A systematic review of 53 phase 2/3 trials identified 36 emerging obesity drugs, with incretin peptide analogs dominating the pipeline and achieving 7.4-24.2% weight loss in completed phase 2 trials.
Up to 24.2% weight lossMaximum mean percent weight loss achieved by incretin-based therapies in completed phase 2 trials — representing the upper range of emerging peptide drug efficacy
What the researchers found
The review identified 53 phase 2/3 trials covering 36 emerging antiobesity drugs or combinations. Key findings:
- Almost half of drugs in phase 2 trials are incretin analogs
- Completed phase 2 incretin-based therapies achieved 7.4-24.2% mean weight loss
- Oral semaglutide 50mg is the only drug to have completed a phase 3 trial
- 14 ongoing phase 3 trials include: GLP-1 RAs (ecnoglutide, orforglipron, TG103), GLP-1/amylin (CagriSema), GLP-1/glucagon dual agonists (mazdutide, survodutide), GLP-1/GIP/glucagon triple agonist (retatrutide)
- 4 trials were withdrawn or terminated
The review highlights that data on mortality, cardiovascular outcomes, long-term safety, cost-effectiveness, and underrepresented populations remain critical gaps.
Why it matters
This review provides the most comprehensive map of the obesity drug pipeline, confirming that peptide-based incretin therapies are the dominant and most promising class. Understanding which peptide drugs are in development, their mechanisms, and their weight loss potential is essential for clinicians, patients, and investors tracking the future of obesity treatment.
How the study worked
Systematic review of phase 2 and phase 3 trials in adults with overweight/obesity, searching Medline, Embase, and ClinicalTrials.gov from 2012 to 2024. Trials comparing novel weight loss pharmacotherapies to placebo/control or FDA-approved weight loss medication were included.
What this study cannot tell us
The review covers trials through 2024 and may miss newer developments. Only phase 2 and 3 trials were included, so earlier-stage peptide drugs are not covered. Many included trials are ongoing with incomplete results. The review cannot compare drugs directly across different trials due to varying study designs, populations, and endpoints. Long-term data (>2 years) is limited for most emerging agents.
How to read the evidence
This is a systematic review of clinical trials — a high level of evidence synthesis. The review methodology (multiple databases, 2012-2024 coverage) is rigorous. However, many included trials are phase 2 with small samples and short durations, and several are still ongoing without final results.
When this study was published
Published in 2025 in Pharmacological Reviews (a high-impact journal), this is the most current and comprehensive systematic review of the obesity drug pipeline available.
The bigger picture
The obesity drug landscape is being fundamentally reshaped by peptide science. From single GLP-1 agonists to dual (GLP-1/GIP, GLP-1/glucagon) and triple (GLP-1/GIP/glucagon) agonists, the progression represents iterative peptide engineering aimed at mimicking and amplifying the body's natural satiety and metabolic signals. This review captures a historic moment where dozens of peptide-based therapies are simultaneously advancing through clinical trials.
Questions still open
- Will triple agonists like retatrutide achieve greater weight loss than dual agonists like tirzepatide?
- How will oral peptide formulations (oral semaglutide 50mg, orforglipron) change patient acceptance and adherence compared to injectables?
- Which of these 36 emerging drugs will ultimately reach the market, and will they be cost-effective for widespread use?
Common questions
What new weight loss drugs are coming after semaglutide?
Will there be weight loss pills as effective as injections?
Read the original research
Emerging pharmacotherapies for obesity: A systematic review.
Pharmacological reviews, 77(1), 100002
Citation
Kokkorakis, Michail; Chakhtoura, Marlene; Rhayem, Caline; Al Rifai, Jana; Ghezzawi, Malak; Valenzuela-Vallejo, Laura; Mantzoros, Christos S. (2025). Emerging pharmacotherapies for obesity: A systematic review.. Pharmacological reviews, 77(1), 100002. https://doi.org/10.1124/pharmrev.123.001045