Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data

@article{Gallwitz2006ExenatideIT,
  title={Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data},
  author={Baptist Gallwitz},
  journal={International Journal of Clinical Practice},
  year={2006},
  volume={60}
}
  • B. Gallwitz
  • Published 1 December 2006
  • Medicine, Biology
  • International Journal of Clinical Practice
The therapeutic options for treating type 2 diabetes have been widened by the introduction of exenatide as the first incretin mimetic. Incretins are gut hormones that contribute to the stimulation of insulin secretion after a carbohydrate rich meal. The incretin hormone glucagon‐like peptide‐1 (GLP‐1) not only stimulates insulin secretion under hyperglycaemic conditions, but also suppresses glucagon secretion, slows gastric emptying, induces satiety and improves beta cell function in type 2… 
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  • Medicine, Biology
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  • 2008
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TLDR
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TLDR
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TLDR
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GLP-1 agonists and dipeptidyl-peptidase IV inhibitors.
  • B. Gallwitz
  • Biology, Medicine
    Handbook of experimental pharmacology
  • 2011
TLDR
An overview on the mechanism of action and the substances and clinical data available is given and GLP-1 receptor agonists allow weight loss; DPP-4 inhibitors are weight neutral.
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References

SHOWING 1-10 OF 34 REFERENCES
Therapies for the treatment of type 2 diabetes mellitus based on incretin action.
  • B. Gallwitz
  • Medicine, Biology
    Minerva endocrinologica
  • 2006
TLDR
In vitro and animal data demonstrated that GLP-1 increases beta cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets, and may represent an attractive therapeutic method for type 2 diabetes due to its multiple effects also including the simulation of satiety in the central nervous system by acting as transmitter or by crossing the blood brain barrier.
Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes.
TLDR
In conclusion, AC2993 acutely and markedly reduces fasting and postprandial glucose concentrations in patients with type 2 diabetes.
Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes.
TLDR
AC2993 had significant effects on HbA(1c) levels in patients not currently achieving optimal glucose control with diet and/or OAAs, confirming AC2993 effects on fasting and postprandial glycemia.
Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005
TLDR
The incretin mimetics, administered by sc injection, have demonstrated lasting improvement in HbA1c in patients insufficiently treated with conventional oral therapy, and their use has been associated with steady weight loss for up to 2 years.
Entero-insular axis and diabetes mellitus.
  • W. Creutzfeldt
  • Medicine, Biology
    Hormone and metabolic research. Supplement series
  • 1992
TLDR
The incretin effect is reduced in type 2 diabetes although GIP secretion is normal or exaggerated, which suggests an insensitivity of the diabetic B-cell to GIP, and could also indicate the lack of another not yet defined "incretin".
Day-long subcutaneous infusion of exenatide lowers glycemia in patients with type 2 diabetes.
TLDR
Exenatide lowered plasma glucose during both prandial and fasting states when delivered as a continuous SC infusion over twenty-three hours, suggesting that exen atide can provide day-long glycemic control in patients with type 2 diabetes.
Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes.
TLDR
Short-term exposure to exenatide can restore the insulin secretory pattern in response to acute rises in glucose concentrations in DM2 patients who, in the absence of exen atide, do not display a first phase of insulin secretion.
Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea.
TLDR
Exenatide significantly reduced A1C in patients with type 2 diabetes unable to achieve adequate glycemic control with maximally effective doses of combined metformin-sulfonylurea therapy, associated with no weight gain and was generally well tolerated.
Exendin‐4, a glucagon‐like protein‐1 (GLP‐1) receptor agonist, reverses hepatic steatosis in ob/ob mice
TLDR
Exendin‐4 appears to effectively reverse hepatic steatosis in ob/ob mice by improving insulin sensitivity and the data suggest that GLP‐1 proteins in liver have a novel direct effect on hepatocyte fat metabolism.
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