Evidence
Every Pivotal GLP-1 Trial, in One Table
I could not find a single place that laid out what each of these trials actually studied, in whom, for how long, and what it found. So I built one. Fourteen trials, compiled from the primary publications and kept current.
This piece exists because of a specific frustration.
Almost every article written about these drugs quotes one number from one trial, without saying which trial, in whom, for how long, or against what. The number then travels. It gets compared to a number from a different trial in a different population, and a conclusion gets drawn that the underlying data does not support.
I could not find a single place that laid out the primary evidence base in one view. So I built one, from the primary publications rather than from secondary coverage, and I intend to keep it current as trials read out. Every row links to the paper.
How to read this table
Three warnings before the data, because a table invites exactly the misuse I am trying to prevent.
Do not compare percentages across rows. Populations differ. Durations differ. Comparators differ. The lifestyle intervention given to both arms differs. Cross-trial comparison is precisely how the field spent three years confidently ranking two drugs that nobody had actually compared.
Diabetes status changes the answer. Across every drug studied, mean weight loss is several percentage points lower in people with type 2 diabetes than in people without it. This is a consistent, replicated finding and it is not a failure of effort.
Mean is not median and neither is you. These are averages across wide distributions. In every one of these trials there were participants who lost more than 25% and participants who lost under 5%.
Weight-loss trials
| Trial | Drug and dose | Population | n | Duration | Mean weight change | Comparator arm |
|---|---|---|---|---|---|---|
| STEP 1 (2021) | Semaglutide 2.4 mg | Overweight/obesity, no diabetes | 1,961 | 68 wk | −14.9% | −2.4% placebo |
| STEP 2 (2021) | Semaglutide 2.4 mg | Overweight/obesity + T2D | 1,210 | 68 wk | −9.6% | −3.4% placebo |
| STEP 3 (2021) | Semaglutide 2.4 mg + intensive behavioural therapy | Overweight/obesity, no diabetes | 611 | 68 wk | −16.0% | −5.7% placebo |
| STEP 4 (2021) | Semaglutide 2.4 mg, randomised withdrawal after 20-wk run-in | Overweight/obesity | 803 | 68 wk | −7.9% further | +6.9% on placebo |
| STEP 8 (2022) | Semaglutide 2.4 mg vs liraglutide 3.0 mg | Overweight/obesity, no diabetes | 338 | 68 wk | −15.8% | −6.4% liraglutide |
| SURMOUNT-1 (2022) | Tirzepatide 5 / 10 / 15 mg | Obesity, no diabetes | 2,539 | 72 wk | −15.0% / −19.5% / −20.9% | −3.1% placebo |
| SURMOUNT-2 (2023) | Tirzepatide 10 / 15 mg | Obesity + T2D | 938 | 72 wk | −12.8% / −14.7% | −3.2% placebo |
| SURMOUNT-4 (2024) | Tirzepatide, randomised withdrawal after 36-wk lead-in | Obesity, no diabetes | 670 | 52 wk randomised | −5.5% further | +14.0% on placebo |
| SURMOUNT-5 (2025) | Tirzepatide vs semaglutide 2.4 mg, both to max tolerated dose | Obesity, no diabetes | 751 | 72 wk | −20.2% | −13.7% semaglutide |
Outcome trials
These are the ones that matter most and get discussed least. They measured events and function, not body weight.
| Trial | Drug | Population | n | Duration | Primary finding |
|---|---|---|---|---|---|
| SUSTAIN-6 (2016) | Semaglutide 0.5 / 1.0 mg | T2D at high cardiovascular risk | 3,297 | 104 wk | MACE hazard ratio 0.74 |
| SELECT (2023) | Semaglutide 2.4 mg | Established CVD + overweight/obesity, no diabetes | 17,604 | ~40 mo median | MACE hazard ratio 0.80 |
| STEP-HFpEF (2023) | Semaglutide 2.4 mg | Heart failure with preserved EF + obesity | 529 | 52 wk | Large improvement in symptom and physical-limitation score |
| FLOW (2024) | Semaglutide 1.0 mg | T2D + chronic kidney disease | 3,533 | ~3.4 yr median | Kidney composite hazard ratio 0.76 |
| SURMOUNT-OSA (2024) | Tirzepatide | Moderate-to-severe OSA + obesity | 469 | 52 wk | Large reduction in apnea-hypopnea index |
What the table shows that the headlines don’t
The diabetes gap is consistent and large. Semaglutide: 14.9% without diabetes, 9.6% with. Tirzepatide: 20.9% without, 14.7% with. Same drugs, same doses, roughly a third less weight loss. The most likely explanations are concurrent medications that promote weight gain, differences in insulin dynamics, and longer disease duration. If you have type 2 diabetes, the honest expectation to set is the second number, not the first.
Behavioural intensity moves the placebo arm more than the drug arm. Compare STEP 1 with STEP 3. The semaglutide arms differ by about a point — 14.9% against 16.0%. The placebo arms differ by more than double, 2.4% against 5.7%, because STEP 3 gave both groups intensive behavioural therapy. What you do alongside the drug matters, and it matters most for the part the drug is not doing.
