Incretin hormone agonists including liraglutide, semaglutide, and tirzepatide have transformed obesity treatment, with next-generation triple agonists and oral formulations poised to expand options further.
800+ million people affected by obesityObesity is a global health challenge affecting over 800 million individuals, and incretin hormone agonists represent the most significant pharmacological advancement in managing it, with multiple next-generation agents in development.
What the researchers found
Current incretin hormone agonists — liraglutide (SCALE trials), semaglutide (STEP trials), and tirzepatide (SURMOUNT-1) — have demonstrated remarkable efficacy in promoting weight loss and improving metabolic outcomes for obesity. The next generation of obesity drugs in development includes oral GLP-1 receptor agonists, triple agonists targeting GLP-1/GIP/glucagon receptors simultaneously, GLP-1/glucagon receptor co-agonists, oral GIP/GLP-1 co-agonists, and combinations of long-acting amylin receptor agonists with GLP-1 receptor agonists.
Why it matters
With over 800 million people affected by obesity worldwide and traditional lifestyle interventions often producing insufficient or unsustainable weight loss, incretin-based therapies represent the most significant pharmacological advance in obesity management in decades. This review maps the current and emerging landscape, helping clinicians and patients understand what's available now and what's coming next.
How the study worked
Narrative review synthesizing data from key clinical trial programs — SCALE (liraglutide), STEP (semaglutide), and SURMOUNT (tirzepatide) — along with the emerging pipeline of dual and triple incretin agonists. Therapies are categorized by mechanism of action and route of administration.
Who was studied
Review covering adults with obesity eligible for pharmacotherapy, including those with obesity-related comorbidities
What this study cannot tell us
As a narrative review, the article does not use systematic search methodology. Specific weight loss percentages and adverse event data from the named clinical trials are not detailed in the abstract. The emerging therapies discussed are at various stages of development and may not all reach market approval. Long-term (multi-year) safety and weight maintenance data for newer agents remain limited.
How to read the evidence
This is a narrative review synthesizing data from landmark randomized controlled trials (SCALE, STEP, SURMOUNT). While the underlying trial evidence is strong, the review format and narrative approach place it below systematic reviews in the evidence hierarchy. Discussion of emerging therapies is based on preliminary trial data.
When this study was published
Published in 2024, this review captures the current state of the rapidly evolving incretin-based obesity treatment landscape, including both approved agents and the most advanced pipeline candidates.
The bigger picture
The incretin-based obesity drug revolution is still in its early chapters. While semaglutide and tirzepatide have already reshaped clinical practice, the emerging pipeline of oral formulations, triple agonists, and amylin combinations suggests that weight loss efficacy may continue to improve. The shift from injectable-only to oral options could dramatically expand patient access, while multi-receptor targeting may push achievable weight loss closer to surgical outcomes without the associated risks.
Questions still open
- Will triple GLP-1/GIP/glucagon agonists achieve weight loss comparable to bariatric surgery, and at what safety cost?
- Can oral incretin agonists achieve the same efficacy as injectable formulations, or will convenience come with reduced effectiveness?
- How will insurance coverage and pricing evolve as more incretin-based obesity drugs reach the market?
Common questions
What are incretin hormones and why do drugs targeting them cause weight loss?
What's different about the next-generation obesity drugs in development?
Read the original research
Incretin hormone agonists: Current and emerging pharmacotherapy for obesity management.
Pharmacotherapy, 44(9), 738-752
Citation
Alhomoud, Ibrahim S; Talasaz, Azita H; Chandrasekaran, Preethi; Brown, Roy; Mehta, Anurag; Dixon, Dave L. (2024). Incretin hormone agonists: Current and emerging pharmacotherapy for obesity management.. Pharmacotherapy, 44(9), 738-752. https://doi.org/10.1002/phar.4607