Pharmaceutical composition for preventing or treating diabetes

Abstract

A pharmaceutical composition of the present invention, comprising a compound represented by chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof in an amount of 7-90 mg with respect to the weight of a free base, can be effectively used for preventing or treating diabetes via daily administration.

Description

[0001] Description of the Invention

[0002]

Title of invention

[0003]

Technical Field

[0004]

Background Art

[0005]

Prior Art Documents

[0006]

Non-patent literature

[0007] (Non-patent literature 1) Nat Rev Mol Cell Biol. 2008;9(3): 193-205. doi:10.1038 / nrm2327

[0008] (Non-patent Document 2) Diabetes Metab Res Rev. 2004;20 Suppl 2:S13-S23. doi:10.1002 / dmrr.528

[0009] (Non-patent literature 3) Lancet. 1992;340(8825):925-929. doi:10.1016 / 0140-6736(92)92814-v

[0010] (Non-patent literature 4) KJ AN 2022 Feb; 34(1):39-50. doi:https: / / doi.org / 10.7475 / kjan.2022.34.1.39

[0011] (Non-patent literature 5) IDF Diabetes Atlas [Internet] (IDF DIABETES ATLAS [Internet]). 10th edition. Brussels: International Diabetes Federation; 2021. PMID: 35914061.

[0012] (Non-patent literature 6) Diabetes Spectr. 2018; 31(3): 254-260.

[0013] (Non-patent literature 7) Xenobiotica. 2017; 47(11): 1015-1026.

[0014] (Non-patent literature 8) Expert Opin Drug MetabToxicol. 2018; 14(12): 1287-1302. (Non-patent literature 9) ClinPharmacol Ther. 2012; 92(l): 29-39. doi: 10.1038 / clpt.2012.4

[0015] (Non-patent literature 10) Lancet. 2012;379(9824): 1403-1411. doi: 10.1016 / S0140-

[0016] 6736(11)61879-5

[0017] (Non-patent Document 11) Diabetes Care. 2013;36 Suppl 2(Suppl 2):S175-S179. doi: 10.2337 / dcS13-2037

[0018] (Non-patent document 12) Diabetes Care. 2013 Feb;36(2):245-50.doi: 10.2337 / dcl2-0872.

[0019]

Contents of the invention

[0020]

Technical Problem

[0021] A pharmaceutical composition is provided, wherein (3S)-3-(4-(3-(l,4-dioxaspiro [4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof is administered at a dosage of 10 mg to 120 mg per day. [Technical Solution] Each description and embodiment disclosed in the present invention can also be applied to other descriptions and embodiments thereof. That is, all combinations of various elements disclosed in the present invention fall within the scope of the present invention. In addition, the scope of the present invention should not be considered to be limited by the specific description described below. The present invention is a pharmaceutical composition for preventing or treating diabetes, comprising a compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, wherein the compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a dosage of 7 mg to 90 mg per day based on the weight of the free base:

[0022] [Chemical Formula I] The compound represented by the above chemical formula I of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof may be administered in a daily dosage of 7 mg to 90 mg based on the weight of the free base form for preventing or treating diabetes, and a pharmaceutical composition containing the dosage may be administered every day to prevent or treat diabetes. In embodiments of the present invention, the free base form may be the free base form of the compound represented by the above chemical formula I, which may be the free base of (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid. The pharmaceutical composition according to the present invention may be administered every day to effectively prevent or treat diabetes, and side effects may be minimized. In embodiments of the present invention, the pharmaceutical composition can be administered once a day to effectively lower blood sugar in a subject whose blood sugar is not sufficiently controlled by exercise and / or diet. In embodiments of the present invention, the pharmaceutical composition can be administered once a day to a subject with diabetes to effectively lower glycated hemoglobin levels, lower fasting blood sugar and / or postprandial blood sugar (e.g., 1-hour postprandial blood sugar or 2-hour postprandial blood sugar), lower glucoalbumin concentrations, improve insulin secretion capacity of the subject, increase fasting insulin and / or postprandial insulin concentrations, improve IGI (insulinogenic index) of a subject administered the pharmaceutical composition, lower insulin resistance and glycemic variability, and improve the function of pancreatic P cells. In embodiments of the present invention, the pharmaceutical composition may have no or substantially no side effects.In embodiments of the present invention, even if the pharmaceutical composition is administered daily, symptoms such as hypoglycemia and anemia do not occur or rarely occur after administration to a subject with diabetes, and liver function and kidney function can be maintained normally. For example, even if the pharmaceutical composition is administered to a subject with diabetes, the levels of AST, ALT, and bilirubin can be maintained normally at substantially similar levels to those before administration of the pharmaceutical composition, and the levels of BUN (Blood Urea Nitrogen), uric acid, creatine, and NAG (N-acetyl-P-D-glucosaminidase) can be maintained normally at substantially similar levels to those before administration of the pharmaceutical composition. In embodiments of the present invention, the pharmaceutical composition can be administered every day without being affected by the characteristics of the subject's sex, age, BMI, or HOMA-P, and can effectively prevent or treat diabetes. For example, the pharmaceutical composition can effectively lower the glycated hemoglobin level of the subject, and can effectively lower the glycoalbumin level, regardless of the characteristics of the sex, age, BMI or HOMA-P of the subject. In embodiments of the present invention, the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is included, and the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in an amount of 9 to 77 mg per day, specifically 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg or 72 to 77 mg, more specifically 9.375 mg, based on the weight of the free base.

[0023] When administered in a dosage of 18.75 mg, 37.5 mg or 75 mg, diabetes can be effectively prevented or treated. In embodiments of the present invention, the pharmaceutical composition comprises a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, and the compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a dosage of 36 to 77 mg per day, specifically 37.5 mg to 75 mg, based on the weight of the free base, to exhibit an excellent blood sugar lowering effect, and can effectively lower glycated hemoglobin, thereby exhibiting a remarkably excellent preventive or therapeutic effect on diabetes, and can minimize side effects even when administered for a long period of time, and may not cause damage to the heart, kidneys, liver, etc. In embodiments of the present invention, the pharmaceutical composition comprises a compound represented by the above chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, and the compound represented by the above chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered at a dose of 36 to 38.5 mg, or 72 to 77 mg, specifically 37.5 mg or 75 mg per day based on the weight of the free base, and exhibits an excellent blood sugar lowering effect, can effectively lower glycated hemoglobin, and exhibits a remarkably excellent preventive or therapeutic effect on diabetes, and can minimize side effects even when administered for a long period of time and may not cause damage to the heart, kidneys, liver, etc. For example, the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in an amount of 36 to 38.5 mg, or 72 to 77 mg, specifically 37 mg, per day based on the weight of the free base.When administered at a dosage of 5 mg or 75 mg, the antidiabetic effect can be maximized while side effects are kept below a certain level. In embodiments of the present invention, the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a daily dosage for preventing or treating diabetes, based on the weight of the free base, of 9 to 77 mg, specifically 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 9.375 mg, 18.75 mg, 37.5 mg, or 75 mg, and a pharmaceutical composition containing the dosage can be administered every day to prevent or treat diabetes. In embodiments of the present invention, the compound represented by the above formula I, its stereoisomer, its pharmaceutically acceptable salt, or its hydrate or solvate is administered in a daily dosage for the prevention or treatment of diabetes of 36 to 77 mg, specifically 37.5 to 75 mg, based on the weight of the free base, and a pharmaceutical composition comprising the dosage is administered every day to exhibit an excellent blood sugar lowering effect and to exhibit a remarkably excellent preventive or therapeutic effect on diabetes, such as being able to effectively lower glycated hemoglobin, and can minimize side effects even when administered for a long period of time and may not cause damage to the heart, kidneys, liver, etc. The compound represented by the above formula I, its stereoisomer, its pharmaceutically acceptable salt, or its hydrate or solvate is administered in a daily dosage for the prevention or treatment of diabetes of 36 to 38.5 mg, or 72 to 77 mg, specifically 37.5 to 75 mg, based on the weight of the free base.5 mg or 75 mg, a pharmaceutical composition comprising the above dosage is administered once a day to exhibit an excellent blood sugar lowering effect, and exhibits a remarkably excellent preventive or therapeutic effect on diabetes, such as being able to effectively lower glycated hemoglobin, and can minimize side effects even when administered for a long period of time, and may not cause damage to the heart, kidney, liver, etc. For example, the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof may be administered once a day in an amount of 36 to 38.5 mg, or 72 to 77 mg, specifically 37.5 mg or 75 mg, based on the weight of the free base, and a pharmaceutical composition comprising the above dosage is administered once a day to maximize the effect of treating diabetes while maintaining side effects below a certain level. In embodiments of the present invention, the pharmaceutical composition may be a pharmaceutical composition that is administered orally to prevent or treat diabetes. For example, the pharmaceutical composition comprises a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, and the compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is orally administered at a dosage of 7 mg to 90 mg (e.g., 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg) per day based on the weight of the free base, thereby effectively preventing or treating diabetes. In embodiments of the present invention, the pharmaceutical composition may be a pharmaceutical composition that is orally administered once a day to prevent or treat diabetes.For example, a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is included, and the compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is orally administered once a day at a dose of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically, 36 to 77 mg, and even more specifically, 36 to 38.5 mg or 72 to 77 mg) based on the weight of the free base, thereby effectively preventing or treating diabetes. In embodiments of the present invention, diabetes is a disease in which blood sugar levels abnormally rise, and may include type 1 diabetes, type 2 diabetes, gestational diabetes, or other diabetes (secondary diabetes) caused by specific causes, such as genetic defects, genetic diseases, drugs, infections, immune mediation, etc. In embodiments of the present invention, diabetes may refer to a case in which blood sugar levels are higher than the normal blood sugar standards of less than 100 mg / dL of plasma glucose after fasting for 8 hours or more and less than 140 mg / dL of plasma glucose after 2 hours of a 75 g oral glucose load. For example, a subject may have diabetes if he or she satisfies one or more of the following criteria:

