The drug classes, what each one targets, and where the evidence actually stands. Research framing — no medical advice.
After you eat, your gut releases hormones — incretins — that tell your brain you're full, slow how fast food leaves your stomach, and help regulate blood sugar. The modern weight-loss compounds are engineered versions of these hormones, modified to last days instead of minutes in the body.
The foundation of the class. Semaglutide is the most studied example: in the 68-week STEP-1 trial, participants lost a mean 14.9% of body weight. These compounds are approved medicines with safety data across tens of thousands of patients.
Tirzepatide (GIP + GLP-1) showed a mean 20.9% weight loss at 72 weeks in SURMOUNT-1 — the strongest result of any approved medicine. Mazdutide and survodutide take the other dual path, pairing GLP-1 with glucagon agonism to add energy expenditure to appetite suppression. Mazdutide is approved in China after phase 3 trials reporting up to 18.55% mean loss.
Retatrutide engages GIP, GLP-1, and glucagon receptors simultaneously. Its phase 2 readout — 24.2% mean weight loss at 48 weeks, published in the New England Journal of Medicine — was the largest ever reported in an obesity trial at the time. Phase 3 is underway.
A separate satiety pathway. Amylin is co-secreted with insulin and acts on brainstem receptors to deepen fullness. Cagrilintide (phase 3) and eloralintide (phase 2) are the long-acting analogues bringing this pathway into once-weekly research — and both now anchor combination products: CagriSema (cagrilintide + semaglutide, phase 3) and EloraTZP (eloralintide + tirzepatide, phase 1), each stacking the amylin pathway with an incretin in a single injection.
Three tiers. Tier 1: approved medicines with large phase 3 programs (semaglutide, tirzepatide). Tier 2: investigational compounds with published human trial data (retatrutide, cagrilintide, survodutide, eloralintide, mazdutide, CagriSema, EloraTZP, VK2735). Tier 3: animal and preclinical research only — no human trials. Nothing Tier 3 is listed. If the human evidence isn't there, the compound isn't here.
