Orforglipron

Semaglutide is a GLP-1 receptor agonist, a peptide engineered to mimic the natural gut hormone GLP-1 but with a roughly week-long half-life so it can be dosed once weekly. It is FDA-approved and sold as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for chronic weight management, with cardiovascular benefit also on the label. This is one of the most rigorously tested peptides in existence, backed by large randomized trials, so the evidence here is in a completely different league from research-only peptides.

Tirzepatide is a single peptide that activates two receptors at once: GIP and GLP-1, the two main incretin hormones your gut releases after eating. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for chronic weight management and obstructive sleep apnea, and it has produced the largest weight-loss numbers of any approved drug to date. Like semaglutide, this is a heavily trialed, fully approved medicine, not a gray-market research compound.

Liraglutide is a once-daily injectable GLP-1 receptor agonist, a synthetic peptide that shares about 97% of its sequence with the natural gut hormone GLP-1 but is engineered with a fatty acid chain so it survives in the body far longer. It is FDA-approved as Victoza for type 2 diabetes (2010) and as Saxenda for chronic weight management (2014), and is one of the most studied drugs in its class. As of 2024 a generic version is also FDA-approved.

Dulaglutide (brand name Trulicity) is a once-weekly injectable GLP-1 receptor agonist made by fusing a modified GLP-1 peptide to a fragment of a human antibody, which is what lets it last a full week between shots. It is FDA-approved for type 2 diabetes and, notably, to reduce cardiovascular risk in adults with diabetes. The once-weekly dosing made it a major convenience step up from earlier daily and twice-daily agents.

Exenatide is the original GLP-1 receptor agonist and it came from an unlikely source: the saliva of the Gila monster, a venomous desert lizard. It is a synthetic 39-amino-acid peptide (a copy of the natural exendin-4) sharing about 50% of its sequence with human GLP-1, sold as the twice-daily Byetta (FDA-approved 2005) and the once-weekly Bydureon. It was the first drug to successfully turn the short-lived incretin hormone into a real diabetes therapy.

Oral semaglutide is the pill version of the same GLP-1 peptide found in Ozempic and Wegovy, sold for type 2 diabetes as Rybelsus. The trick that makes it work is an absorption enhancer called SNAC, which shields the peptide from stomach acid and helps it cross the gut lining. Lower doses are approved for diabetes, and higher 25 mg doses have now been approved as the first GLP-1 pill for weight loss.