[0024] 1) Glycated hemoglobin 6.5% or higher

[0025] 2) Plasma glucose of 126 mg / dL or higher after fasting for 8 hours or more

[0026] 3) Plasma glucose ≥200 mg / dL 2 hours after a 75 g oral glucose load, or

[0027] 4) Random plasma glucose of 200 mg / dL or higher with typical symptoms of diabetes (polyuria, polydipsia, unexplained weight loss) In embodiments of the present invention, diabetes may also include pre-diabetes, and if a subject satisfies one or more of the following criteria, the subject may be treated as being in the pre-diabetes stage as being outside the normal range:

[0028] 1) Impaired fasting glucose: Fasting plasma glucose 100-125 mg / dL

[0029] 2) Plasma glucose 140-199 mg / dL 2 hours after a 75 g oral glucose load or

[0030] 3) Glycated hemoglobin: 5.7-6.4% In embodiments of the present invention, the diabetes may be type 2 diabetes. In embodiments of the present invention, the pharmaceutical composition is a composition that can be administered every day to prevent or treat diabetes in a subject, and the subject may be a subject with type 2 diabetes. For example, a pharmaceutical composition comprising 7 mg to 90 mg (specifically 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, even more specifically 36 to 38.5 mg or 72 to 77 mg) of the compound represented by the above formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base, can be orally administered every day to effectively treat type 2 diabetes. In embodiments of the present invention, the pharmaceutical composition is a composition administered every day to prevent or treat diabetes in a subject, wherein the subject may be a subject who has not been administered another antidiabetic agent for more than one month prior to administration of the pharmaceutical composition. In embodiments of the present invention, the pharmaceutical composition is a composition administered every day to prevent or treat diabetes in a subject, wherein the subject may be a subject with diabetes, and the subject may have a glycated hemoglobin (HbAlc) level of more than 5.6% before administration of the pharmaceutical composition, specifically, 5.7% or more, more specifically, 6.5% or more, and even more specifically, 8.5% or more. For example, the subject may have a glycated hemoglobin (HbAlc) level of more than 6.5%, more than 7.0%, more than 7.5%, more than 8.0%, or more than 8.5% before administration of the pharmaceutical composition.In embodiments of the present invention, the pharmaceutical composition is a composition for preventing or treating diabetes in a subject by being administered every day, wherein the subject may be a subject with diabetes, and the subject may have a glycated hemoglobin (HbAlc) level of 6.5% to 11% before administration of the pharmaceutical composition, and specifically, may have a level of 7% to 10%. In embodiments of the present invention, the pharmaceutical composition is a composition for preventing or treating diabetes in a subject by being administered every day, wherein the subject may be a subject suffering from diabetes, and the pharmaceutical composition comprises 7 mg to 90 mg (specifically 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, and even more specifically 36 to 38.5 mg or 72 to 77 mg) of the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base, when orally administered every day, the glycated hemoglobin level of the subject can be lowered to less than 7%. In embodiments of the present invention, the pharmaceutical composition is a composition for preventing or treating diabetes in a subject, and the pharmaceutical composition may be administered to the subject for 4 weeks or more, 8 weeks or more, 10 weeks or more, or 12 weeks or more. For example, the pharmaceutical composition may be administered to the subject for 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks. In embodiments of the present invention, the compound represented by formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in an amount of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, even more specifically 36 to 38.A pharmaceutical composition comprising (5 mg or 72 to 77 mg) can be orally administered to a subject with diabetes once a day for 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks or more to effectively treat diabetes (e.g., type 2 diabetes). In embodiments of the present invention, a pharmaceutical composition comprising a compound represented by formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof in an amount of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, and even more specifically 36 to 38.5 mg or 72 to 77 mg) based on the weight of the free base is orally administered to a subject with diabetes every day for 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks or more, and can effectively lower the level of glycated hemoglobin, and can lower fasting blood sugar and / or postprandial blood sugar (e.g., 1-hour postprandial blood sugar or 2-hour postprandial blood sugar), and can lower the concentration of glycoalbumin. , and can increase the concentration of C-peptide, improve the insulin secretion ability of a subject, and increase the concentration of fasting insulin and / or postprandial insulin. In embodiments of the present invention, the compound represented by formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is present in an amount of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, even more specifically 36 to 38.A pharmaceutical composition comprising 5 mg or 72 to 77 mg) can be orally administered to a subject with diabetes every day for 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks or more, and can reduce HOMA-IR, increase HOMA-P, improve IGI (insulinogenic index), and not cause weight gain, etc. In embodiments of the present invention, a pharmaceutical composition comprising a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof in an amount of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, and even more specifically 36 to 38.5 mg or 72 to 77 mg) based on the weight of the free base can be administered every day for 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks or more without causing or almost without causing symptoms such as hypoglycemia or anemia, and liver function or renal function can be maintained normally. For example, even if the pharmaceutical composition is administered to a subject with diabetes once a day, the levels of AST, ALT, and bilirubin can be maintained normally at substantially similar levels to those before administration of the pharmaceutical composition, and the levels of BUN (Blood Urea Nitrogen), uric acid, creatine, and NAG (N-acetyl-P-D-glucosaminidase) can be maintained normally at substantially similar levels to those before administration of the pharmaceutical composition. The term “pharmaceutically acceptable” of the present invention may mean physiologically acceptable and not typically causing gastrointestinal disorders, allergic reactions such as dizziness, or similar reactions when administered to a subject.In the embodiments of the present invention, the “pharmaceutically acceptable salt” means a salt commonly used in the pharmaceutical industry, and may be a metal salt or an organic acid salt, and specifically, may be an alkali metal salt, an alkaline earth metal salt, or an amino acid salt, and more specifically, a metal salt manufactured with calcium, potassium, sodium, or magnesium; an inorganic acid salt manufactured with hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, iodic acid, perchloric acid, or sulfuric acid; an organic acid salt manufactured with acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, spartic acid, ascorbic acid, carbonic acid, or vanillic acid; Sulfonate made of methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or naphthalenesulfonic acid, etc.; amino acid salt made of glycine, arginine or lysine, etc.; and amine salt made of trimethylamine, triethylamine, ammonia, pyridine or picoline, etc., and the types of salts meant in the present invention are not limited by these listed salts. For example, the “pharmaceutically acceptable salt” may be a sodium salt or a lysine salt of (L)-lysine salt, (D)-lysine salt or (L, D)-lysine salt. In embodiments of the present invention, the pharmaceutically acceptable salt may be a compound represented by the following chemical formula 1-1.

[0031] [Chemical Formula 1-1]

