Next-generation GLP-1 drugs: retatrutide, amycretin, oral agonists, and other pipeline breakthroughs | Research

The takeaway

Next-generation GLP-1 therapies include multi-receptor agonists (retatrutide, survodutide, CagriSema), GIP antagonists (maridebart cafraglutide), and oral small molecules (danuglipron, orforglipron), offering enhanced efficacy and patient-friendly delivery.

Multiple new mechanisms in pipeline
Triple agonists, GIP antagonists, amylin combos, and oral small molecules are reshaping the GLP-1 landscape beyond current approved drugs

What the researchers found

Pipeline agents: retatrutide (triple), survodutide/mazdutide (GLP-1/glucagon), CagriSema/amycretin (amylin+GLP-1), maridebart cafraglutide (GIPR antagonist+GLP-1R agonist), danuglipron/orforglipron (oral small molecules). Multiple mechanisms under development.

Why it matters

Understanding the next wave of metabolic drugs helps clinicians and patients anticipate future options. Multiple agents in late-stage development could offer even greater efficacy than current best-in-class treatments.

How the study worked

Narrative review of clinical development pipeline for novel GLP-1-based agents, excluding approved drugs.

What this study cannot tell us

Review of agents in development—many may not reach approval. Comparative efficacy data limited. Long-term safety unknown for most agents.

How to read the evidence

Review of clinical development data. Evidence ranges from phase 2 to phase 3 across agents.

When this study was published

Published in 2025.

The bigger picture

The metabolic drug landscape is undergoing unprecedented innovation. Within 3-5 years, clinicians may have 10+ incretin-based agents to choose from, each targeting different receptor combinations for personalized obesity and diabetes treatment.

Questions still open

Which combination of receptor targets will prove optimal?
Will oral GLP-1 agonists match injectable efficacy?
How will the market accommodate 10+ competing incretin agents?

Common questions

What comes after semaglutide and tirzepatide?

A wave of next-generation drugs including triple agonists (retatrutide targeting 3 receptors), amylin combinations (CagriSema), oral pills that work like injections (orforglipron, danuglipron), and innovative GIPR antagonist-GLP-1R agonist hybrids. These may offer even greater weight loss and metabolic improvement.

Will we ever have an obesity pill as effective as injections?

Likely yes. Oral non-peptide GLP-1 agonists like orforglipron and danuglipron are in late-stage development and resist digestive breakdown. If approved, they could match injectable efficacy in a convenient daily pill—removing the injection barrier that limits current GLP-1 drug uptake.

Read the original research

Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity.

Endocrine reviews

View on PubMed ↗Publisher’s paper ↗

Citation

Son, Jang Won; le Roux, Carel W; Blüher, Matthias; Nauck, Michael A; Lim, Soo. (2025). Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity.. Endocrine reviews. https://doi.org/10.1210/endrev/bnaf036