Weight-loss peptides compared by the strength of human trial data

If "best" means the most evidence that a compound lowers body weight in people, the answer today is tirzepatide and semaglutide, followed by retatrutide and mazdutide. That order comes from trial size, design and regulatory status. It is not a recommendation for any person, and it says nothing about which research-grade product is good. We rank evidence here because evidence is the part you can check.

How are these compounds ranked?

We looked for randomized, placebo-controlled human trials published in a peer-reviewed journal, then weighed size, duration and whether the sponsor or an outside group reported the result. Price, availability and popularity played no part. A compound without a comparable published trial that we could open and verify is not ranked. Every figure below is a trial's reported mean percent change in body weight, and each comes from the paper's own abstract unless noted.

Which compounds have the strongest evidence?

Tirzepatide and semaglutide share the top tier because each has a large, double-blind, 68 to 72 week phase 3 trial in people without diabetes, and each reached FDA approval for chronic weight management. In the one trial that compared them directly, tirzepatide came out ahead: -20.2% against -13.7% at 72 weeks. We cover that result and its limits in our head-to-head breakdown.

Even in this tier, caution applies. Gastrointestinal events were the most common adverse events in both programs. In SURMOUNT-1, adverse events led to discontinuation in 4.3% to 7.1% of tirzepatide participants versus 2.6% on placebo. In STEP 1, 4.5% of semaglutide participants stopped treatment for gastrointestinal reasons versus 0.8% on placebo.

How far along are retatrutide and mazdutide?

Retatrutide targets three receptors (GIP, GLP-1 and glucagon). Its phase 2 trial in NEJM reported -24.2% at 48 weeks in the highest arm, with heart rate rising in a dose-dependent way before declining. Lilly's later phase 3 program has reported larger numbers: in TRIUMPH-1, 2,339 participants lost 28.3% at 80 weeks in the highest arm against 2.2% on placebo, according to the sponsor's results as relayed by HCPLive in May 2026.

The same report lists costs of that depth of effect. Discontinuation because of adverse events was 11.3% in the highest arm versus 4.9% on placebo, and dysesthesia, an abnormal skin sensation, appeared in 12.5% versus 0.9%. Sponsor-reported topline data has not gone through the scrutiny of a peer-reviewed paper, so we treat these numbers as provisional.

Mazdutide, a GLP-1 and glucagon dual agonist, has a peer-reviewed phase 3 in NEJM. GLORY-1 enrolled 610 Chinese adults and reported -14.0% at 48 weeks in the higher arm versus +0.3% on placebo. Because every participant was recruited in China, the result may not transfer cleanly to other populations. Innovent Biologics funded it.

Where does tesofensine fit?

Tesofensine is not a peptide and not an incretin. It inhibits the reuptake of noradrenaline, dopamine and serotonin. The Lancet trial found that the 1.0 mg group lost 10.6% more than the group on diet and placebo over 24 weeks. Heart rate rose by 7.4 beats per minute in the 0.5 mg group (P=0.0001), and the authors said the findings needed confirmation in phase III. We have not found that confirmation, so it sits lower in the order.

Which catalog compounds are not ranked?

AOD-9604 and 5-amino-1MQ appear in the catalog, but we did not find a published placebo-controlled weight-loss trial for either that we could open and verify during this review. That is a statement about our search, not proof that no data exists. Until we can cite a trial, we do not rank them or quote weight figures for them. Their profiles describe what the available research covers.

What does a trial ranking mean for research-grade material?

Trial results describe the study drug as manufactured, controlled and dosed under a protocol. They do not describe a vial from any supplier. The FDA's page on unapproved GLP-1 drugs, dated October 1, 2026, warns about products falsely labeled as being for research purposes or not for human consumption that are sold for human use. On this site, research-grade compounds are laboratory materials. Anyone who wants weight management should speak to a physician about approved options.

Bottom line

Evidence order today: tirzepatide and semaglutide, then retatrutide and mazdutide, then older or smaller data such as tesofensine, with other compounds unranked until their trials can be sourced. We update this page when new results or approvals appear. To see what each research-grade compound costs per milligram, use the price comparison table.