Most of what you read about GLP-1 medications is either a sales pitch or a scare story. The actual evidence is more useful than both. Below are the six published studies that shaped how these medications are prescribed today, with the real numbers and the fine print that usually gets left out.

One thing to know up front: every trial here tested the FDA-approved, brand-name versions of these medications, at specific doses, in people who also received diet and activity support. Keep that in mind as you read. We come back to why it matters at the end.

Clinician reviewing notes on a clipboard beside a medication bottle

The short version

Study What it tested Length Average weight change
STEP 1 (2021) Semaglutide 2.4 mg vs. placebo 68 weeks -14.9% vs. -2.4%
SURMOUNT-1 (2022) Tirzepatide 5, 10, 15 mg vs. placebo 72 weeks -15.0%, -19.5%, -20.9% vs. -3.1%
SURMOUNT-5 (2025) Tirzepatide vs. semaglutide 72 weeks -20.2% vs. -13.7%

STEP 1: the semaglutide trial that started it

STEP 1 enrolled 1,961 adults without diabetes who had a BMI of 30 or higher, or 27 or higher with a weight-related condition. Two-thirds received once-weekly semaglutide 2.4 mg and one-third received placebo. Everyone got lifestyle counseling.

After 68 weeks, the semaglutide group had lost an average of 14.9% of their body weight, compared with 2.4% on placebo. Looking at it by threshold:

The fine print: those are averages. Roughly one in seven people on semaglutide did not reach even 5%. Nausea and diarrhea were the most common side effects, mostly mild to moderate, and 4.5% of the semaglutide group stopped treatment because of digestive side effects, compared with 0.8% on placebo.

SURMOUNT-1: tirzepatide at three doses

SURMOUNT-1 followed 2,539 adults with the same eligibility criteria, again excluding diabetes, for 72 weeks. Participants received tirzepatide at 5 mg, 10 mg, or 15 mg weekly, or placebo.

Average weight loss was 15.0% at 5 mg, 19.5% at 10 mg, and 20.9% at 15 mg, compared with 3.1% on placebo. At the two higher doses, about half of participants or more lost at least 20% of their body weight (50.1% and 56.7%), compared with 3.1% on placebo.

The fine print: side effects were mostly mild-to-moderate digestive symptoms during the weeks when doses were being stepped up. Between 4.3% and 7.1% of people on tirzepatide stopped because of side effects, compared with 2.6% on placebo.

SURMOUNT-5: the head-to-head

Comparing STEP 1 to SURMOUNT-1 directly isn't quite fair, because they were different trials with different people. SURMOUNT-5 settled the question by putting the two medications against each other: 751 adults with obesity and without diabetes, each taken to the highest dose they could tolerate, for 72 weeks.

Tirzepatide produced an average weight loss of 20.2%, compared with 13.7% for semaglutide. Waist circumference fell by 18.4 cm versus 13.0 cm.

The fine print: the trial was open-label, meaning participants knew which medication they were taking, and it was funded by tirzepatide's manufacturer. The result is still considered solid, but it's context worth having. "More weight loss on average" also doesn't mean "better for you." Tolerability, medical history, and your prescriber's judgment all factor into which medication fits.

What happens when you stop

Two studies looked at this directly, and they are the ones we most want patients to read.

STEP 1 extension. Researchers followed a group of STEP 1 participants for a year after the medication and the lifestyle support both ended. On average, they regained about two-thirds of the weight they had lost, finishing roughly 5 to 6% below where they started. Improvements in blood pressure and blood sugar markers also drifted back toward baseline.

SURMOUNT-4. Everyone took tirzepatide for 36 weeks. Then 670 participants were randomly assigned to continue or to switch to placebo without knowing which. Over the next year, the group that continued lost a further 5.5% of their body weight. The group switched to placebo regained 14.0%.

What this means: these medications treat appetite and metabolism while you're taking them. They are not a one-time fix. That isn't a reason to avoid them, but it is a reason to go in with a plan for nutrition, muscle, and what long-term looks like, agreed with your prescriber.

Beyond the scale: the SELECT trial

SELECT asked a different question: does this affect the outcomes that matter most? It followed 17,604 adults aged 45 and older who had a BMI of 27 or higher and existing cardiovascular disease, but not diabetes, for an average of about 40 months.

Major cardiovascular events (heart attack, stroke, or cardiovascular death) occurred in 6.5% of the semaglutide group and 8.0% of the placebo group, a 20% relative reduction.

The fine print: this was a specific, higher-risk population. It does not tell us the same benefit applies to a healthy 35-year-old. And 16.6% of the semaglutide group stopped treatment because of side effects, compared with 8.2% on placebo.

The muscle question

Whenever you lose a significant amount of weight, by any method, some of it is lean mass rather than fat. GLP-1 medications are no exception. This is why protein intake and resistance training are part of the conversation from day one, and not something to bolt on later.

Woman doing strength training with light dumbbells at home

What the trials can't tell you

Where we come in

Elemental's GLP-1 program starts with a private consult with our registered nurse, followed by an independent evaluation with a licensed prescriber who decides whether a medication is appropriate for you. If you'd like to see how it runs, read about our nurse-led program or the six questions to ask any provider.

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Sources

This article is general education, not medical advice, and is not a substitute for an evaluation by a licensed prescriber. Elemental does not guarantee that any medication will be prescribed. Individual results vary.