[0032] The “hydrate” of the present invention is a compound represented by the formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and water are bound by non-covalent intermolecular forces, and may contain a stoichiometric or non-stoichiometric amount of water. Specifically, the hydrate may contain water in a ratio of about 0.25 mol to about 10 mol based on 1 mol of the active ingredient, and more specifically, may contain about 0.5 mol, about 1 mol, about 1.5 mol, about 2 mol, about 2.5 mol, about 3 mol, about 5 mol, etc. The “solvate” of the present invention is a compound represented by the formula I, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a solvent other than water are bound by non-covalent intermolecular forces, and may contain the solvent in a stoichiometric or non-stoichiometric amount. Specifically, the above solvate may contain solvent molecules in a ratio of about 0.25 mol to about 10 mol based on 1 mol of the active ingredient, and more specifically, may contain about 0.5 mol, about 1 mol, about 1.5 mol, about 2 mol, about 2.5 mol, about 3 mol, about 5 mol, etc. The present invention is a pharmaceutical composition for preventing or treating diabetes, comprising (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl]benzyloxy)phenyl)hexa-4-inoic acid lysine salt or a stereoisomer thereof, wherein (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hexa-4-inoic acid lysine salt or a stereoisomer thereof is administered at a dosage of 10 mg to 120 mg per day.In embodiments of the present invention, the (3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (lysine salt of a compound represented by Chemical Formula I) may be an (L)-lysine salt of a compound represented by Chemical Formula I, a (D)-lysine salt of a compound represented by Chemical Formula I, an (L, D)-lysine salt of a compound represented by Chemical Formula I, and specifically, a compound represented by Chemical Formula 1-1. The lysine salt of a compound represented by Chemical Formula I of the present invention (for example, a compound represented by Chemical Formula 1-1) or a stereoisomer thereof is administered in a daily dosage of 10 mg to 120 mg for the prevention or treatment of diabetes, and a pharmaceutical composition containing the dosage is administered every day to prevent or treat diabetes. The pharmaceutical composition according to the present invention can be administered once a day to effectively prevent or treat diabetes, and side effects can be minimized. In embodiments of the present invention, the pharmaceutical composition can be administered once a day to effectively lower blood sugar in a subject whose blood sugar is not sufficiently controlled by exercise and / or diet. In embodiments of the present invention, the pharmaceutical composition can be administered once a day to a subject with diabetes to effectively lower glycated hemoglobin levels, lower fasting blood sugar and / or postprandial blood sugar (e.g., blood sugar 1 hour after a meal or blood sugar 2 hours after a meal), lower the concentration of glycoalbumin, improve the insulin secretion ability of the subject, increase the concentration of fasting insulin and / or postprandial insulin, improve the insulinogenic index (IGI) of a subject administered the pharmaceutical composition, lower insulin resistance, and improve the function of pancreatic P cells. In embodiments of the present invention, the pharmaceutical composition may have no or substantially no side effects.In embodiments of the present invention, even if the pharmaceutical composition is administered every day, symptoms such as hypoglycemia and anemia do not occur or rarely occur after administration to a subject with diabetes, and liver function and kidney function can be maintained normally. For example, even if the pharmaceutical composition is administered to a subject with diabetes, the levels of AST, ALT, and bilirubin can be normally maintained at substantially similar levels to those before administration of the pharmaceutical composition, and the levels of BUN (Blood Urea Nitrogen), uric acid, creatine, and NAG (N-acetyl-P-D-glucosaminidase) can be normally maintained at substantially similar levels to those before administration of the pharmaceutical composition. In embodiments of the present invention, the pharmaceutical composition can be administered every day without being affected by the characteristics of the subject's sex, age, BMI, or HOMA-P, and can effectively prevent or treat diabetes. For example, the pharmaceutical composition can effectively lower the glycated hemoglobin level of the subject and can effectively lower the glycoalbumin level regardless of the characteristics of the subject's sex, age, BMI or HOMA-P. In embodiments of the present invention, the pharmaceutical composition comprises a lysine salt of the compound represented by the above formula I (for example, a compound represented by the formula 1-1) or a stereoisomer thereof, and the lysine salt of the compound represented by the above formula I (for example, a compound represented by the formula 1-1) or a stereoisomer thereof is administered at a dose of 12.5 mg to 100 mg, specifically 25 mg to 100 mg, and more specifically 50 mg to 100 mg per day, thereby effectively preventing or treating diabetes.In embodiments of the present invention, the pharmaceutical composition comprises a lysine salt of a compound represented by the chemical formula I (e.g., a compound represented by the chemical formula 1-1) or a stereoisomer thereof, and the lysine salt of a compound represented by the chemical formula I (e.g., a compound represented by the chemical formula 1-1) or a stereoisomer thereof is administered at a dose of 12.5 mg, 25 mg, 50 mg or 100 mg per day, specifically, 50 mg or 100 mg, to effectively prevent or treat diabetes. In embodiments of the present invention, the pharmaceutical composition comprises a lysine salt of a compound represented by the chemical formula I (for example, a compound represented by the chemical formula 1-1) or a stereoisomer thereof, and the lysine salt of the compound represented by the chemical formula I (for example, a compound represented by the chemical formula 1-1) or a stereoisomer thereof is administered at a dose of 50 mg to 100 mg, specifically 50 mg or 100 mg, per day, and exhibits an excellent blood sugar lowering effect, can effectively lower glycated hemoglobin, and exhibits a remarkably excellent preventive or therapeutic effect on diabetes, and can minimize side effects even with long-term administration, and may not cause damage to the heart, kidneys, liver, etc. For example, when the lysine salt of the compound represented by the chemical formula I (for example, a compound represented by the chemical formula 1-1) or a stereoisomer thereof is administered at a dose of 50 mg to 100 mg, specifically 50 mg or 100 mg per day, the side effects can be maintained at a certain level or less, while the diabetes treatment effect can be maximized. In embodiments of the present invention, the lysine salt of the compound represented by the above chemical formula I (for example, the compound represented by the chemical formula 1-1) or a stereoisomer thereof is administered in a daily dose of 12 for the prevention or treatment of diabetes.5 mg to 100 mg, specifically 25 mg to 100 mg, more specifically 50 mg to 100 mg, a pharmaceutical composition comprising the dosage is administered once a day to effectively prevent or treat diabetes. In embodiments of the present invention, the lysine salt of the compound represented by the above formula (I) (for example, the compound represented by the formula 1-1) or a stereoisomer thereof is administered once a day to effectively prevent or treat diabetes at a daily dosage of 12.5 mg, 25 mg, 50 mg or 100 mg, specifically 50 mg or 100 mg, a pharmaceutical composition comprising the dosage is administered once a day to effectively prevent or treat diabetes. In embodiments of the present invention, the lysine salt of the compound represented by the above formula I (for example, the compound represented by the formula 1-1) or a stereoisomer thereof is administered at a daily dosage of 50 mg to 100 mg, specifically 50 mg or 100 mg, for the prevention or treatment of diabetes, and a pharmaceutical composition comprising the dosage is administered every day to exhibit an excellent blood sugar lowering effect and can effectively lower glycated hemoglobin, thereby exhibiting a remarkably excellent preventive or therapeutic effect on diabetes, and can minimize side effects even when administered for a long period of time and may not cause damage to the heart, kidneys, liver, etc. For example, the lysine salt of the compound represented by the above formula I (for example, the compound represented by the formula 1-1) or a stereoisomer thereof is administered at a daily dosage of 50 mg to 100 mg, specifically 50 mg or 100 mg, and a pharmaceutical composition comprising the dosage is administered every day to maximize the effect of treating diabetes while maintaining side effects below a certain level. In embodiments of the present invention, the pharmaceutical composition may be a pharmaceutical composition that is administered orally once a day to prevent or treat diabetes.For example, a lysine salt of a compound represented by the above formula (I) (e.g., a compound represented by the formula 1-1) or a stereoisomer thereof is included, and the lysine salt of a compound represented by the above formula (I) (e.g., a compound represented by the formula 1-1) or a stereoisomer thereof is administered at a dosage of 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg to 100 mg, and even more specifically, 50 mg or 100 mg) per day to effectively prevent or treat diabetes. In embodiments of the present invention, the diabetes may be type 2 diabetes. In embodiments of the present invention, the pharmaceutical composition is a composition that can be administered every day to prevent or treat diabetes in a subject, and the subject may be a subject with type 2 diabetes. For example, the pharmaceutical composition comprises 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically 50 mg to 100 mg, even more specifically 50 mg or 100 mg) of a lysine salt of a compound represented by Chemical Formula I (e.g., a compound represented by Chemical Formula 1-1) or a stereoisomer thereof, and can be orally administered to a subject with type 2 diabetes every day to effectively treat type 2 diabetes. In embodiments of the present invention, the pharmaceutical composition is a composition for preventing or treating diabetes in a subject by being administered every day, and the subject may be a subject who has not been administered another antidiabetic agent for more than 1 month prior to administration of the pharmaceutical composition. In embodiments of the present invention, the pharmaceutical composition is a composition for preventing or treating diabetes in a subject by being administered every day, wherein the subject may be a subject with diabetes, and the subject may have a glycated hemoglobin (HbAlc) level of more than 5.6% before administration of the pharmaceutical composition, specifically, 5.It may be 7% or more, more specifically 6.5% or more, and even more specifically 8.5% or more. For example, the subject may have a glycated hemoglobin (HbAlc) level of 6.5% or more, 7.0% or more, 7.5% or more, 8.0% or more, or 8.5% or more, and specifically 7% or more, before administration of the pharmaceutical composition. In embodiments of the present invention, the pharmaceutical composition is a composition for preventing or treating diabetes in a subject by being administered every day, wherein the subject may be a subject with diabetes, and the subject may have a glycated hemoglobin (HbAlc) level of 6.5% to 11%, and specifically 7% to 10% before administration of the pharmaceutical composition. In embodiments of the present invention, the pharmaceutical composition is a composition that is administered every day to prevent or treat diabetes in a subject, wherein the subject may be a diabetic subject, and the subject is orally administered every day with a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg, or 100 mg, more specifically, 50 mg to 100 mg, and even more specifically, 50 mg or 100 mg) of a lysine salt of a compound represented by Chemical Formula I (for example, a compound represented by Chemical Formula 1-1) or a stereoisomer thereof, so that the glycated hemoglobin level of the subject can be lowered to less than 7%. In embodiments of the present invention, the pharmaceutical composition is a composition that is administered every day to prevent or treat diabetes in a subject, wherein the pharmaceutical composition may be administered to the subject for 4 weeks or more, 8 weeks or more, 10 weeks or more, or 12 weeks or more. For example, the pharmaceutical composition may be administered to the subject for 4 weeks, 6 weeks, 8 weeks, 10 weeks, or 12 weeks.In embodiments of the present invention, 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically,) of a lysine salt of a compound represented by Chemical Formula I (e.g., a compound represented by Chemical Formula 1-1) or a stereoisomer thereof.

