wherein the maintenance dose is about 5 mg, about 10 mg or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof and administered once every 28 ± 5 days.

34. The injectable pharmaceutical composition of claims 28-32, wherein the maintenance dose is about 5 mg semaglutide or a pharmaceutically acceptable salt thereof and administered once every 28 ± 5 days.

35. The injectable pharmaceutical composition of claims 28-32, wherein the maintenance dose is about 10 mg semaglutide or a pharmaceutically acceptable salt thereof and administered once every 28 ± 5 days.

36. The injectable pharmaceutical composition of claims 28-32, wherein the maintenance dose is about 15 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.

37. A method of treating a disease, condition, or a symptom thereof comprising administering to a mammalian patient in need thereof a pharmaceutical composition of any one of claims 1-19, wherein the disease, condition, or a symptom thereof is selected from the group consisting of Alzheimer's disease, hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1diabetes mellitus, glycemic control in adults with type 2 diabetes mellitus, obesity, chronic weight management, hypertension, obstructive sleep apnea, syndrome X, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease and other cardiovascular disorders, stroke, inflammatory bowel syndrome, dyspepsia, Parkinson's disease, polycystic ovary syndrome, gastric ulcers and substance use disorder such as alcohol use disorder or opioid use disorder.

38. The method of claim 37, wherein the disease, condition, or a symptom thereof is selected from the group consisting of hyperglycemia, type 2 diabetes mellitus, impaired glucose tolerance, type 1 diabetes mellitus, and glycemic control in adults with type 2 diabetes mellitus.

39. The method of claim 37, wherein the disease, condition, or a symptom thereof is selected from the group consisting of substance use disorder such as alcohol use disorder or opioid use disorder.

40. The method of claim 37, wherein the disease or condition is obesity or chronic weight management.

41. The method for treating a mammalian patient according to any one of claims 37-40, wherein the method comprises administering a first dose of the composition according to any one of claims 1-19 to the mammalian patient in need thereof, and wherein the first dose is about 1 mg - about 7.5 mg semaglutide or a pharmaceutically acceptable salt thereof.

42. The method for treating a mammalian patient according to any one of claims 37-41, wherein the method comprises administering a second dose of the composition according to any one of claims 1-19, and wherein the second dose is administered about 14 ± 2 days after the administration of the first dose, and the second dose is about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, and the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the first dose.

43. The method for treating a mammalian patient according to any one of claims 37-42, wherein the method comprises administering a third dose of the composition according to any one of claims 1-19, and wherein the third dose is administered about 14 ± 2 days or 28 ± 5 days after the administration of the second dose, and the third dose is about 1 mg - about 10 mg semaglutide or a pharmaceutically acceptable salt thereof and the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the second dose.

44. The method for treating a mammalian patient according to any one of claims 37-43, wherein the method comprises administering a fourth dose of the composition according to any one of claims 1-19, and wherein the fourth dose is administered about 14 ± 2 days or 28 ± 5 days after the administration of the third dose, and the fourth dose is about 5 mg - about 12 mg semaglutide or a pharmaceutically acceptable salt thereof and the amount of semaglutide or a pharmaceutically acceptable salt thereof in the fourth dose is the same or greater than the amount of semaglutide or a pharmaceutically acceptable salt thereof in the third dose.

45. The method for treating a mammalian patient according to any one of claims 37-44, wherein the method comprises administering a maintenance dose of the composition according to any one of claims 1-19, and wherein the maintenance dose is administered a) about 14 ± 2 days after the administration of the first or second dose; b) about 14 ± 2 days or 28 ± 5 days after the administration of the third or fourth dose; or c) about 28 ± 5 days after the first, the second, the third or the fourth dose; and the maintenance dose is about 5 mg - about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.

46. The method according to any one of claims 40-45, wherein the method comprises administering a first dose of the composition according to any one of claims 1-19, wherein the first dose is about 1 .25 mg, about 2.5 mg or about 5 mg semaglutide or a pharmaceutically acceptable salt thereof.

47. The method according to any one of claims 41-44, wherein the second dose is about 2.5 mg, about 5 mg, about 7.5 mg, or about 10 mg semaglutide or a pharmaceutically acceptable salt thereof.

48. The method according to any one of claims 43-47, wherein the third dose and / or fourth dose is about 5 mg, about 7.5 mg, about 10 mg or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.

49. The method according to any one of claims 45-48, wherein the maintenance dose is about 5 mg, about 10 mg or about 15 mg semaglutide or a pharmaceutically acceptable salt thereof.

50. The method according to any one of claims 45-48, wherein the maintenance dose is about 5 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.

51. The method according to any one of claims 45-48, wherein the maintenance dose is about 10 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.

52. The method according to any one of claims 45-48, wherein the maintenance dose is about 15 mg semaglutide or a pharmaceutically acceptable salt thereof, and administered once every 28 ± 5 days.

53. The method according to any one of claims 45-48, wherein the maintenance dose is administered once every 28 ± 5 days.

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