Tirzepatide SURMOUNT Trials: Complete Analysis
The SURMOUNT program is the clinical trial backbone behind [tirzepatide](/peptides/tirzepatide-dual-gipglp-1-agonist-profile/) (marketed as Zepbound for weight management and Mounjaro for type 2 diabetes).
The SURMOUNT program is the clinical trial backbone behind tirzepatide (marketed as Zepbound for weight management and Mounjaro for type 2 diabetes). Unlike semaglutide, which targets a single receptor, tirzepatide is a dual GIP/GLP-1 receptor agonist --- the first approved drug to activate both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) pathways simultaneously.
That dual mechanism appears to matter. The SURMOUNT trials produced weight-loss numbers that exceed anything seen with single-receptor GLP-1 drugs, including semaglutide. This article walks through each trial in the program --- study designs, participant data, outcomes, side effects, and what the results actually tell us about tirzepatide's place in obesity treatment.
Table of Contents
- Understanding the SURMOUNT Program
- SURMOUNT-1: The Foundational Trial
- SURMOUNT-2: Weight Loss With Type 2 Diabetes
- SURMOUNT-3: After Intensive Lifestyle Intervention
- SURMOUNT-4: Withdrawal and Weight Regain
- SURMOUNT-5: Head-to-Head Against Semaglutide
- SURMOUNT-OSA: Obstructive Sleep Apnea
- SURMOUNT-MMO: The Cardiovascular Outcomes Trial
- Cross-Trial Comparison Table
- Limitations Worth Noting
- FAQ
- The Bottom Line
- References
Understanding the SURMOUNT Program
All SURMOUNT trials tested subcutaneous tirzepatide administered once weekly. Most trials tested three doses: 5 mg, 10 mg, and 15 mg (or the maximum tolerated dose, which was typically 10 or 15 mg). Each trial included a 20-week dose-escalation period where the dose was gradually increased to reduce GI side effects.
The program was sponsored by Eli Lilly. Like any industry-sponsored trial program, that fact doesn't disqualify the data, but it's context worth keeping in mind. The trials were published in peer-reviewed journals including the New England Journal of Medicine, The Lancet, JAMA, and Nature Medicine.
The central question the SURMOUNT program answered: does activating both GIP and GLP-1 receptors produce better results than GLP-1 alone? Based on the data, the answer appears to be yes.
SURMOUNT-1: The Foundational Trial
Published in the New England Journal of Medicine in July 2022, SURMOUNT-1 was the trial that established tirzepatide as a weight-loss drug capable of producing surgical-level results with a weekly injection [1].
Study Design
- Population: 2,539 adults with BMI of 30+ (or 27+ with at least one weight-related complication), without diabetes
- Randomization: 1:1:1:1 to tirzepatide 5 mg, 10 mg, 15 mg, or placebo
- Duration: 72 weeks (including 20-week dose escalation)
- Primary endpoints: Percentage change in body weight; proportion achieving at least 5% weight loss
Results
| Outcome | 5 mg | 10 mg | 15 mg | Placebo |
|---|---|---|---|---|
| Mean weight loss (efficacy estimand) | -16.0% | -21.4% | -22.5% | -2.4% |
| Mean weight loss (treatment-regimen estimand) | -15.0% | -19.5% | -20.9% | -3.1% |
| Achieved 5%+ loss | 85.1% | 88.9% | 90.9% | 34.5% |
| Achieved 20%+ loss | 16.5% | 36.2% | 39.7% | 1.5% |
| Achieved 25%+ loss | 15.3% | 32.3% | 36.2% | 1.5% |
At the 15 mg dose, participants lost an average of 52 pounds (24 kg) from a baseline weight of about 231 pounds (104.8 kg) [1].
Body Composition
An important sub-analysis showed that the weight loss was disproportionately from fat: participants lost approximately 33.9% of their fat mass versus 10.9% of their lean mass. That roughly 3:1 ratio is more favorable than what's typically seen with caloric restriction alone [1].
Safety
GI adverse events were the most common side effects, consistent with other incretin-based drugs. These were mostly mild to moderate and clustered during the dose-escalation phase. Discontinuation rates due to adverse events were low across all dose groups [1].