[0033] A pharmaceutical composition comprising (50 mg to 100 mg, more specifically 50 mg or 100 mg) can be orally administered to a subject with diabetes once a day for 4 weeks, 6 weeks, 8 weeks, 10 weeks or 12 weeks or more to effectively treat diabetes (e.g., type 2 diabetes). In embodiments of the present invention, a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically 50 mg to 100 mg, even more specifically 50 mg or 100 mg) of a lysine salt of a compound represented by Chemical Formula I (e.g., a compound represented by Chemical Formula 1-1) or a stereoisomer thereof can be orally administered to a subject with diabetes once a day for 4 weeks, 6 weeks, 8 weeks, 10 weeks or 12 weeks or more, to effectively lower glycated hemoglobin levels, lower fasting blood glucose and / or postprandial blood glucose (e.g., 1-hour postprandial blood glucose or 2-hour postprandial blood glucose), lower the concentration of glycoalbumin, improve the insulin secretion ability of the subject, and increase the concentration of fasting insulin and / or postprandial insulin. In embodiments of the present invention, a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically 50 mg to 100 mg, even more specifically 50 mg or 100 mg) of a lysine salt of a compound represented by Chemical Formula I (for example, a compound represented by Chemical Formula 1-1) or a stereoisomer thereof can be orally administered to a subject with diabetes once a day for 4 weeks, 6 weeks, 8 weeks, 10 weeks or 12 weeks or more, and can reduce HOMA-IR, increase HOMA-P, improve IGI (insulinogenic index), and not cause an increase in body weight, etc.In embodiments of the present invention, a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically 50 mg to 100 mg, and even more specifically 50 mg or 100 mg) of a lysine salt of a compound represented by Chemical Formula I (for example, a compound represented by Chemical Formula 1-1) or a stereoisomer thereof can be administered once a day for 4, 6, 8, 10 or 12 weeks or more without causing or hardly causing symptoms such as hypoglycemia or anemia, and normal liver function or renal function can be maintained. For example, even if the pharmaceutical composition is administered to a subject with diabetes every day, the levels of AST, ALT, and bilirubin can be maintained normally at substantially similar levels to those before administration of the pharmaceutical composition, and the levels of BUN (Blood Urea Nitrogen), uric acid, creatine, and NAG (N-acetyl-O-D-ucosaminidase) can be maintained normally at substantially similar levels to those before administration of the pharmaceutical composition. In embodiments of the present invention, the pharmaceutical composition may include one or more pharmaceutically acceptable additives in addition to the compound represented by the chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof (for example, a compound represented by the chemical formula 1-1), or a hydrate or solvate thereof. In embodiments of the present invention, the pharmaceutical composition may be formulated as a preparation for oral administration, and specifically, may be formulated as a solid preparation or a liquid preparation for oral administration.The solid preparation for oral administration may be a tablet, a pill, a powder, a granule, a capsule, a troche, etc., and such a solid preparation may be prepared by mixing the compound of the present invention with at least one pharmaceutically acceptable additive, for example, an excipient such as starch, calcium carbonate, sucrose, lactose, or gelatin, or a lubricant such as magnesium stearate or talc. In addition, the liquid preparation for oral administration may be a suspension, an oral solution, an emulsion, or a syrup, and may include various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. in addition to the diluents commonly used as pharmaceutically acceptable additives, such as water and liquid paraffin. In the embodiments of the present invention, the pharmaceutical composition may be formulated in the form of an oral dosage form and prepared in a unit dose form or prepared by placing it in a multi-dose container. The formulation may be prepared by a conventional method used in formulation in the art or by a method disclosed in Remington's Pharmaceutical Science (19th ed., 1995), and may be formulated into various formulations depending on each disease or ingredient. In embodiments of the present invention, the pharmaceutical composition may be a solid formulation, and specifically, may be a tablet or capsule. According to one example, the pharmaceutical composition is a tablet containing 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, and even more specifically 36 to 38.5 mg or 72 to 77 mg) of a compound represented by formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base, wherein the tablet can be administered once a day to effectively prevent or treat diabetes.According to another example, the pharmaceutical composition is a tablet comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg to 100 mg, even more specifically, 50 mg or 100 mg) of a lysine salt of a compound represented by formula I (e.g., a compound represented by formula 1-1) or a stereoisomer thereof, wherein the tablet is administered once a day to effectively prevent or treat diabetes. In the present invention, “stereoisomers” may include diastereomers and optical isomers, and include a single enantiomer, a mixture of enantiomers including a racemic mixture, a single diastereomer and a mixture of diastereomers, and specifically, the stereoisomers may be optical isomers. In the present invention, “optical isomers” may include a mixture of enantiomers including a single enantiomer and a racemic mixture. These isomers can be separated by resolution using a conventional technique, for example, column chromatography or HPLC. Alternatively, they can be stereospecifically synthesized using optically pure starting materials and / or reagents of a known arrangement. Specifically, the isomers may be optical isomers. In embodiments of the present invention, the stereoisomer of the compound represented by the chemical formula I may be an optical isomer of the compound represented by the chemical formula I. In the present invention, the term “subject” refers to a subject for which a disease must be prevented or treated, and more specifically, may refer to mammals such as humans, monkeys, mice, dogs, cats, horses, and cows, but is not limited thereto.In the present invention, “prevention” may mean any act of inhibiting or delaying the onset of diabetes by administering a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof (e.g., a compound represented by Chemical Formula 1-1 above), or a hydrate or solvate thereof. For example, prevention may mean any act of inhibiting or delaying the onset of diabetes (including pre-diabetes) or symptoms that can be diagnosed as diabetes (including pre-diabetes) by administering a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof (e.g., a compound represented by Chemical Formula 1-1 above), or a hydrate or solvate thereof. The term “treatment” in the present invention refers to any act of improving or beneficially changing the symptoms and suspected symptoms of a subject with diabetes (including pre-diabetes) or diabetes (including pre-diabetes) by administering a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof (e.g., a compound represented by Chemical Formula 1-1 above), or a hydrate or solvate thereof. In embodiments of the present invention, “treatment” may include a case where diabetes (including pre-diabetes) or symptoms related to diabetes (including pre-diabetes) are mildly expressed compared to a case where the compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof (e.g., a compound represented by Chemical Formula 1-1 above), or a hydrate or solvate thereof is not administered. The term “administration” in the present invention refers to introducing a predetermined substance into a subject by an appropriate method. The present invention provides a compound represented by the above chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, which is administered in an amount of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.) per day based on the weight of the free base.A method for preventing or treating diabetes is provided by administering a pharmaceutical composition comprising a compound represented by the above chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, so as to have a dosage of 5 mg or 72 to 77 mg, more specifically 36 to 77 mg, and even more specifically 36 to 38.5 mg or 72 to 77 mg. According to embodiments of the present invention, a method for preventing or treating diabetes is provided by administering a pharmaceutical composition containing 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically, 36 to 77 mg, and even more specifically, 36 to 38.5 mg or 72 to 77 mg) of a compound represented by the above chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base, every day. According to embodiments of the present invention, a method for preventing or treating diabetes (e.g., type 2 diabetes) is provided by administering once a day a pharmaceutical composition comprising 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically, 36 to 77 mg, and even more specifically, 36 to 38.5 mg or 72 to 77 mg) of a compound represented by the above chemical formula I or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base. The present invention relates to a pharmaceutical composition comprising (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof, administered at a dose of 10 mg to 120 mg per day (specifically, 12.The present invention relates to a method for preventing or treating diabetes by administering a pharmaceutical composition comprising the (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (for example, a compound represented by chemical formula 1-1) or a stereoisomer thereof, so as to have a dosage of 5 mg, 25 mg, 50 mg or lOOmg, more specifically 50 mg to lOOmg, and even more specifically 50 mg or lOOmg). According to embodiments of the present invention, the method may be a method for preventing or treating diabetes by administering a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg to 100 mg, even more specifically, 50 mg or 100 mg) of (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (for example, a compound represented by chemical formula 1-1) or a stereoisomer thereof every day. According to embodiments of the present invention, the method may be a method for preventing or treating diabetes (e.g., type 2 diabetes) by administering once a day a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg to 100 mg, even more specifically, 50 mg or 100 mg) of (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof. The present invention provides a pharmaceutical composition comprising a compound represented by the above chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, which is administered in an amount of 7 mg to 90 mg (specifically, 9 to 9.) per day based on the weight of the free base.The present invention relates to the use of a pharmaceutical composition for preventing or treating diabetes by administering a pharmaceutical composition comprising a compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, so as to have a dosage of 625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically 36 to 77 mg, even more specifically 36 to 38.5 mg, or 72 to 77 mg. According to embodiments of the present invention, the use may be a use of a pharmaceutical composition for preventing or treating diabetes by administering a pharmaceutical composition containing 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically, 36 to 77 mg, and even more specifically, 36 to 38.5 mg or 72 to 77 mg) of a compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base, every day. According to embodiments of the present invention, the use may be a use of a pharmaceutical composition for preventing or treating diabetes (e.g., type 2 diabetes) by administering once a day a pharmaceutical composition containing 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically, 36 to 77 mg, and even more specifically, 36 to 38.5 mg or 72 to 77 mg) of the compound represented by the above formula I or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base.The present invention provides a method for preventing or treating diabetes by administering a pharmaceutical composition comprising (3S)-3-(4-(3-(l,4-dioxaspiro [4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof, such that the daily dose is 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg to 100 mg, and even more specifically, 50 mg or 100 mg) of the (3S)-3-(4-(3-(l,4-dioxaspiro [4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof. It relates to a use for treatment. According to embodiments of the present invention, the use is a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg to 100 mg, even more specifically, 50 mg or 100 mg) of (3S)-3-(4-(3-(l,4-dioxaspiro [4, 5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof.

