📊 Comparative Weight Loss Outcomes of Peptide Therapies
This analysis compares the longitudinal weight loss efficacy of advanced peptide-based therapies across key clinical trials. The therapies include GLP-1 receptor agonists, amylin analogues, and multi-receptor agonists targeting GIPR and GCGR.
Retatrutide, a triple agonist (GLP-1R/GIPR/GCGR), demonstrated the highest efficacy, achieving 24.2% weight loss at 48 weeks. CagriSema, a dual therapy combining semaglutide with the amylin analogue cagrilintide, closely followed with 22.7% at 68 weeks. Tirzepatide reached 20.2% at 72 weeks, with a plateau observed after 48 weeks.
Semaglutide monotherapy achieved 20.7% at 72 weeks, while Mazdutide and Survodutide, both GLP-1R/GCGR co-agonists, ended at 18.6% and 17.0% respectively by 48 weeks. Cagrilintide monotherapy, as expected, resulted in more modest weight reduction (~8.0% at 48 weeks).
Trials were truncated to their respective endpoints, with annotations highlighting early termination or efficacy plateaus to ensure accurate visual interpretation.
| Peptide | Receptor Targets | Mechanism of Action | Weight Loss (%) | Duration | Trial Name | Notes |
|---|---|---|---|---|---|---|
| Semaglutide | GLP-1R | Increases insulin secretion, delays gastric emptying, suppresses appetite. | 20.7% | 72 weeks | STEP UP | Higher-dose formulation; increased efficacy compared to original STEP-1 (~15%). |
| Tirzepatide | GLP-1R + GIPR | Dual incretin agonist; enhances insulin sensitivity and energy expenditure. | 20.2% | 72 weeks | SURMOUNT-5 | Compared against semaglutide; maintained superiority in weight reduction. |
| Cagrilintide | AmylinR | Amylin analogue; CNS-mediated appetite suppression and gastric delay. | ~8% | 26–52 weeks | Multiple Phase 2 Trials | Used alone or in combo with semaglutide in early trials. |
| CagriSema | GLP-1R + AmylinR | Combines incretin and amylin pathways to enhance satiety and glycemic control. | 22.7% | 68 weeks | REDEFINE-1 | Phase 3 trial showing comparable results to tirzepatide. |
| Survodutide | GLP-1R + GCGR | Increases satiety and energy expenditure; reduces hepatic fat. | 19.0% | 46 weeks | Phase 2 MASH Study | Dual indication for obesity and metabolic dysfunction-associated steatohepatitis. |
| Retatrutide | GLP-1R + GIPR + GCGR | Triple agonist; combines incretin and glucagon activity for maximal effect. | 24.2% | 48 weeks | Phase 2 Obesity Study | Highest efficacy observed among all peptide-based weight loss therapies. |
| Mazdutide | GLP-1R + GCGR | Dual action to suppress appetite and increase thermogenesis. | 18.6% | 48 weeks | GLORY-1 (Phase 2) | Developed by Innovent Biologics; nearing global Phase 3. |
