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Use of GLP-1 compound for treatment of critically ill patients

a technology of glp-1 and compound, which is applied in the direction of biocide, plant growth regulator, animal/human protein, etc., can solve the problems of difficulty in rehabilitation, and inability to detect clinical signs, so as to reduce the incidence of critical illness, prevent or reduce the likelihood of a patient suffering, and prolong the time free of critical illness

Inactive Publication Date: 2006-10-12
KNUDSEN LOTTE BJERRE +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention relates to a method for preventing and treating critical illness and related complications in patients. The invention involves controlling glucose metabolism by using a GLP-1 compound to clamp blood glucose levels within a range. This can be done by keeping the blood glucose level below a certain threshold or above another threshold. The invention aims to reduce the risk of critical illness and death in patients, as well as to improve survival and reduce hospitalization duration and the need for mechanical ventilatory support. It also aims to prevent and treat sepsis, bacteraemia, septic shock, and other infectious diseases. Overall, the invention provides a treatment that can prevent, treat, and even cure critical illness and related complications in patients."

Problems solved by technology

However, clinical signs are often absent and it remains an acute problem in many ICUs worldwide.
Nonetheless, it is an important clinical entity as it is a frequent cause of difficulty in weaning patients from the ventilator and it leads to problems with rehabilitation after the acute illness has been treated and cured.
When CIPNP is severe enough, it causes limb weakness and reduced tendon reflexes.
Sensory impairment follows but is difficult to test in ICU patients.
In other words, the presence of CIPNP can delay the weaning and rehabilitation for weeks or months.
The resulting endoneural edema could induce hypoxia, resulting in severe energy deficits and hereby primary axonal degeneration.
However, there is still no statistical proof for any of these mechanisms in being a true causal factor in the pathogenesis of CIPNP.
Until recently there was no effective treatment to prevent or stop Critical Illness Polyneuropathy.
Also, relative hypoglycaemia during stress is thought to be potentially deleterious for the immune system and for healing (Mizock B A. Am J Med 1995; 98: 75-84).

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Materials and Methods

[0153] In a randomized, double-blind, placebo-controlled, crossover study the effect of NN2211 on beta cell sensitivity to glucose was tested in 10 subjects with type 2 diabetes following a single dose of NN2211 (7.5 μg / kg) or placebo. Using a graded glucose infusion protocol with plasma glucose levels matched over the range of 5 to 12 mmol / L beta cell sensitivity was assessed. Insulin secretion rates (ISR) were estimated by deconvolution of circulating C-peptide concentrations. Findings were compared to responses of 10 healthy, non-diabetic volunteers to the same glucose infusion protocol.

Results

[0154] Compared to placebo, a single dose of NN2211 increased insulin and C-peptide levels, increased ISR area under the curve (AUC) (1130±150 vs. 668±106 pmol / kg; p<0.001), and increased slope of ISR vs. plasma glucose (1.26±0.36 vs. 0.54±0.18 pmol*L / (min*mmol*kg); p<0.014), to values similar to nondiabetic controls who did not receive the drug (ISR AUC 1206±99; s...

example 2

Material and Methods

[0156] In a prospective, 12 week, randomised, double-blind, dose-response, placebo controlled and open label glimepiride study in subjects with type 2 diabetes, the glucose lowering effect of NN2211 was tested with the primary endpoint being the effect on HbA1c after 12 weeks treatment (a recognised measure of overall glycaemic control).

[0157] Altogether 193 patients were equally randomised to receive one of 5 dose levels of NN2211 (0.045, 0.225, 0.45, 0.60, or 0.75 mg), placebo (s.c. injection), or glimepiride (p.o.) all given once daily. Placebo and NN2211 was double-blind, whereas glimepiride was open-label. The dose of glimepiride was adjusted during the first 4 weeks based on glycaemic control with a treatment target of fasting serum glucose<7 mM, with a dose not exceeding 4 mg / day.

Results

[0158] For the primary endpoint of the study HbA1c decreased in all NNC 90-1170 treatment groups, except the one at the lowest dosage. In comparison to the placebo gr...

example 3

[0161] Serves as an example of a study that could determine the effect of NN2211 in critically ill patients in comparison to intensive insulin treatment.

Methods

Study Population

[0162] All mechanically ventilated, adult (age>18y) patients.

Study Design and Treatment protocols

[0163] At ICU admission, and following informed consent, patients are randomized to either strict control of glycemia below 6.1 mmol / L (110 mg / dL) with continuously infused insulin, the ‘intensive insulin schedule’ (IIS), or using NN2211 given once daily (1-5 mg).

Baseline Assessment and Data Collection

[0164] At baseline, demographic, diagnostic and therapeutic information as well as information necessary to determine severity of illness and utilization of ICU resources are obtained from each patient. These include APACHE-II (Acute Physiology and Chronic Health Evaluation) score with higher values indicating more severe illness and simplified Therapeutic Intervention Scoring System (TISS-28) with higher v...

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Abstract

Use of medicament for life saving treatment of critically ill patients and method of treatment. The medicament comprises a GLP-1 compound which effectively controls the blood glucose level.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of application Ser. No. 10 / 359,324 filed Feb. 6, 2003 and claims priority under 35 U.S.C. 119 of Danish application no. PA 2002 00184 filed Feb. 7, 2002 and U.S. provisional application No. 60 / 359,834 filed Feb. 26, 2002, the contents of which are fully incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to methods for prevention, treatment and / or cure of critically ill patients. More specifically, the methods and uses of the invention pertains to administration of a GLP-1 compound or a pharmaceutical medicament comprising a GLP-1 compound to critically ill patients. Furthermore, the present invention relates to a method for marketing GLP-1 compounds and to advertising media used for disseminating information. BACKGROUND OF THE INVENTION [0003] A specific type of polyneuropathy develops in patients that are treated within an intensive care unit (hereinafter also...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/26
CPCA61K38/26A61P17/02A61P25/00A61P29/00A61P3/08A61P43/00A61P7/12A61P3/10
Inventor KNUDSEN, LOTTE BJERRESELMER, JOHANHANSEN, KRISTIAN TAGE
Owner KNUDSEN LOTTE BJERRE