[0034] It may be a use of a pharmaceutical composition for preventing or treating diabetes by administering once a day. According to embodiments of the present invention, the use may be a use of a pharmaceutical composition for preventing or treating diabetes (e.g., type 2 diabetes) by administering once a day a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically 50 mg to 100 mg, even more specifically 50 mg or 100 mg) of (3S)-3-(4-(3-(l,4-dioxaspiro [4, 5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof. The present invention relates to the use of a pharmaceutical composition comprising a compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, in the manufacture of a medicament for preventing or treating diabetes, wherein the pharmaceutical composition is administered in a dose of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically, 36 to 77 mg, and even more specifically, 36 to 38.5 mg or 72 to 77 mg) per day based on the weight of the free base, in the manufacture of a medicament for preventing or treating diabetes. According to embodiments of the present invention, the use is in the manufacture of a medicament for preventing or treating diabetes, wherein the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is used in an amount of 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.The use of the pharmaceutical composition may be to administer the pharmaceutical composition comprising 5 mg or 72 to 77 mg, more specifically 36 to 77 mg, more specifically 36 to 38.5 mg or 72 to 77 mg) every day. According to embodiments of the present invention, the use may be a use of a pharmaceutical composition comprising 7 mg to 90 mg (specifically, 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg, more specifically, 36 to 77 mg, and even more specifically, 36 to 38.5 mg or 72 to 77 mg) of a compound represented by the above formula (I) or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, based on the weight of the free base, administered once a day. The present invention relates to a pharmaceutical composition comprising (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof, in the manufacture of a drug for preventing or treating diabetes, such that the dosage of the (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof is 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg or 100 mg) per day. It relates to the use of a pharmaceutical composition, which is to administer the composition.According to embodiments of the present invention, the use relates to the use of a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg or 100 mg) of (3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl) benzyloxy)phenyl)hex-4-inoic acid lysine salt (for example, a compound represented by chemical formula 1-1) or a stereoisomer thereof, in the manufacture of a medicament for preventing or treating diabetes, wherein the pharmaceutical composition is administered once a day. According to embodiments of the present invention, the use may be a use of a pharmaceutical composition comprising 10 mg to 120 mg (specifically, 12.5 mg, 25 mg, 50 mg or 100 mg, more specifically, 50 mg to 100 mg, even more specifically, 50 mg or 100 mg) of (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof, in the manufacture of a medicament for preventing or treating diabetes (e.g., type 2 diabetes), administered once a day. In the method for preventing or treating diabetes by administering the pharmaceutical composition, the use of the pharmaceutical composition for preventing or treating diabetes, and the use of the pharmaceutical composition for the manufacture of a medicament for preventing or treating diabetes, the diabetes, prevention, and treatment are the same as those described above in the above pharmaceutical composition. The matters described in the pharmaceutical composition may be substantially identically applied to the method for preventing or treating diabetes by administering the pharmaceutical composition, the use of the pharmaceutical composition for preventing or treating diabetes, and the use of the pharmaceutical composition for the manufacture of a medicament for preventing or treating diabetes, unless they are contradictory.

[0035]

Effect of the invention

[0036]

Brief description of the drawing

[0037] This is the result when the compound represented by 1-1 was administered once a day at a dose of 100 mg. Figure 2A is an analysis of covariance with the baseline glycated hemoglobin (HbAlc) value, and for the group administered the compound represented by the chemical formula 1-1 compared to the placebo at weeks 4, 8, and 12, * is p <0.05, ** is p <0.01, and *** is p <0.0()l. Each value in the graph is a value adjusted for the glycated hemoglobin value of each group using the baseline value as a covariate. Figure 2B is a graph showing the change (%) in fasting blood sugar according to the administration of a pharmaceutical composition containing the compound represented by the chemical formula 1-1. The above Figure 2B shows the least squared mean change (%) from the baseline for 12 weeks in fasting blood glucose, which is the main efficacy evaluation variable. 50 mg is the result when the compound represented by Chemical Formula 1-1 was administered once a day at a dose of 50 mg, and 100 mg is the result when the compound represented by Chemical Formula 1-1 was administered once a day at a dose of 100 mg. The above Figure 2B is an analysis of covariance with the baseline fasting blood glucose value. * indicates p <0.05, ** indicates p <0.01, and *** indicates p for the group administered the compound represented by Chemical Formula 1-1 compared to the placebo at weeks 4, 8, and 12. <O.O()l이다. 그래프에서 각 수치는 베이스라인 값을 공변량으로 하여 각 군의 공복혈당 값을 조정한 수치 이다. 도 2C는 화학식 1-1로 표시되는 화합물을 포함하는 약학적 조성물의 투여에 따른 글리코알부민의 변화 (%)를 보여주는 그래프이다.The above Figure 2C is a graph showing the least squared mean change (%) from the baseline for 12 weeks in fasting blood glucose, which is the main efficacy evaluation variable. 50 mg is the result when the compound represented by Chemical Formula 1-1 was administered once a day at a dose of 50 mg, and 100 mg is the result when the compound represented by Chemical Formula 1-1 was administered once a day at a dose of 100 mg. The above Figure 2C is an analysis of covariance with the baseline glycoalbumin value. * indicates p<0.05, ** indicates p<0.01, and *** indicates p for the group administered the compound represented by Chemical Formula 1-1 compared to the placebo at weeks 4, 8, and 12. <O.O()l이다. 그래프에서 각 수치는 베이스라인 값을 공변량으로 하여 각 군의 글리코알부민 값을 조정한 수치 이다. 도 3은 화학식 1-1로 표시되는 화합물을 포함하는 약학적 조성물을 1일 1회로 4주, 8주, 12주 투여 후 당화 혈색소가 7% 미만으로 낮아진 대상체의 비율을 보여주는 그래프로, 50mg은 화학식 1-1로 표시되는 화합물을 50mg의 용량으로 1일 1회 투여하였을 때의 결과이며 , lOOmg은 화학식 1-1로 표시되는 화합물을 lOOmg의 용량으로 1일 1회 투여하였을 때의 결과이다. 상기 도 3에서 4주, 8주 및 12주에서 위 약 대비 화학식 1-1로 표시되는 화합물 투여한 군에 대해 *는 p <0.05, **는 p<0.01, ***는 p<O.O()l이다.

[0038] [Mode for carrying out the invention] Hereinafter, the present invention will be described in detail with examples to help understanding. However, the following examples are only illustrative of the contents of the present invention, and the scope of the present invention is not limited to the following examples. The examples of the present invention are provided to more completely explain the present invention to a person having average knowledge in the art. Through clinical trials, the antidiabetic effect of the compound represented by the following chemical formula 1-1 of the present invention on patients with insufficiently controlled type 2 diabetes mellitus (T2D) was confirmed. [Chemical formula 1-1] The compound represented by the above [Chemical Formula 1-1] is (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid (L) lysine salt. In the above clinical trial, the dosage of 50 mg or 100 mg is based on the weight of (3S)-3-(4-(3-(l,4-dioxaspiro [4, 5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid L-lysine salt (a compound represented by Chemical Formula 1-1). Administration of 50 mg of the compound represented by Chemical Formula 1-1 means administration of 50 mg of (3S)-3-(4-(3-(l,4-dioxaspiro [4, 5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid L-lysine salt, and administration of 100 mg of the compound represented by Chemical Formula 1-1 means administration of (3S)-3-(4-(3-(l,4-dioxaspiro [4, 5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid L-lysine salt. - It means that 100mg of benzyloxy phenyl hexa-4-inoic acid L-lysine salt was administered. Study design: A multi-center, double-blind, randomized, placebo-controlled, parallel-group phase 2 clinical trial was conducted to evaluate the efficacy and safety of the compound represented by chemical formula 1-1 in patients with type 2 diabetes inadequately controlled by diet and exercise. The primary outcome is the change in glycated hemoglobin (HbAlc) at week 12 compared to baseline. Study design and method A double-blind, randomized, placebo-controlled phase 2 clinical trial was conducted to recruit 112 patients with type 2 diabetes aged 18 to 75 years, and the subjects met one of the following conditions:

[0039] - HbAlc level of 7.0% to 10.0% after only diet and exercise for at least 8 weeks before the test

[0040] - If taking one type of oral diabetes medication before the test, the HbAlc level must be 8.5% or less.

[0041] (However, for subjects taking one type of oral diabetes medication, a washout period of at least 8 weeks must be completed, and the HbAlc level must be 7.0% to 10.0% at the start of the placebo administration run preparation period.)

