Hormonal
Triple receptor agonists (retatrutide) produce the highest magnitude of weight loss reported to date in pharmacotherapy for obesity, surpassing dual and single GLP-1 agonists.
Retatrutide is currently the most effective drug for weight loss in this class, working by targeting three hormonal pathways (GLP-1, GIP, and glucagon). It is administered once weekly. Expect significant weight loss, but also expect gastrointestinal side effects like nausea during the initial weeks, which typically subside.
Triple receptor agonists, such as retatrutide, achieve the most pronounced reductions in body weight reported to date in pharmacotherapy.
Why this rating
Based on Phase 2 RCTs (Sanyal et al., 2024), which are high quality but lack the long-term Phase 3 data mentioned as a future need.
Source
INCRETIN-BASED PHARMACOTHERAPY FOR OBESITY: A COMPARATIVE NARRATIVE REVIEW OF GLP-1, DUAL AND TRIPLE AGONISTS AND COMBINATION THERAPIES
Łukasz Krzystek et al. · International Journal of Innovative Technologies in Social Science · 2025
DOI 10.31435/ijitss.4(48).2025.4388
More from this paper
- Combination therapy of semaglutide and cagrilintide (CagriSema) produces weight loss comparable to multi-receptor agonists by targeting complementary metabolic pathways.Good
- Dual GIP/GLP-1 receptor agonists (tirzepatide) demonstrate enhanced efficacy compared to single GLP-1 agonists, likely due to synergistic modulation of GIP and GLP-1 pathways.Good
- GLP-1 receptor agonists (liraglutide, semaglutide) reduce body weight and improve metabolic parameters by modulating central appetite pathways and delaying gastric emptying.Good
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
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- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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