Metabolics & Appetite

The metabolic shelf collects long-acting incretin-receptor agonists characterised in the largest peptide drug-development programmes of the last decade. Each compound is a fatty-acid-acylated analogue of native gut hormones — engineered to bind albumin via a C18 or C20 diacid side chain, extending circulating half-life from minutes (native GLP-1) to ~5–7 days. The published literature here is unusually deep: STEP, SUSTAIN, SURPASS, SURMOUNT, and SELECT phase 3 trial programmes collectively span tens of thousands of subjects across glycaemic, body-weight, hepatic-fat, renal, and cardiovascular endpoints.

Semaglutide is a 31-amino-acid GLP-1 receptor agonist — the foundation compound, characterised across the STEP obesity trials (0.25 → 2.4 mg weekly), the SUSTAIN type 2 diabetes programme (0.5 / 1.0 mg weekly), and SELECT (cardiovascular outcomes in obesity without diabetes). Tirzepatide is a 39-amino-acid dual GIP/GLP-1 receptor agonist; its SURPASS and SURMOUNT programmes used a 5 / 10 / 15 mg weekly dose ladder. Retatrutide is the investigational triple agonist (GIP / GLP-1 / glucagon) currently in phase 2; published dose-ranging used 1 / 4 / 8 / 12 mg weekly in obesity and MASLD research cohorts.

Researchers comparing them generally do so on receptor coverage (mono vs dual vs triple), trial-published dose ranges, and the body-composition or hepatic-fat endpoint under study. Clinical-trial dose ranges in the published literature are not general-use protocols. For research use only.