[0042] A parallel-group randomized trial was conducted for 12 weeks of the compound represented by Chemical Formula 1-1 (50 mg and 100 mg groups and placebo group). The primary outcome was the change in glycated hemoglobin (HbAlc) level from baseline to week 12, and the secondary outcomes were the changes in HbAlc, fasting plasma glucose (FPG), postprandial glucose (postprandial ucose), insulin, glycoalbumin, and C-peptide at weeks 4, 8, and 12. Study design This trial was a multicenter, double-blind, randomized, placebo-controlled, parallel-group, phase 2 clinical trial to evaluate the efficacy and safety of the compound represented by Chemical Formula 1-1 for 12 weeks in adults with type 2 diabetes inadequately controlled by diet and exercise. The primary objective of this clinical trial was to evaluate whether the compound represented by chemical formula 1-1 (50 mg and 100 mg) could safely reduce glycated hemoglobin (HbA1c) compared to placebo in adults with type 2 diabetes inadequately controlled by diet and exercise, and to assess changes in glycemic parameters and safety. This study protocol was approved by the Ministry of Food and Drug Safety (Korea) and the institutional review board and was conducted in accordance with the ethical principles of the Declaration of Helsinki and the International Committee for Harmonization of Pharmaceuticals for Human Use Note on Good Clinical Practice. This study was registered with ClinicalTrials.gov (Identifier NCT05666128). Participants met one of the following criteria before screening:

[0043] - Those diagnosed with type 2 diabetes with a glycated hemoglobin (HbAlc) level of 7.0% to 10.0% while undergoing diet and exercise therapy for at least 8 weeks

[0044] - Those diagnosed with type 2 diabetes with an HbAlc level of 8.5% or less and taking one type of oral diabetes medication before the examination

[0045] (However, for subjects who have taken one type of oral diabetes medication, a washout period of at least 8 weeks must be completed, and the placebo administration (Placebo Running) preparation period must begin.

[0046] (HbAlc level should be 7.0% to 10.0%) After consent, participants underwent a run-in period in which they received a placebo for 2 weeks for confirmation. Afterwards, participants were randomly assigned to receive placebo, 50 mg of the compound represented by Chemical Formula 1-1, or 100 mg of the compound represented by Chemical Formula 1-1 for 12 weeks. Efficacy and safety endpoints were assessed at hospital visits. This study was conducted in accordance with the Consolidated Standards of Trial (CONSORT) reporting guidelines. The inclusion criteria for participants were as follows:

[0047] Persons aged 18 to 75 years; Persons who meet the requirements of (i) or (ii) below.

[0048] (i) Type 2 diabetes with a glycated hemoglobin of 7.0% to 10.0% (inclusive) and who have followed a diet and exercise program for at least 8 weeks prior to screening; or

[0049] (ii) Those diagnosed with type 2 diabetes mellitus with an HbAlc level of 8.5% or less while taking one oral antidiabetic agent before the examination (however, in the case of subjects taking one oral antidiabetic agent, they must complete a washout period of at least 8 weeks, and the HbAlc level must be 7.0% to 10.0% at the start of the placebo running run period). However, those who experienced / experienced severe hypoglycemia in the past 3 months, women of childbearing potential with a positive pregnancy test result, and those diagnosed with type 1 diabetes or other immune-mediated diabetes syndromes or with serious complications due to diabetes were excluded from the participants. Participants were enrolled at 11 domestic institutions. After the intervention and baseline assessment screening procedures, a run-in phase was conducted in which subjects who met the inclusion criteria were administered a 2-week placebo. Participants were randomly assigned to 50 mg of the compound represented by Chemical Formula 1-1, 100 mg of the compound represented by Chemical Formula 1-1, or placebo. At screening, glycated hemoglobin levels (<8.5% or >8.5%) served as a stratification factor for randomization. The randomized treatment was administered in capsule form once daily for 12 weeks, and participants were examined at visits every 4 weeks. Outcome Measure Efficacy The primary outcome of this trial was the change from baseline in glycated hemoglobin (HbA1c) levels at week 12. Secondary outcomes included changes from baseline in glycated hemoglobin (HbA1c) at weeks 4 and 8, the proportion of participants with HbA1c levels <7.0%, and changes from baseline in fasting plasma glucose (FPG) and postprandial glucose, insulin, glycoalbumin, and C-peptide at weeks 4, 8, and 12. Oral glucose tolerance tests, which measure blood glucose and insulin, were performed at weeks 4, 8, and 12.Additionally, body weight, glycated hemoglobin / HbA1c ratio, 60 min insulinogenic index (IGI60), homeostasis model assessment of beta-cell function (HOMA-P), homeostasis model assessment of insulin resistance (HOMA-IR), and cluster determinant 36 were evaluated as exploratory endpoints at weeks 4, 8, and 12 compared to baseline. Safety The safety endpoints of the clinical trial according to this example were treatment-emergent adverse events (TEAEs), laboratory tests, physical examinations, vital signs, and 12-lead electrocardiograms (ECGs). TEAEs that occurred from the beginning of the treatment period to the end of the trial (2 weeks after the last dose at week 12) were collected and analyzed. Statistical Analysis In the clinical trials according to the embodiments of the present invention, the intervention was considered effective if the use of the compound represented by Chemical Formula 1-1 (50 mg or 100 mg) was superior to the use of the placebo at a statistical significance of a = 0.05, and if the model was less than or equal to the above value (i.e., p < 0.05). The null hypothesis was that there would be no difference between the compound represented by Chemical Formula 1-1 (50 mg or 100 mg) and the placebo in the change from baseline in mean glycated hemoglobin (HbAlc) at 12 weeks after randomization. The sample size was calculated as the primary outcome. Based on previous clinical trials with other GPR40 agonists, the estimated effect size for the primary outcome derived from these data using the change from baseline in the compound represented by Chemical Formula 1-1 (50 mg or 100 mg) and placebo groups was d = 0.83 (mean 1.0%, SD 1.2%). Additionally, two-way a = 0.05 and power = 80% were assumed.A total sample size of 85 was required for the primary outcome (change in glycated hemoglobin (HbA1c) level at week 12). With an expected dropout rate of 25%, 115 participants were recruited for each group. Continuous variables are presented with descriptive statistics at each time point, and the significance of changes from baseline within groups was tested using a paired t-test. Between-group differences in continuous variables were tested using analysis of variance (ANOVA), while categorical variables were summarized by the number of participants or events and percentages, and the chi-square test was used to test between-group differences. The main analysis of validity and exploratory variables was analysis of variance (ANOVA). Sensitivity and subgroup analyses were performed to test the robustness of the results. Point estimates, 95% confidence intervals (CIs), and two-sided p-values ​​were reported for treatment effects and differences between treatment effects. The main analysis set for evaluating efficacy and exploratory variables was performed using the full analysis set, whereas efficacy and exploratory analyses were assessed using the per-protocol set. All trial participants who received drug, including placebo, were included in the safety analysis, and safety event information was collected. Adverse events (AEs) were coded using MedDRA version 26.1, and all statistical tests were performed two-sided at a significance level of P <0.05 (without multiplicity adjustment). Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc, Cary, NC, USA). Results Baseline characteristics.

[0050] From June 17, 2022, to June 28, 2023, a total of 142 participants were enrolled in the clinical trial, of which 30 were excluded from randomization. The reasons for ineligibility were 5 cases of withdrawal of consent, 24 cases of failure to meet inclusion / exclusion criteria, and 1 case of adverse reaction. Therefore, 112 enrolled participants were randomly assigned, of which 37 were assigned to the placebo group, and 31 and 44 cases were assigned to the 50 mg and 100 mg groups of the compound represented by chemical formula 1-1, respectively, as shown in Figure 1. The overall demographic and baseline characteristics of the participants were similar across the three groups and are shown in Table 1. The mean age and BMI of the participants in the three groups were 56.7–61.7 years and 25.0–26.5 kg / m, respectively. 2 was. The mean duration of disease and mean glycated hemoglobin (HbAlc) after diagnosis of type 2 diabetes were 6.56 years and 7.55% in the 50 mg group of the compound represented by Chemical Formula 1-1, 7.54 years and 7.77% in the 100 mg group of the compound represented by Chemical Formula 1-1, and 6.42 years and 7.85% in the placebo group. In the placebo group, 4 people withdrew consent after randomization. In the 100 mg group of the compound represented by Chemical Formula 1-1, 3 people withdrew consent, and 1 person stopped taking the drug after randomization.

[0051] [Table 1] Demographic and baseline characteristics Validity results

[0052] Regarding the primary endpoint {{o}}, compared to the placebo group, the groups administered 50 mg of the compound represented by Chemical Formula 1-1 and 100 mg of the compound represented by Chemical Formula 1-1 showed statistically significant decreases in glycated hemoglobin (HbAlc) levels at week 12 by -0.73 (95% CI -1.11 to -0.35, p= 0.0002) and -0.85 (95% CI -1.21 to -0.50, p <0.0001), respectively, and the results are shown in Table 2 and Figures 2A to 2C.

[0053] [Table 2] Meanwhile, the group administered 50 mg of the compound represented by Chemical Formula 1-1 had a change in glycated hemoglobin compared to the placebo at week 8 of -0.44 (95% CI -0.74—0.14, p= 0.0049), and the group administered 100 mg of the compound represented by Chemical Formula 1-1 had a change in glycated hemoglobin compared to the placebo at week 8 of -0.55 (95% CI -0.83 to -0.27, p= 0.0002), as shown in Table 3 below.

