Best Peptides for Weight Loss

Retatrutide (LY3437943) is a first-in-class triple agonist peptide targeting GIP, GLP-1, and glucagon receptors simultaneously. Developed by Eli Lilly, it is currently in Phase 3 clinical trials and has demonstrated the highest weight loss of any obesity medication to date — up to 28.7% body weight reduction at 48 weeks. The triple-receptor mechanism represents the next evolution beyond dual agonists like tirzepatide.

Phase 2: 28.7% body weight loss at 48 weeks (12 mg), highest of any obesity medication to date. Phase 3 results expected 2026-2027.

Tirzepatide is the first dual GIP/GLP-1 receptor agonist — a 39-amino acid synthetic peptide that activates both the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. FDA-approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound). In clinical trials, tirzepatide demonstrated greater weight loss than semaglutide, with up to 22.5% body weight reduction at the highest dose.

SURMOUNT-1: 20.9% body weight reduction at 72 weeks (15 mg dose). Superior to semaglutide 2.4 mg in SURMOUNT-5 head-to-head trial.

Liraglutide is a GLP-1 receptor agonist — a 31-amino acid peptide analog with 97% homology to native human GLP-1. FDA-approved for type 2 diabetes (Victoza, 2010) and chronic weight management (Saxenda, 2014). It was the first GLP-1 agonist approved specifically for obesity. Liraglutide has a shorter half-life than semaglutide (13 hours vs 7 days), requiring daily rather than weekly dosing.

SCALE Obesity: 8.0% body weight reduction at 56 weeks (3.0 mg daily). Less than semaglutide/tirzepatide but longest safety record.

Semaglutide is a GLP-1 receptor agonist — a 31-amino acid peptide analog of human glucagon-like peptide-1 (GLP-1) with a 94% sequence homology to native GLP-1. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy). Semaglutide has an albumin-binding fatty acid side chain that extends its half-life to approximately 7 days, enabling once-weekly dosing. It is the most widely prescribed GLP-1 medication globally, with over 25 million Americans expected to be on GLP-1 therapy by 2030.

Average 14.9% body weight reduction at 68 weeks in STEP 1 trial (2.4 mg weekly). Oral Wegovy (25 mg daily) showed 15.8% reduction.

Orforglipron (LY3502970) is a non-peptide, oral GLP-1 receptor agonist developed by Eli Lilly. Unlike oral semaglutide (which is a peptide requiring special formulation), orforglipron is a small molecule — the first of a new class of oral GLP-1 drugs that can be taken without fasting restrictions. It is in Phase 3 trials for obesity and type 2 diabetes, with an FDA decision expected in 2026. Projected to reach $16 billion in annual sales by 2031.

Phase 2: 14.7% weight loss at 36 weeks (45 mg daily). Phase 3 ATTAIN-1 trial results expected 2026.

CagriSema is a fixed-ratio combination of cagrilintide (a long-acting amylin analog) and semaglutide, developed by Novo Nordisk. By combining two distinct appetite-regulating peptide hormones, CagriSema aims to achieve greater weight loss than semaglutide alone. Phase 3 data showed 22.7% body weight reduction, and an FDA response is expected in 2026.

REDEFINE-1: 22.7% body weight loss at 68 weeks, superior to semaglutide 2.4 mg alone (15.8%). Combines two distinct appetite pathways.

Survodutide (BI 456906) is a dual GLP-1/glucagon receptor agonist developed by Boehringer Ingelheim in partnership with Zealand Pharma. It is being developed primarily for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and obesity. Survodutide's glucagon receptor activation promotes hepatic fat mobilization, making it uniquely suited for liver-related metabolic conditions.

Phase 2b: 18.7% weight loss at 46 weeks (6 mg dose). Phase 3 ACHIEVE program is underway.