GLP-1 Weight Loss: What the Science Actually Shows (SURMOUNT, STEP, SELECT, SURPASS)

GLP-1 medications are backed by some of the strongest weight-management trial data in modern medicine. Because compounded semaglutide and tirzepatide use the same active ingredients studied in those trials, the evidence is worth understanding. Here is what each pivotal study actually showed.

How GLP-1 (and GIP) drugs work

Semaglutide is a GLP-1 receptor agonist — it mimics the GLP-1 gut hormone, slowing gastric emptying, increasing satiety, and improving insulin response. Tirzepatide is a dual GIP/GLP-1 agonist: it adds a second receptor, which appears to amplify the metabolic effect. That mechanistic difference is the leading explanation for why tirzepatide outperforms semaglutide on weight in head-to-head data.

STEP-1: semaglutide for obesity

In STEP-1 (NEJM 2021), adults with obesity and without diabetes received semaglutide 2.4 mg or placebo for 68 weeks alongside lifestyle intervention. The semaglutide group lost about 14.9% of body weight on average, versus 2.4% for placebo. It was the result that launched the modern obesity-medication era.

SURMOUNT-1: tirzepatide raises the ceiling

In SURMOUNT-1 (NEJM 2022), adults with obesity without diabetes received tirzepatide for 72 weeks. At the 15 mg dose, mean weight reduction reached up to about 22.5% (around 20.9% by the more conservative treatment-regimen estimate) — the highest of any FDA-approved weight-management drug studied to date. The 10 mg dose produced about 19.5%.

SURPASS-2: the head-to-head

The cleanest direct comparison is SURPASS-2 (NEJM 2021), in adults with type 2 diabetes. Tirzepatide produced roughly 47% more weight loss than semaglutide 1 mg. While this was a diabetes trial at a lower semaglutide dose, it established tirzepatide’s edge on weight that the obesity trials later reinforced.

SELECT: semaglutide’s cardiovascular trump card

Semaglutide owns one category outright. In the SELECT trial (NEJM 2023), adults with established cardiovascular disease and overweight or obesity (without diabetes) on semaglutide saw about a 20% reduction in major adverse cardiovascular events — heart attack, stroke, cardiovascular death — over roughly three years. Tirzepatide does not yet have an equivalent completed cardiovascular-outcomes trial. If heart-health benefit matters to you, this is the distinguishing evidence.

What this means for compounded products

The molecules in compounded semaglutide and tirzepatide are the same as those studied above. The important caveat: compounded formulations have not been trialed separately, so the trial results describe the molecule and the brand product, not a specific compounded preparation. The pharmacology carries over; the manufacturing quality is provider-dependent, which is why verifying your provider matters.

The honest limitations

• All results required a reduced-calorie diet and increased physical activity. The drugs are tools, not magic.
• Weight regain is common after stopping; these are generally long-term treatments.
• Side effects (nausea, GI upset) are common during titration, and rare serious risks exist — discuss with a clinician.

Choosing a molecule from the evidence

• Maximum weight loss → tirzepatide (SURMOUNT-1, SURPASS-2).
• Cardiovascular benefit → semaglutide (SELECT).
• Cost-sensitive → semaglutide tends to be slightly cheaper compounded.

See the full comparison in semaglutide vs tirzepatide, and the price records on our tirzepatide and semaglutide pages.

Bottom line

The GLP-1 evidence base is real and substantial: tirzepatide leads on weight, semaglutide leads on cardiovascular outcomes, and both far outperform older weight-loss drugs. Compounded versions deliver the same molecules, with the caveat that the formulations themselves aren’t separately trialed.

Educational, not medical advice. Trial figures reflect brand-name product. Compounded medications are not FDA-approved. Consult a licensed clinician.