What the GLP-1 clinical trials actually show
Every major randomized controlled trial behind semaglutide and tirzepatide for weight loss, synthesized in one place — so you can see what's proven, what's still early, and how that should shape which provider and medication you choose.
The trial landscape
Ten trials, spanning weight loss, cardiovascular outcomes, sleep apnea, and liver disease. Every figure below is checked against the published trial or its primary-source press materials — full citations are at the bottom of this page.
| Trial | Drug | N | Duration | Headline result | Source |
|---|---|---|---|---|---|
| STEP 1 | Semaglutide 2.4mg | 1,961 | 68 wks | −14.9% body weight vs −2.4% placebo | Wilding 2021 |
| STEP 4 | Semaglutide 2.4mg (withdrawal design) | 803 | 68 wks (20-wk run-in + 48-wk withdrawal) | Continuers lost a further 7.9%; group switched to placebo regained 6.9% | Rubino 2021 |
| SURMOUNT-1 | Tirzepatide 5/10/15mg | 2,539 | 72 wks | −20.9% (15mg) vs −3.1% placebo (treatment-regimen estimand; −22.5% vs −2.4% under the efficacy estimand) | Jastreboff 2022 |
| SURMOUNT-2 | Tirzepatide 10/15mg, participants with type 2 diabetes | 938 | 72 wks | −13.4% (10mg) / −15.7% (15mg) vs −3.3% placebo | Garvey 2023 |
| SURPASS-2 | Tirzepatide vs semaglutide 1mg, head-to-head, type 2 diabetes population | 1,879 | 40 wks | 86% on tirzepatide 15mg lost ≥5% body weight vs 58% on semaglutide 1mg; 40% vs 9% lost ≥15% | Frías 2021 |
| SELECT | Semaglutide 2.4mg, cardiovascular outcomes | 17,604 | ~40 months | 20% reduction in major adverse cardiovascular events (6.5% vs 8.0%) | Lincoff 2023 |
| SUSTAIN-6 | Semaglutide 0.5/1.0mg, type 2 diabetes, cardiovascular outcomes | 3,297 | 104 wks | 26% reduction in MACE (6.6% vs 8.9%) | Marso 2016 |
| SURMOUNT-OSA | Tirzepatide, obstructive sleep apnea | 469 | 52 wks | AHI reduced 27–29 events/hr vs 5–6 with placebo (~55% relative reduction) | Malhotra 2024 |
| ESSENCE | Semaglutide 2.4mg, MASH / liver fibrosis | 1,197 | 72-wk interim (trial continues to 240 wks) | 62.9% achieved steatohepatitis resolution without worsening fibrosis, vs 34.3% on placebo | Sanyal 2025 |
| OASIS 1 | Oral semaglutide 50mg | 667 | 68 wks | −15.1% body weight vs −2.4% placebo | Knop 2023 |
Note on SURPASS-2 and SURMOUNT-2: both enrolled participants with type 2 diabetes, a population that tends to lose somewhat less weight on GLP-1 therapy than the non-diabetic populations in STEP 1 and SURMOUNT-1 — a real difference in trial population, not a weaker drug effect.
Weight loss by trial, visualized
Mean body-weight reduction from baseline at the highest studied dose, active drug vs. placebo, across the four trials with a directly comparable percentage.
What this means in plain language
Tirzepatide vs. semaglutide isn't just "which loses more weight"
Tirzepatide's dual GLP-1/GIP mechanism is associated with larger average weight reduction than semaglutide in the SURPASS-2 head-to-head trial — but individual response varies a lot, and semaglutide has a longer track record, including cardiovascular-outcomes data (SELECT) that tirzepatide doesn't yet have published at the same scale. "Which drug loses more weight on average" and "which drug has the most evidence behind it" are two different questions with two different answers.
What happens when you stop is a documented trial finding, not speculation
STEP 4 randomized people who'd already lost weight on semaglutide into either continuing the drug or switching to placebo. The group that stopped regained 6.9% of their body weight over the next 28 weeks, while the group that continued lost a further 7.9%. Most provider marketing omits this — it's a real finding from a real trial, and it should factor into how you think about committing to treatment, not just starting it.
SELECT and SUSTAIN-6 matter beyond the scale
Weight loss headlines get the attention, but SELECT and SUSTAIN-6 are about something else: whether the drug reduces heart attacks, strokes, and cardiovascular death. SELECT is the more notable of the two because it enrolled people who were overweight or obese but did not have diabetes — a much broader population than most GLP-1 trials — and still showed a 20% reduction in major cardiovascular events. That's a real differentiator for semaglutide that most comparison sites don't explain clearly.
