GLP-1 Analog Peptides

An investigational single-molecule GLP-1 and amylin receptor agonist from Novo Nordisk, now named zenagamtide, studied as a once-weekly injection and a once-daily tablet for obesity and type 2 diabetes. It is not approved anywhere.

An investigational long-acting amylin analogue from Novo Nordisk, studied alone and with semaglutide (CagriSema). In the phase 3 REDEFINE 1 trial, CagriSema produced a mean 20.4% weight loss at 68 weeks (vs 3.0% on placebo). Not FDA-approved.

CagriSema is Novo Nordisk's investigational once-weekly combination of the amylin analogue cagrilintide 2.4 mg and semaglutide 2.4 mg. It produced 20.4% mean weight loss at 68 weeks in REDEFINE 1; it is not FDA-approved.

Dulaglutide (Trulicity) is an FDA-approved once-weekly GLP-1 receptor agonist fusion protein prescribed for type 2 diabetes mellitus and cardiovascular risk reduction. It consists of a modified GLP-1 analog covalently linked to a human IgG4 Fc fragment, enabling convenient once-weekly subcutaneous dosing.

A once-weekly, cAMP-biased GLP-1 receptor agonist engineered to preferentially signal through the cAMP pathway. Investigated for type 2 diabetes and obesity, with both subcutaneous and oral formulations under development.

A once-weekly, exendin-based GLP-1 receptor agonist built on an antibody Fc fusion scaffold. Notable for the AMPLITUDE-O cardiovascular outcomes trial, which showed reductions in major cardiovascular and renal events in high-risk type 2 diabetes.

Exenatide is the first FDA-approved GLP-1 receptor agonist, a synthetic 39-amino-acid peptide derived from exendin-4 found in the saliva of the Gila monster (Heloderma suspectum). Available as Byetta (twice-daily injection) and Bydureon (once-weekly extended-release microsphere injection), it lowers blood glucose in type 2 diabetes by enhancing glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting satiety.

A 42-amino-acid incretin hormone secreted by K-cells in the duodenum and jejunum that potentiates glucose-dependent insulin secretion and plays a central role in the mechanism of tirzepatide and retatrutide.

The first GLP-1 receptor agonist approved for chronic weight management (Saxenda, 2014) — an acylated human GLP-1 analog with ~13-hour half-life dosed once daily.

Lixisenatide is an FDA-approved 44-amino-acid GLP-1 receptor agonist derived from exendin-4, prescribed for the treatment of type 2 diabetes mellitus. Marketed as Adlyxin in the US and Lyxumia in Europe, it is also available in a fixed-ratio combination with insulin glargine (Soliqua 100/33) for comprehensive glycemic control.

A once-weekly injectable dual agonist of the GLP-1 and glucagon receptors. China's NMPA approved mazdutide in 2025 for chronic weight management and for type 2 diabetes; it is not FDA-approved and remains investigational in the US.

An 82-amino-acid anorexigenic peptide derived from nucleobindin-2 (NUCB2) that suppresses appetite through hypothalamic signaling and crosses the blood-brain barrier, studied for potential anti-obesity applications.

Orforglipron (Foundayo) is a once-daily oral, non-peptide GLP-1 receptor agonist from Eli Lilly. The FDA approved it on April 1, 2026 for chronic weight management, and the UK MHRA authorised it in August 2026 for weight management and type 2 diabetes.

A 37-amino-acid proglucagon-derived gut hormone from intestinal L-cells that activates both the GLP-1 and glucagon receptors — reducing appetite while increasing energy expenditure. The natural template for today's dual and triple co-agonist drugs.

Oral semaglutide co-formulated with SNAC (sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) absorption enhancer — the first peptide-based GLP-1 receptor agonist available as a daily oral tablet (Rybelsus), FDA-approved for type 2 diabetes.

A dual GLP-1/glucagon receptor agonist developed by Altimmune for MASH and obesity, designed to leverage glucagon-driven hepatic fat reduction alongside GLP-1-mediated appetite suppression.

An investigational long-acting human amylin analog from Zealand Pharma, given as a once-weekly injection for obesity. In the 42-week ZUPREME 1 phase 2 trial it produced about 8–10% mean weight loss at 28 weeks, with nausea as the main side effect. Not approved anywhere.

Pramlintide (Symlin) is an FDA-approved synthetic analog of amylin, the 37-amino-acid hormone co-secreted with insulin by pancreatic beta cells. Injected subcutaneously before major meals, it is approved only as an add-on to mealtime insulin in type 1 and type 2 diabetes, where it slows gastric emptying, reduces the post-meal rise in glucagon, and reduces food intake. Drugs@FDA now lists the Symlin products as discontinued.

Long-acting GLP-1 receptor agonist — FDA-approved for type-2 diabetes and chronic weight management, landmark for its ~15% mean weight reduction in STEP trials.

A dual GLP-1/glucagon receptor agonist in phase 3 development by Boehringer Ingelheim for MASH (metabolic dysfunction-associated steatohepatitis) and obesity, with strong liver-directed efficacy signals.

A triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) originally developed for neurodegenerative diseases, repurposed for obesity after demonstrating significant weight loss in clinical trials.