[0054] [Table 3] Note: Data are mean standard deviations unless otherwise stated. Least squares means and confidence intervals are based on Analysis of Variance. Missing values ​​are the last observation carried forward. Additionally, the least squared mean change in HbAlc compared to the placebo at week 4 was -0.23 (95% CI -0.41 to 0.05, p = 0.0113) in the group administered 100 mg, and the HbAlc level also decreased by 0.19 in the group administered 50 mg (95% CI -0.38 to 0.00, p = 0.0517). The proportion of people who reached a glycated hemoglobin level of less than 7.0% (53 mmol / mol) was significantly higher in the group administered 50 mg of the compound represented by Chemical Formula 1-1 at week 12 (n= 19 of 31 participants, 61.29%, p = 0.0075) and the group administered 100 mg (n= 20 of 42 participants, 47.62%, p = 0.0879) compared to the placebo group (n= 10 of 35 participants, 28.57%). In addition, the proportion of people who reached a glycated hemoglobin level of less than 7.0% (53 mmol / mol) in the group administered 50 mg of the compound represented by Chemical Formula 1-1 and the group administered 100 mg at weeks 4 and 8 also significantly increased compared to the placebo group (Fig. 3). In the above figure 3, for the group administered the compound represented by Chemical Formula 1-1 compared to the placebo at 4, 8, and 12 weeks, * indicates p<0.05, ** indicates p<0.01, and *** indicates p<0.0()l.

[0055] At week 12, along with the decrease in HbAlc levels, FPG levels significantly decreased to 22.6 mg / dL in the 50 mg group and 27.7 mg / dL in the 100 mg group (both Ps <0.05, Table 2). Glycoalbumin levels also decreased by 2.6 and 0.61 in both groups, respectively (both Ps <0.05, Table 2). At week 4, FPG and glycoalbumin levels significantly decreased in both groups (both Ps <0.05, Table 4), and the decreases were statistically significant compared to placebo when baseline was considered as a covariate (Figures 2A and 2B).

[0056] [Table 4] Regarding insulin secretion function, both the 50 mg and 100 mg groups showed significant decreases in postprandial glucose (1 hour, 2 hours) and HOMA-P levels compared to baseline at week 12 (all Ps <0.05, Table 2), and insulin (fasting), C-peptide, HOMA-IR, and glycoalbumin / HbAlc were as described in Tables 2 and 5 (Tables 2 and 5).

[0057] [Table 5] IGI values ​​significantly improved in the lOOmg group at week 12 (1.91, 95% CI 0.34 - 3.48, p = 0.0175). In addition, 1-hour insulin values ​​increased by 12.8 in the lOOmg group (p = 0.0467), and 2-hour insulin values ​​increased by 13.1 in the 50mg group (p = 0.0401).

[0058] In subgroup analyses for glycated hemoglobin and glycoalbumin at week 12, no significant p-interactions were observed between treatment groups with respect to sex, age, BMI, or HOMA-P (Table 6).

[0059] [Table 6] Safety results showed that no serious adverse drug reactions or deaths occurred. In patients with type 2 diabetes mellitus, 50 mg, 100 mg, and placebo were administered. Thirty-five treatment-emergent adverse events (TEAEs) occurred in 22 patients (20.0%) (Table 7).

[0060] [Table of Contents In the group administered 50 mg of the compound represented by Chemical Formula 1-1, a total of 20.0% experienced 10 TEAEs (mild, 9 cases; moderate, 0 cases; severe, 1 case), in the group administered 100 mg of the compound represented by Chemical Formula 1-1, 18.6% experienced 12 TEAEs (mild, 8 cases; moderate, 4 cases; severe, 1 case), and in the placebo group, 12 TEAEs (mild, 8 cases; moderate, 4 cases; severe, 0 cases). In the group administered 50 mg of the compound represented by Chemical Formula 1-1, a total of 9.7% reported 6 unusual adverse events (AESIs), in the group administered 100 mg of the compound represented by Chemical Formula 1-1, 4.7% experienced 2 AESIs, and in the group administered 100 mg of the compound represented by Chemical Formula 1-1, 2.8% experienced 1 AESI. Adverse drug reactions (AESIs) included symptoms such as inflammation, thyroiditis, and colitis, but none of these were causally related to the drug. There were no cases of hypoglycemia among patients who experienced AESIs. No clinically significant changes or findings were observed in clinical laboratory evaluations such as liver function tests, vital sign assessments, 12-lead electrocardiograms, and physical examinations. Some of the related results are listed in Table 8 (liver function tests) and Table 9 (renal function tests).

[0061] [Table 8]

[0062] [Table 9] In the above clinical trial, when the compound represented by Chemical Formula 1-1 was administered orally once a day for 12 weeks at a dose of 50 mg or 100 mg, the glycemic control of patients with type 2 diabetes was significantly improved. When the compound represented by Chemical Formula 1-1 was administered at a dose of 50 mg or 100 mg, the glycated hemoglobin (HbAlc) was - in the 12th week compared to the placebo group, respectively.

[0063] 0.74%, -0.85%, respectively, compared to baseline. Specifically, according to the study results on FPG-o-glycoalbumin, a blood glucose lowering effect was observed at the 4th week at a dose of 50 mg or 100 mg of the compound represented by Chemical Formula 1-1, indicating that the compound represented by Chemical Formula 1-1 exhibits a rapid and potent blood glucose lowering effect at the above dose. In addition, compared to the placebo, the compound represented by Chemical Formula 1-1 exhibited an excellent blood glucose lowering effect in all patients with various characteristics such as gender, age, BMI, and HOMA-P at a dose of 50 mg or 100 mg. In addition, the group administered 100 mg of the compound represented by Chemical Formula 1-1 showed a significant improvement in IGI compared to the placebo group after 12 weeks of administration, indicating that P cell function and insulin secretion function were enhanced. Furthermore, the group administered 50 mg and 100 mg of the compound represented by Chemical Formula 1-1 did not experience hypoglycemia during the 12-week trial, despite enhanced P cell function and insulin secretion. The group administered 50 mg or 100 mg of the compound represented by Chemical Formula 1-1 had a safety and tolerability profile similar to that of the placebo group. Specifically, the group administered 50 mg or 100 mg of the compound represented by Chemical Formula 1-1 showed a favorable safety profile with respect to hepatotoxicity, and the levels of AST, ALT, and bilirubin were substantially similar to those of the placebo group. In addition, the group administered 50 mg or 100 mg of the compound represented by Chemical Formula 1-1 showed a favorable safety profile with respect to renal function, and the levels of blood urea nitrogen, uric acid, creatinine, and NAG were substantially similar to those of the placebo group.Therefore, through the above experiment, the dose of 50 mg or 100 mg of the compound represented by Chemical Formula 1-1 showed excellent blood sugar-lowering effects, glycated hemoglobin-lowering effects, and insulin secretion-promoting effects in patients with type 2 diabetes regardless of gender, age, BMI, and HOMA-P, but could minimize side effects such as hypoglycemia induction, and also showed an excellent safety profile in liver and kidney functions. Embodiment Example 1. A pharmaceutical composition for preventing or treating diabetes, comprising a compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, wherein the compound represented by Chemical Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered at a dose of 7 mg to 90 mg per day based on the weight of the free base. Embodiment 2. In embodiment 1, the pharmaceutical composition is a pharmaceutical composition wherein the compound represented by the formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a dosage of 9 to 77 mg per day based on the weight of the free base. Embodiment 3. In embodiment 1 or 2, the pharmaceutical composition is a pharmaceutical composition wherein the compound represented by the formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a dosage of 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg per day based on the weight of the free base.Embodiment 4 In any one of Embodiments 1 to 3, the pharmaceutical composition comprises a compound represented by Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, administered in a dose of 36 to 77 mg per day based on the weight of the free base. Embodiment 5. In any one of Embodiments 1 to 4, the pharmaceutical composition comprises a compound represented by Formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, administered in a dose of 36 to 38.5 mg or 72 to 77 mg per day based on the weight of the free base. Embodiment 6 In any one of Embodiments 1 to 5, the pharmaceutical composition is administered orally. Embodiment 7. The pharmaceutical composition according to any one of embodiments 1 to 6, wherein the pharmaceutical composition is administered orally once a day. Embodiment 8. The pharmaceutical composition according to any one of embodiments 1 to 7, wherein the diabetes is type 2 diabetes. Embodiment 9 The pharmaceutical composition according to any one of embodiments 1 to 8, wherein the pharmaceutical composition is administered for 4 weeks or more. Embodiment 10. The pharmaceutical composition according to any one of embodiments 1 to 9, wherein the pharmaceutical composition is administered for 8 weeks or more. Embodiment 11. The pharmaceutical composition according to any one of embodiments 1 to 10, wherein the pharmaceutical composition is administered for 12 weeks or more. Embodiment 12. The pharmaceutical composition according to any one of embodiments 1 to 11, wherein the pharmaceutically acceptable salt is a metal salt or an organic acid salt. Embodiment 13. A pharmaceutical composition according to any one of Embodiments 1 to 12, wherein the pharmaceutically acceptable salt is a sodium salt of the compound represented by the chemical formula I. Embodiment 14.A pharmaceutical composition according to any one of embodiments 1 to 12, wherein the pharmaceutically acceptable salt is a lysine salt of a compound represented by the formula (I). Embodiment 15. A pharmaceutical composition according to any one of embodiments 1 to 12 and 14, wherein the pharmaceutically acceptable salt is a compound represented by the formula (1-1). Embodiment 16. A pharmaceutical composition comprising (3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by the formula (1-1)) or a stereoisomer thereof, for preventing or treating diabetes.