Decision framework: if you care about X, here's what the evidence says
| Your priority | What the evidence supports |
|---|---|
| Maximum average weight loss | Tirzepatide — SURMOUNT-1 and the SURPASS-2 head-to-head trial both show larger reductions than semaglutide at the doses studied. |
| Longest safety track record | Semaglutide — the deepest trial history in the class, from SUSTAIN-6 (2016) through SELECT (2023). |
| Cardiovascular risk reduction specifically | Semaglutide (SELECT) — the only published GLP-1 cardiovascular-outcomes trial in a primarily non-diabetic population. |
| Avoiding injections | Oral semaglutide (OASIS 1) is real evidence, but a smaller and newer base than the injectable trials — grade it Moderate confidence, not High. |
| Sleep apnea as a specific concern | Tirzepatide (SURMOUNT-OSA) — the only GLP-1/GIP trial designed specifically around OSA severity. |
| Liver disease (MASH) as a specific concern | Semaglutide (ESSENCE) — early but positive histological data; the trial is still ongoing to 240 weeks. |
| Understanding what happens if you stop | STEP 4 is the specific trial to know — weight regain after stopping is documented, not speculation. |
How this should shape which provider you choose
Every trial above tested an FDA-approved branded medication — Wegovy, Ozempic, Zepbound, Mounjaro, or Rybelsus — at a specific, controlled dose. None of them tested a compounded formulation. That matters because a growing share of telehealth GLP-1 providers dispense compounded semaglutide or tirzepatide, made by a compounding pharmacy rather than the original manufacturer, usually at a lower cash price.
We do not claim compounded products are "clinically equivalent" to the trial-tested branded product — that specific claim is what's currently drawing FDA and legal scrutiny industry-wide, including active litigation between GLP-1 manufacturers and telehealth providers over how compounded products are marketed. The active ingredient may be the same; the trial evidence above applies to the branded product that was actually studied, not to a compounded version of it.
| Provider | What it primarily prescribes | Tier |
|---|---|---|
| Ro | Predominantly FDA-approved branded GLP-1s (Wegovy, Zepbound, Ozempic), with insurance/prior-auth coordination for brand coverage. | Branded-primary |
| LifeMD | Brand-name GLP-1 access as its core positioning. | Branded-primary |
| WeightWatchers Clinic | Brand-name only, bundled with WeightWatchers' coaching program. | Branded-primary |
| Found | Both compounded semaglutide and brand-name options (including Zepbound), through 503A/503B compounding pharmacies. | Mixed |
| Noom Med | Both compounded semaglutide and brand-name GLP-1s (Wegovy, Zepbound, Ozempic, oral Wegovy), depending on the plan. | Mixed |
| Mochi Health | Both, with compounded semaglutide as its primary, lower-cost tier. | Mixed |
| Henry Meds | Compounded medication only (injectable/sublingual semaglutide, oral tirzepatide) — does not dispense branded Wegovy, Ozempic, Mounjaro, or Zepbound. Subject to active litigation over compounded-tirzepatide marketing, unresolved as of this writing. | Compounded-primary |
| Calibrate | Formulation mix not independently confirmed for this page — ask directly before enrolling. | Unconfirmed |
| TrimRx | Both compounded semaglutide/tirzepatide and brand-name options (Ozempic, Mounjaro, Zepbound, Wegovy). | Mixed |
| Medvi | Both compounded and FDA-approved branded GLP-1s. Received an FDA warning letter in February 2026 over labeling that implied Medvi itself was the compounding pharmacy. | Mixed |
| AltRx | Both compounded semaglutide/tirzepatide and all four brand-name GLP-1s. Parent company Trinity Healthcare Supply received an FDA warning letter in June 2026 over website claims and labeling. | Mixed |
| DirectMeds | Compounded semaglutide/tirzepatide as its primary offering; LegitScript-certified. | Compounded-primary |
| Embody | Compounded medication only (semaglutide, tirzepatide) — does not dispense branded product. | Compounded-primary |
| Trimi | Compounded semaglutide only as of 2026 — no branded options; no longer offers compounded tirzepatide as of April 2026. | Compounded-primary |
Provider formularies change quickly — several telehealth companies shifted their compounded-vs-branded mix during 2026 alone. Confirm what you'd actually be prescribed directly with the provider before enrolling; this table reflects our research as of the "last reviewed" date above, not a live feed of each provider's offerings.
Full citation list
- Wilding JPH, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity" (STEP 1). N Engl J Med. 2021. nejm.org
- Rubino D, et al. "Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity" (STEP 4). JAMA. 2021. jamanetwork.com
- Jastreboff AM, et al. "Tirzepatide Once Weekly for the Treatment of Obesity" (SURMOUNT-1). N Engl J Med. 2022. nejm.org
- Garvey WT, et al. "Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes" (SURMOUNT-2). Lancet. 2023. thelancet.com
- Frías JP, et al. "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes" (SURPASS-2). N Engl J Med. 2021. pubmed.ncbi.nlm.nih.gov
- Lincoff AM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes" (SELECT). N Engl J Med. 2023. pubmed.ncbi.nlm.nih.gov
- Marso SP, et al. "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes" (SUSTAIN-6). N Engl J Med. 2016. nejm.org
- Malhotra A, et al. "Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity" (SURMOUNT-OSA). N Engl J Med. 2024. nejm.org
- Sanyal AJ, et al. "Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis" (ESSENCE). N Engl J Med. 2025. nejm.org
- Knop FK, et al. "Oral semaglutide 50 mg taken once per day in adults with overweight or obesity" (OASIS 1). Lancet. 2023. pubmed.ncbi.nlm.nih.gov
See how all 14 providers score
Every provider scored out of 10, built from this evidence — plus independent rating, insurance support, and regulatory standing.
View the scores