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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Recent updates on GLP-1 agonists: Current advancements & challenges.

Dilip Sharma1, Suril Verma1, Shivani Vaidya1

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Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
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PubMed
Summary

Glucagon-like peptide (GLP)-1 analogs resist DPP-4 degradation, offering improved type-2 diabetes treatment. These GLP-1 drugs show potential for better glucose control without hypoglycemia or weight gain side effects.

Keywords:
DPP-4 inhibitorsGLP-1 agonistsIncretinsType-2 diabetes mellitus

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Area of Science:

  • Pharmacology and Endocrinology
  • Metabolic Diseases
  • Drug Development

Background:

  • Glucagon-like peptide (GLP)-1 is an incretin hormone with diverse therapeutic actions, including neuroprotection and cardio-protection.
  • Its potent glucose-lowering effects in type-2 diabetes mellitus (T2DM) are limited by a short half-life and rapid degradation by dipeptidyl peptidase-4 (DPP-4).

Purpose of the Study:

  • To review Dipeptidyl peptidase-4 (DPP-4) resistant analogs of Glucagon-like peptide (GLP)-1 currently in clinical trials.
  • To discuss the pharmacology, signaling, and pharmacokinetics of these novel GLP-1 analogs.

Main Methods:

  • Literature review of clinical trials and pharmacological studies.
  • Analysis of pharmacokinetic properties (Cmax, Tmax, T1/2, Vd, Bioavailability) of DPP-4 resistant GLP-1 analogs.
  • Comparison of efficacy and side effect profiles with existing T2DM treatments.

Main Results:

  • Several DPP-4 resistant GLP-1 analogs (Exenatide, Liraglutide, Semaglutide, etc.) are in clinical trials.
  • These analogs demonstrate improved pharmacokinetic profiles and sustained therapeutic effects.
  • GLP-1 agonists show promise in managing T2DM with reduced risk of hypoglycemia and weight gain.

Conclusions:

  • DPP-4 resistant GLP-1 analogs represent a significant advancement in T2DM therapy.
  • These agents offer a potentially safer and more effective treatment option compared to current medications.
  • Further clinical evaluation is ongoing to establish the full therapeutic potential of these novel drugs.