What This Means
SURMOUNT-1 set a new bar. The 22.5% mean weight loss at the highest dose exceeded anything seen in the STEP trials for semaglutide (14.9% in STEP 1). And the consistency across dose groups --- even the lowest 5 mg dose produced 16% weight loss --- suggested robust efficacy across a range of exposures.
SURMOUNT-2: Weight Loss With Type 2 Diabetes
Like STEP 2 for semaglutide, SURMOUNT-2 tested whether tirzepatide could produce meaningful weight loss in the harder-to-treat population of people with both obesity and type 2 diabetes [2].
Study Design
- Population: 938 adults with BMI of 27+ and type 2 diabetes (HbA1c 7--10%)
- Randomization: 1:1:1 to tirzepatide 10 mg, 15 mg, or placebo
- Duration: 72 weeks
- Sites: Multiple centers across 7 countries
Results
| Outcome (Efficacy Estimand) | 10 mg | 15 mg | Placebo |
|---|---|---|---|
| Mean weight loss | -13.4% | -15.7% | -3.3% |
| Achieved 5%+ loss | 79% | 83% | 32% |
| HbA1c reaching <5.7% | 46% | 49% | 3% |
For context on cardiometabolic changes: pooled tirzepatide doses showed reductions in systolic blood pressure (-7.2 mmHg vs -1.0 mmHg for placebo), fasting triglycerides (-28.6% vs -5.8%), and HDL cholesterol improvements (+8.2% vs +1.1%) [2].
Safety
GI adverse events were the most frequent side effects, with fewer than 5% of tirzepatide participants discontinuing due to GI symptoms. Two deaths occurred in the 10 mg group (smoke inhalation and cardiorespiratory arrest), neither attributed to the study drug by investigators [2].
What This Means
SURMOUNT-2 produced some of the best weight-loss numbers ever recorded in a population with type 2 diabetes. The 15.7% mean weight loss at the highest dose exceeds the 9.6% seen with semaglutide 2.4 mg in STEP 2 by a wide margin. And the glycemic improvements were striking: nearly half of participants on tirzepatide achieved an HbA1c below 5.7% (the upper limit of normal), essentially reaching non-diabetic glucose levels --- all without any cases of severe hypoglycemia.
For those exploring peptides for diabetes management, these are important numbers.
SURMOUNT-3: After Intensive Lifestyle Intervention
SURMOUNT-3 asked a practical clinical question: if someone first loses weight through intensive lifestyle changes, does adding tirzepatide produce further benefit [3]?
Study Design
- Population: 806 adults with obesity or overweight with comorbidities (no diabetes), started a 12-week intensive lifestyle lead-in
- Lead-in: Low-calorie diet, exercise, and weekly counseling for 12 weeks
- Randomization: 579 participants who achieved at least 5% weight loss during lead-in were randomized 1:1 to tirzepatide (maximum tolerated dose) or placebo for 72 weeks
Results
| Phase | Tirzepatide | Placebo |
|---|---|---|
| Lead-in weight loss (12 weeks) | -6.9% | -6.9% |
| Additional weight change (72 weeks post-randomization) | -18.4% | +2.5% |
| Total weight loss from study entry | -26.6% | ~-4.5% |
The treatment difference from randomization was -20.8 percentage points (95% CI, -23.2 to -18.5; P<0.001). Among tirzepatide participants, 87.5% achieved an additional 5%+ weight loss after randomization, versus 16.5% on placebo [3].
Safety
Nausea (39.7% vs 14.0%), diarrhea (31.0% vs 9.2%), constipation (23.0% vs 6.8%), and vomiting (18.1% vs 1.4%) were more common with tirzepatide. Adverse events led to discontinuation in 10.5% of the tirzepatide group [3].
What This Means
A total weight loss of 26.6% from study entry is remarkable. It suggests that sequential use of lifestyle intervention followed by tirzepatide produces additive results --- you get the benefit of each approach stacked on top of the other. The drug-specific weight loss during the randomized phase (-18.4%) was similar to what tirzepatide achieved in SURMOUNT-1, meaning the prior lifestyle-induced loss didn't reduce the drug's own effectiveness.
However, the higher discontinuation rate (10.5% vs 2.1%) compared to other SURMOUNT trials deserves attention. Starting a GLP-1 drug after weeks of low-calorie dieting may make GI side effects harder to tolerate.