Withdrawal reverses the result on a predictable timescale. STEP 4 and SURMOUNT-4 are the same experiment run on two molecules, and they agree. Continuing produces further loss; stopping produces regain of a large share of what was lost. I have written about what that means for planning at length.
One head-to-head trial exists. Exactly one. Everything else you have read comparing these two drugs is inference across trials, and inference across trials is how you get confident wrong answers.
What is not in this table
I want to be explicit about the gaps, because a table like this reads as more complete than the evidence actually is.
- No trial here ran beyond about four years. These are drugs many people will take for decades. We do not have decade-scale data.
- Bone mineral density is not a reported endpoint in any of these trials in a way that answers the question people are starting to ask.
- Adolescents, older adults, and people with significant psychiatric histories are under-represented or absent.
- Head-to-head comparisons of the outcome trials do not exist. Tirzepatide’s cardiovascular outcomes trial has not read out. When it does, the second table changes.
- Compounded formulations appear in none of this. The trials studied specific FDA-approved products at specific doses.
Before you use this table
A table of results is only as useful as your ability to interpret it. Relative and absolute risk are different claims, surrogate endpoints are not outcomes, and who was in the trial decides who the finding describes — how to read a GLP-1 study covers the six checks worth applying to every row below. What the accumulated follow-up does and does not establish is in what we know about long-term safety.
Maintenance and corrections
This table is compiled from the primary publications, not from press releases or secondary coverage, and I have linked every source so you can check my transcription against the paper. If you find an error, please email me and I will correct it and date the correction at the top.
It will be updated as trials read out. The next entries I expect to add are tirzepatide’s cardiovascular outcomes data and the oral formulations now in late-stage development.
Questions I get about this month
- How much weight do people lose on semaglutide in clinical trials?
- In STEP 1, adults with overweight or obesity and without diabetes lost a mean of 14.9% of body weight over 68 weeks on semaglutide 2.4 mg, against 2.4% on placebo. In STEP 2, adults who also had type 2 diabetes lost 9.6% over the same period. In STEP 3, where the drug was paired with intensive behavioural therapy, the figure was 16.0%. The population studied changes the answer substantially, which is why a single number quoted without its trial is not very informative.
- How much weight do people lose on tirzepatide in clinical trials?
- In SURMOUNT-1, adults with obesity and without diabetes lost a mean of 15.0%, 19.5%, and 20.9% of body weight at 72 weeks on 5 mg, 10 mg, and 15 mg respectively, against 3.1% on placebo. In SURMOUNT-2, in adults who also had type 2 diabetes, the figures were 12.8% and 14.7%. In the head-to-head SURMOUNT-5 trial, tirzepatide produced 20.2% against semaglutide's 13.7% over 72 weeks.
- Which GLP-1 trials measured outcomes other than weight?
- SELECT measured major adverse cardiovascular events in adults with cardiovascular disease and overweight or obesity without diabetes, and found a 20% relative reduction. SUSTAIN-6 measured the same endpoint in type 2 diabetes. FLOW measured kidney disease progression in type 2 diabetes with chronic kidney disease. STEP-HFpEF measured symptoms and physical limitation in heart failure with preserved ejection fraction. SURMOUNT-OSA measured the apnea-hypopnea index in obstructive sleep apnea. These are the trials that establish clinical benefit rather than surrogate change.
- Can you compare weight loss percentages between different GLP-1 trials?
- Not reliably. Trials differ in the population enrolled, the presence or absence of type 2 diabetes, trial duration, the intensity of the lifestyle intervention given to both arms, the definition of the analysis population, and the era in which they ran. Cross-trial comparison is why tirzepatide appeared superior to semaglutide for three years before anyone had actually compared them; when SURMOUNT-5 finally did, the difference was real but smaller than the naive comparison implied.
Sources
- 01Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). NEJM, 2021.
- 02Davies M et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity and type 2 diabetes (STEP 2). Lancet, 2021.
- 03Wadden TA et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy (STEP 3). JAMA, 2021.
- 04Rubino D et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance (STEP 4). JAMA, 2021.
- 05Rubino DM et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight (STEP 8). JAMA, 2022.
- 06Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). NEJM, 2022.
- 07Garvey WT et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2). Lancet, 2023.
- 08Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction (SURMOUNT-4). JAMA, 2024.
- 09Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). NEJM, 2025.
- 10Lincoff AM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). NEJM, 2023.
- 11Marso SP et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). NEJM, 2016.
- 12Perkovic V et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW). NEJM, 2024.
- 13Kosiborod MN et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (STEP-HFpEF). NEJM, 2023.
- 14Malhotra A et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). NEJM, 2024.
Elise Hall, MD
Board-certified internist in Los Angeles, twenty-one years in practice. She writes about GLP-1 medications and metabolic health for people who want the reasoning, not just the conclusion — and publishes her own year on one of these drugs alongside it.
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