GLP-1 / Weight Loss Agonists

GLP-1, GIP, and glucagon receptor agonists used for metabolic health and weight management.

Cagrilintide

Cagrilintide is a long-acting amylin analog developed by Novo Nordisk. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells. Cagrilintide slows gastric emptying, suppresses glucagon, and reduces appetite via central amylin receptors. In combination with semaglutide (CagriSema), Phase 2 trials achieved approximately 15% body weight reduction. Phase 3 trials (REDEFINE program) are ongoing.

Dulaglutide

Dulaglutide (brand name Trulicity) is a once-weekly GLP-1 receptor agonist approved by the FDA for type 2 diabetes management and cardiovascular risk reduction. It consists of two GLP-1 analog chains fused to a modified IgG4 Fc fragment, extending its half-life to approximately 5 days. While primarily a diabetes medication, it produces meaningful weight loss and has established cardiovascular outcomes data from the REWIND trial.

Eloralintide

Eloralintide is a long-acting amylin analog under development by OPKO Health. Amylin is co-secreted with insulin and regulates post-meal glucose by slowing gastric emptying, suppressing glucagon, and promoting satiety. Eloralintide is designed for once-weekly dosing, differentiating it from the short-acting pramlintide (Symlin). It is being studied for obesity and type 2 diabetes as a complement to GLP-1 based therapies.

Enclomiphene

Enclomiphene is the trans-isomer of clomiphene citrate, a selective estrogen receptor modulator (SERM) that stimulates endogenous testosterone production by blocking estrogen negative feedback on the hypothalamus and pituitary. Unlike TRT, it restores testosterone while preserving or increasing sperm production and testicular volume.

Exenatide

Exenatide is a GLP-1 receptor agonist derived from the Gila monster lizard peptide exendin-4, with 53% homology to human GLP-1 and natural resistance to DPP-4 degradation. Available as twice-daily (Byetta) or once-weekly (Bydureon) formulation, it is also being studied for Parkinson's disease neuroprotection.

Liraglutide

Liraglutide is a long-acting GLP-1 receptor agonist approved for type 2 diabetes (Victoza) and chronic weight management (Saxenda). It reduces appetite, slows gastric emptying, improves insulin secretion, and promotes weight loss of 5–10% in clinical trials.

Mazdutide

Mazdutide is a once-weekly GLP-1/glucagon dual receptor agonist developed by Innovent Biologics and Eli Lilly. Phase 2 trials in Chinese populations demonstrated up to 11.3% body weight reduction at 6 mg over 24 weeks. It also improves liver fat, glycemic control, and lipid profiles. Phase 3 trials are ongoing primarily in China.

Orforglipron

Orforglipron is an oral, once-daily small-molecule GLP-1 receptor agonist developed by Eli Lilly. Unlike injectable GLP-1 peptides, it is a non-peptide compound absorbed orally without food restrictions, representing a major convenience advancement. Phase 2 trials showed up to 9.4% weight loss at 36 weeks, and Phase 3 trials (ATTAIN program) are ongoing for obesity and type 2 diabetes.

Retatrutide

Retatrutide is an investigational triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. Phase 2 trials showed an unprecedented average 24% body weight reduction at 48 weeks — exceeding any approved medication to date. It is in Phase 3 trials as of 2024.

Semaglutide

Semaglutide is an FDA-approved GLP-1 receptor agonist originally developed for type 2 diabetes that has proven remarkably effective for weight loss. Clinical trials show average 15–20% body weight reduction. It is marketed as Ozempic (diabetes) and Wegovy (weight management).

Semaglutide

Semaglutide is a highly potent, once-weekly GLP-1 receptor agonist approved for type 2 diabetes (Ozempic) and chronic weight management (Wegovy). With 94% homology to human GLP-1 and albumin-binding modification, it delivers 15–20% average weight loss — the most effective GLP-1 agent available.

Survodutide

Survodutide is a once-weekly GLP-1/glucagon dual receptor agonist developed by Boehringer Ingelheim and Zealand Pharma. Phase 2 trials demonstrated up to 18.7% body weight reduction at 46 weeks, among the highest reported for a dual agonist. It is being studied for obesity and MASH (metabolic dysfunction-associated steatohepatitis), where the glucagon component drives hepatic fat clearance.

Tirzepatide

Tirzepatide is an FDA-approved dual GIP/GLP-1 receptor agonist that produces greater weight loss than semaglutide in head-to-head trials. SURMOUNT-1 trial showed average 21% body weight reduction at 72 weeks at the highest dose. Marketed as Mounjaro (diabetes) and Zepbound (obesity).