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Novel Dual and Triple Agonists Targeting GLP-1, GIP, Glucagon, and GDF15 for Type 2 Diabetes and Obesity Management

Jiudan Zhang1,2, Shriya Sanan3, Marta Csanalosi2

  • 1Department of Endocrinology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Endocrinology
|August 16, 2025
PubMed

Insights

Novel dual and triple agonists targeting GLP-1, GIP, glucagon, and GDF15 show promise for managing type 2 diabetes mellitus (T2DM) and obesity, offering enhanced glycemic control and weight loss with potential organ benefits.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Diabetology

Background:

  • Obesity is a major driver of insulin resistance and type 2 diabetes mellitus (T2DM).
  • Existing treatments like SGLT2 inhibitors and GLP-1 receptor agonists are effective but not universally sufficient.
  • There is a need for novel therapeutic strategies to address the growing global burden of T2DM and obesity.

Purpose of the Study:

  • To review emerging dual and triple agonist therapies targeting multiple metabolic pathways.
  • To highlight the clinical importance and preclinical progress of novel peptide-based agents.
  • To provide an overview of the evolving landscape of antidiabetic pharmacotherapy.

Main Methods:

  • Literature review focusing on novel dual and triple agonists.
  • Analysis of agents targeting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and growth differentiation factor 15 (GDF15).
  • Exclusion of amylin analogs for future review.

Main Results:

  • Novel agents, particularly GLP-1/GIP, GLP-1/GDF15, and GLP-1/GIP/glucagon combinations, demonstrate enhanced glycemic control and weight loss.
  • These agents offer potential renal, neurological, cardioprotective, and anti-inflammatory benefits.
  • Emerging evidence supports multifaceted metabolic improvements.

Conclusions:

  • Novel dual and triple agonists represent a promising advancement in T2DM pharmacotherapy.
  • These agents leverage multiple pathways for improved metabolic outcomes.
  • Careful evaluation of safety profiles and potential adverse effects is crucial for clinical application.
Keywords:
GLP-1/GIP/GDF15/glucagondual/triple agonistsobesitytype 2 diabetes

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