[0064] A pharmaceutical composition wherein the (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (e.g., a compound represented by chemical formula 1-1) or a stereoisomer thereof is administered at a dose of 10 mg to 120 mg per day. Embodiment 17. A pharmaceutical composition according to embodiment 16, wherein the (3s)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof is administered at a dose of 12.5 mg to 100 mg per day. Embodiment 18. A pharmaceutical composition according to Embodiment 16 or 17, wherein the (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof is administered at a dose of 12.5 mg, 25 mg, 50 mg or 100 mg per day. Embodiment 19. A pharmaceutical composition according to any one of Embodiments 16 to 18, wherein the (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof is administered at a dose of 50 mg to 100 mg per day. Embodiment 20. The pharmaceutical composition according to any one of embodiments 16 to 19, wherein the pharmaceutical composition is for oral administration. Embodiment 21. The pharmaceutical composition according to any one of embodiments 16 to 20, wherein the pharmaceutical composition is for oral administration once a day. Embodiment 22. The pharmaceutical composition according to any one of embodiments 16 to 21, wherein the diabetes is type 2 diabetes. Embodiment 23. The pharmaceutical composition according to any one of embodiments 16 to 22, wherein the pharmaceutical composition is administered for 4 weeks or more.Embodiment 24 A pharmaceutical composition according to any one of embodiments 16 to 23, wherein the pharmaceutical composition is administered for 8 weeks or more. Embodiment 25. A pharmaceutical composition according to any one of embodiments 16 to 24, wherein the pharmaceutical composition is administered for 12 weeks or more. Embodiment 26 A pharmaceutical composition according to any one of embodiments 16 to 25, wherein the (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt is a compound represented by the above chemical formula 1-1. Embodiment 27. A pharmaceutical composition according to any one of embodiments 1 to 26, wherein the pharmaceutical composition is a solid preparation. Embodiment 28. A pharmaceutical composition according to embodiment 27, wherein the solid preparation is a tablet or a capsule. Embodiment 29. A method or use for preventing or treating diabetes by administering a pharmaceutical composition according to any one of embodiments 1 to 28. Embodiment 30. A use for preventing or treating diabetes by administering a pharmaceutical composition according to any one of embodiments 1 to 28 in the manufacture of a medicament for preventing or treating diabetes. Embodiment 31. A method for preventing or treating diabetes by administering a compound represented by the above formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof at a dose of 7 mg to 90 mg per day based on the weight of the free base. Implementation example 32. A method for preventing or treating diabetes by administering (3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (for example, a compound represented by chemical formula 1-1) or a stereoisomer thereof at a dose of 10 mg to 120 mg per day.Embodiment 33 Use of a pharmaceutical composition for preventing or treating diabetes by administering a pharmaceutical composition comprising a compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, in a dosage of 7 mg to 90 mg per day based on the weight of the free base. Embodiment 34 (3)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (for example, a compound represented by chemical formula 1-1) or a stereoisomer thereof, wherein the dosage is 10 mg to 120 mg per day, and a pharmaceutical composition comprising the (3S)-3-(4-(3-(l,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof is administered for the purpose of preventing or treating diabetes. Embodiment 35. Use of a pharmaceutical composition comprising a compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, in the manufacture of a medicament for preventing or treating diabetes, wherein the pharmaceutical composition is administered in a dosage of 7 mg to 90 mg per day based on the weight of the free base of the compound represented by the above formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof.Embodiment 36. Use of a pharmaceutical composition comprising (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt (for example, a compound represented by chemical formula 1-1) or a stereoisomer thereof, in the manufacture of a medicament for preventing or treating diabetes, so that the dosage of the (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof is 10 mg to 120 mg per day.

Claims

【Scope of Claims】 【 Claim 11 A pharmaceutical composition for preventing or treating diabetes, comprising a compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, wherein the compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered at a dose of 7 mg to 90 mg per day based on the weight of the free base: [Chemical Formula I] 【

2. In claim 1, the pharmaceutical composition is a pharmaceutical composition in which the compound represented by the chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a dosage of 9 to 77 mg per day based on the weight of the free base.

3. 73 In claim 1, the pharmaceutical composition is a pharmaceutical composition in which the compound represented by the chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a dosage of 9 to 9.625 mg, 18 to 19.25 mg, 36 to 38.5 mg, or 72 to 77 mg per day based on the weight of the free base.

4. A pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises a compound represented by the chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, administered in a dosage of 36 to 77 mg per day based on the weight of the free base. 【

5. In claim 1, the pharmaceutical composition is a pharmaceutical composition in which the compound represented by the chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is administered in a dosage of 36 to 38.5 mg or 72 to 77 mg per day based on the weight of the free base. 【

6. A pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is administered orally. 【 The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is administered orally once a day.

8. 74 The pharmaceutical composition according to claim 1, wherein the diabetes is type 2 diabetes. 【This claim 1, wherein the pharmaceutical composition is administered for 4 weeks or more, the pharmaceutical composition. 【Claim 1 is claim 1, wherein the pharmaceutical composition is administered for 8 weeks or more, the pharmaceutical composition.

11. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is administered for 12 weeks or more.

12. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt is a metal salt or an organic acid salt.

13. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt is the sodium salt of the compound represented by Formula I.

14. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt is the lysine salt of the compound represented by Formula I.

15. 75 The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt is a compound represented by the following Formula 1-1: [Chemical Formula 1-1]

16. ((The pharmaceutical composition for preventing or treating diabetes, comprising (S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-enoic acid lysine salt or a stereoisomer thereof, of (S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-enoic acid lysine salt or a stereoisomer thereof is administered at a dose of 10 mg to 120 mg per day. ((The pharmaceutical composition according to claim 16, wherein (S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-enoic acid lysine salt or a stereoisomer thereof is administered at a dose of 12.5 mg to 100 mg per day. 【This claim 16, wherein (S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-enoic acid lysine salt or a stereoisomer thereof is administered at a dose of 12.5 mg to 100 mg per day. It should be noted that there are some inaccuracies or unclear parts in the original text, such as "다이옥사스파이로[生이데스-入엔-으- 일서벤질옥시서페닐서헥스-牛이노익산 라이신염" which seems to be incorrect or misspelled chemical terms. The translation is done based on the best understanding of the original text with these potential issues.

18. According to claim 16, the (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8- yl)benzyloxy)phenyl)hex-4-enoic acid lysine salt or a stereoisomer thereof is administered at a dose of 12.5 mg, 25 mg, 50 mg or 100 mg per day, a pharmaceutical composition.

19. According to claim 16, the (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-enoic acid lysine salt or a stereoisomer thereof is administered at a dose of 50 mg to 100 mg per day, a pharmaceutical composition.

20. According to claim 16, the pharmaceutical composition is for oral administration, a pharmaceutical composition. 【 Claim 21 According to claim 16, the pharmaceutical composition is for once-daily oral administration, a pharmaceutical composition. 【 Claim 22 According to claim 16, the diabetes is type 2 diabetes, a pharmaceutical composition. 【 Claim 23 According to claim 16, the pharmaceutical composition is administered for 4 weeks or longer, a pharmaceutical composition.

24. According to claim 16, the pharmaceutical composition is administered for 8 weeks or longer, a pharmaceutical composition. 77

25. According to claim 16, the pharmaceutical composition is administered for 12 weeks or longer, a pharmaceutical composition. 【 Claim 26 According to claim 16, the (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-enoic acid lysine salt is a compound represented by the following Chemical Formula 1-1, a pharmaceutical composition: [Chemical Formula 1-1]

27. According to claim 1 or claim 16, the pharmaceutical composition is a solid preparation, a pharmaceutical composition. 【 Claim 28 According to claim 27, the solid preparation is a tablet or a capsule, a pharmaceutical composition. 【 Claim 29 A compound represented by the following Chemical Formula I, a stereoisomer thereof, their pharmaceutically A method for preventing or treating diabetes, comprising administering an acceptable salt, or a hydrate or solvate thereof, at a dose of 7 mg to 90 mg per day based on the weight of the free base: [Chemical Formula I]

30. A method for preventing or treating diabetes by administering (3S)-3-(4-(3-(l,4-dioxaspiro [4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof at a dose of 10 mg to 120 mg per day.

31. Use of a pharmaceutical composition for preventing or treating diabetes by administering a pharmaceutical composition comprising a compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, in a dosage of 7 mg to 90 mg per day based on the weight of the free base: [Chemical Formula I]

32. A use for preventing or treating diabetes by administering a pharmaceutical composition comprising (3S)-3-(4-(3-(l,4-dioxaspiro [4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof, such that the dosage of (3S)-3-(4-(3-(l,4-dioxaspiro [4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof is 10 mg to 120 mg per day.

33. A pharmaceutical composition for the manufacture of a drug for preventing or treating diabetes, wherein the pharmaceutical composition comprises a compound represented by the following chemical formula I, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, and is administered in a dosage of 7 mg to 90 mg per day based on the weight of the free base: [Chemical Formula I]

34. A use of a pharmaceutical composition comprising (3S)-3-(4-(3-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)benzyloxy)phenyl)hex-4-inoic acid lysine salt or a stereoisomer thereof, in the manufacture of a drug for preventing or treating diabetes, wherein the pharmaceutical composition is administered in a dosage of 10 mg to 120 mg per day.

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