Weight Loss Peptides

Semaglutide holds four FDA approvals for obesity, type 2 diabetes, and cardiovascular risk reduction. STEP 1 confirmed 14.9% mean weight loss at 68 weeks. The 7.2 mg high-dose version (March 2026) pushes that to 20.7%. GI side effects are real but manageable with slow titration.

Tirzepatide targets both GIP and GLP-1 receptors, producing 20-22% body weight loss in important trials. FDA-approved as Zepbound (obesity) and Mounjaro (T2D). GI side effects during titration are the main limiting factor; a black box warning for thyroid tumors applies.

Retatrutide is a triple-agonist peptide (GLP-1, GIP, glucagon) that produced 28.7% weight loss in Phase 3 at 68 weeks. Not yet FDA approved. Strongest clinical weight loss data of any drug tested to date, with liver fat reduction exceeding 80% in MASLD subgroups.

Liraglutide is an FDA-approved GLP-1 receptor agonist with 15+ years of market data and proven cardiovascular protection from the LEADER trial (n=9,340). Less potent than semaglutide for weight loss, but side effects clear in a day thanks to its 13-hour half-life.

Dulaglutide (Trulicity) is a once-weekly GLP-1 receptor agonist with FDA approval for type 2 diabetes and cardiovascular risk reduction. The REWIND trial confirmed a 12% drop in major cardiovascular events over 5.4 years in 9,901 participants. Pre-filled pen, no mixing, no needle. Weight loss is modest compared to newer options.

5-Amino-1MQ blocks the fat-cell enzyme NNMT, boosting NAD+ and cellular energy burn. Mouse studies show dose-dependent fat loss and metabolic improvement; a 2024 study added grip strength gains in aged animals. No human trials exist. Oral capsules are the community standard, though rodent data questions that route. Research compound only.

AOD-9604 targets fat cells through the beta-3 adrenergic receptor, a mechanism separate from appetite-based weight loss drugs. Phase IIa data showed 2.8 kg fat loss at 12 weeks. The Phase IIb trial failed its primary endpoint. Community users treat it as a mild recomposition stacking add-on, not a standalone solution.

CagriSema combines cagrilintide and semaglutide for 22.7% weight loss in the REDEFINE 1 trial of 3,417 adults, outperforming semaglutide alone by seven points. NDA filed December 2025. GI events hit 80% of participants, the highest rate in the GLP-1 class.

Orforglipron (Foundayo) is the first oral non-peptide GLP-1 receptor agonist, FDA-approved April 2026. No injections, no fasting restrictions. The ATTAIN-1 trial showed 12.4% average weight loss at 72 weeks, though GI side effects run higher than comparable injectable GLP-1 drugs.

Lipo-C is a compounded lipotropic injection mixing MIC (Methionine, Inositol, Choline) with L-Carnitine and B vitamins. Clinics prescribe it alongside GLP-1 agonists for metabolic support during caloric restriction. L-carnitine meta-analyses confirm modest fat loss effects; the combined formula itself has zero RCTs. Pre-mixed, no reconstitution required.

Setmelanotide (IMCIVREE) is the only FDA-approved MC4R agonist for rare genetic obesity. Phase 3 data showed 25.6% mean weight loss in POMC-deficient patients at 52 weeks. Strict genetic testing required; does not work for common polygenic obesity. Prescription only, administered as a daily injection.

Mazdutide is a dual GLP-1 and glucagon agonist that hit 20% weight loss at 60 weeks in Phase 3 trials. NMPA-approved in China but not yet available through Western pharmacies. The glucagon component adds thermogenic fat burning that GLP-1-only drugs can't match.

Pemvidutide (ALT-801) combines GLP-1 and glucagon receptor activation in a single weekly injection. Phase 2 data: 15.6% weight loss plus up to 76% liver fat reduction. FDA Breakthrough Therapy Designation for MASH granted January 2026. Currently, clinical trial access only.

Exenatide was the first FDA-approved GLP-1 receptor agonist for type 2 diabetes. Both Byetta (twice daily) and Bydureon (weekly) were discontinued in October 2024. Complete clinical data, side effect profile, and transition guidance covered here. Generic options may follow.

Pramlintide (Symlin) is the only FDA-approved amylin analog, replacing a hormone absent in T1D and impaired in T2D. Flattens postprandial glucose 3.4 to 5 mmol/L beyond insulin alone. Carries a black box warning for hypoglycemia. Commercially discontinued in October 2025.

Lixisenatide is a short-acting GLP-1 receptor agonist with four-fold higher receptor binding than native GLP-1. FDA-approved for type 2 diabetes, confirmed cardiovascular-neutral in 6,068 patients. Standalone US product discontinued; available as Soliqua 100/33 with insulin glargine in a fixed-dose combination.

Tesofensine is a triple monoamine reuptake inhibitor that produced 9.2% body weight loss in 24 weeks at 0.5 mg daily. Oral capsule, no injection. Not FDA-approved; Phase 3 complete in Mexico. Heart rate monitoring required during the full treatment course.

Cagrilintide activates amylin receptors, a pathway GLP-1 drugs miss entirely. REDEFINE 1 confirmed 11.5% weight loss as monotherapy and 20.4% combined with semaglutide at 68 weeks. CagriSema NDA is under FDA review. All standalone supply remains research-grade with no regulatory oversight.

Danuglipron was Pfizer's oral small-molecule GLP-1 agonist. Phase 2b trials showed 5 to 13 percent weight loss at 32 weeks, but severe GI side effects caused over 50 percent dropout. Development stopped in April 2025 after a drug-induced liver injury signal.

Survodutide is a dual GLP-1/glucagon agonist with Phase 2 data showing 80% liver fat reduction and 18.7% weight loss. Currently in Phase 3 trials for MASH and obesity. Not yet FDA-approved; Boehringer Ingelheim Phase 3 results pending in 2026 or 2027.

Adipotide (FTPP) destroyed 38% of total body fat in primate studies by cutting off blood supply to fat tissue. Clinical development was permanently halted after kidney toxicity appeared at sub-therapeutic doses. No safe human dose has been identified, and all clinical development ended permanently in 2019.