Semaglutide vs Retatrutide
It is the shot behind Ozempic and Wegovy, used for diabetes and weight loss. Trials in tens of thousands of people show about 15% weight loss and fewer heart attacks. A weekly weight-loss injection not yet approved. In trials people lost up to about a quarter of their body weight in 48 weeks.
Semaglutide has the stronger evidence, grade A (strong human evidence) against grade B for Retatrutide. Semaglutide: FDA approved. Retatrutide: In clinical trials.
Evidence
AStrong human evidence
BSome human evidence
Human studies cited
Animal or cell studies cited
Why the grade
Semaglutide has one of the largest trial programs of any peptide: the STEP trials in obesity (STEP 1, 1,961 adults), the SUSTAIN trials in type 2 diabetes, SELECT (17,604 adults with cardiovascular disease and obesity, the largest), FLOW in kidney disease, and systematic reviews pooling tens of thousands of participants. Weight loss, glucose lowering and reductions in heart attack, stroke and kidney outcomes are all shown in randomized placebo-controlled trials. What remains open is what happens over decades and how to stop without regaining.
There is one published randomized phase 2 trial in obesity (338 adults, 48 weeks), a 98-person liver fat substudy of that trial, and one published phase 3 trial, TRIUMPH-2, in 1,152 adults with obesity and type 2 diabetes over 80 weeks; other phase 3 results exist only as press releases. Multiple randomized trials point the same way, but the drug is not approved, most of the roughly 5,800-person TRIUMPH program is unpublished, and there is no long-term safety data, so the grade is B and not A.
FDA
FDA approved
Semaglutide is FDA-approved as Ozempic (weekly injection, type 2 diabetes, 2017; with later indications to reduce cardiovascular events and, since January 2025, kidney disease progression in type 2 diabetes), Rybelsus (daily tablet, type 2 diabetes, 2019), and Wegovy (weekly injection, chronic weight management, 2021; cardiovascular risk reduction in obesity, 2024; MASH with liver fibrosis, 2025; an oral Wegovy tablet, December 2025). Compounded semaglutide is not FDA-approved.
In clinical trials
Retatrutide is an investigational drug and is not approved by the FDA for any use. Eli Lilly has said it plans to file for approval in the first quarter of 2027 after completing manufacturing data. Vials sold online as retatrutide are not a legal product; the FDA has stated that unapproved GLP-1 class drugs cannot be used in compounding.
Sold for
Semaglutide is the GLP-1 injection behind Ozempic and Wegovy, the most talked-about weight loss drug of the decade.
Retatrutide is talked about as the next step beyond tirzepatide, a triple-hormone injection that produced the largest weight loss yet seen in a drug trial.
Studies say
Randomized trials in tens of thousands of people show about 15 percent weight loss, roughly a 1 to 2 point HbA1c reduction, a 20 percent cut in major cardiovascular events and slower kidney decline, with gastrointestinal side effects and weight regain after stopping as the main caveats.
Randomized trials show about a quarter of body weight lost over 48 weeks and roughly a fifth over 80 weeks in people with diabetes, with gastrointestinal side effects and heart rate increases, which supports a B pending approval and full phase 3 publication.
Class
GLP-1 receptor agonist
Triple GLP-1 / GIP / glucagon agonist
Route
Several routes
Injection