SURMOUNT-4: Withdrawal and Weight Regain
SURMOUNT-4 used a withdrawal design to answer the same question STEP 4 addressed for semaglutide: what happens to weight loss when you stop the drug [4]?
Study Design
- Population: 783 adults with BMI of 30+ (or 27+ with comorbidities), without diabetes
- Phase 1 (open-label): All participants received tirzepatide at maximum tolerated dose (10 or 15 mg) for 36 weeks
- Phase 2 (randomized): 670 participants randomized 1:1 to continue tirzepatide or switch to placebo for 52 weeks
Results
| Phase | Continued Tirzepatide | Switched to Placebo |
|---|---|---|
| Weight loss during 36-week lead-in | -20.9% | -20.9% |
| Weight change during 52-week randomized period | -5.5% (further loss) | +14.0% (regain) |
| Maintained 80%+ of lead-in weight loss at week 88 | ~90% | 16.6% |
The treatment difference was stark: continued treatment produced ongoing weight loss while discontinuation led to regain of roughly two-thirds of the initial loss [4].
Post Hoc Analysis: Cardiometabolic Consequences
A 2025 post hoc analysis published in JAMA Internal Medicine examined 308 participants who lost at least 10% during the lead-in and were switched to placebo [5]:
| Weight Regain Category | Proportion | Cardiometabolic Outcome |
|---|---|---|
| Less than 25% regain | 17.5% | Maintained improvements in most parameters |
| 25--49% regain | 25.0% | Partial reversal, some benefits preserved |
| 50--74% regain | 33.4% | Substantial reversal of initial improvements |
| 75%+ regain | 24.0% | Near-complete return to baseline levels |
One year after stopping tirzepatide, 82.5% of participants had regained at least 25% of their lost weight. Those who regained 75% or more saw their blood pressure, cholesterol, insulin resistance, and other cardiometabolic markers return essentially to pre-treatment levels [5].
What This Means
SURMOUNT-4 delivers the same message as STEP 4 for semaglutide, perhaps even more emphatically: obesity is a chronic condition requiring ongoing treatment. The 14 percentage points of regain in the placebo group versus 5.5 points of further loss in the continuation group creates a 20-point gap over one year. The cardiometabolic post hoc data adds an important layer: it's not just the weight that returns, but the metabolic improvements reverse too. Stopping the drug doesn't just mean a higher number on the scale --- it means returning metabolic risk.
SURMOUNT-5: Head-to-Head Against Semaglutide
This was the trial the field had been waiting for: a direct comparison between tirzepatide and semaglutide. Published in the New England Journal of Medicine in 2025, SURMOUNT-5 was the first randomized head-to-head trial between these two drugs [6].
Study Design
- Population: 751 adults with BMI of 30+ (or 27+ with comorbidities), without diabetes
- Randomization: 1:1 to tirzepatide (maximum tolerated dose of 10 or 15 mg) or semaglutide (maximum tolerated dose of 1.7 or 2.4 mg)
- Duration: 72 weeks
- Design: Open-label (due to different dosing regimens), conducted at 32 sites in the US and Puerto Rico
Results
| Outcome | Tirzepatide | Semaglutide |
|---|---|---|
| Mean weight loss | -20.2% | -13.7% |
| Absolute weight loss | -22.8 kg | -15.0 kg |
| Achieved 10%+ loss | ~80% | ~55% |
| Achieved 25%+ loss | 31.6% | 16.1% |
| Waist circumference reduction | -18.4 cm | -13.0 cm |
The treatment difference was -6.5 percentage points (P<0.001). Tirzepatide provided 47% greater relative weight loss compared to semaglutide [6].
Safety
GI adverse events were common with both drugs. Notably, GI-related discontinuation was higher with semaglutide (5.6%) than tirzepatide (2.7%). Serious adverse events were similar between groups (4.8% tirzepatide vs 3.5% semaglutide) [6].
What This Means
SURMOUNT-5 confirmed what cross-trial comparisons had suggested: tirzepatide produces more weight loss than semaglutide at their respective approved doses. The -20.2% versus -13.7% gap is clinically meaningful --- about 7.8 kg (17 lb) more weight lost.
Two caveats: the trial was open-label, meaning participants and clinicians knew which drug they were receiving, which can influence behavior and reporting. And semaglutide's newer 7.2 mg dose (tested in STEP UP, showing -20.7% weight loss) was not included in this comparison. A head-to-head between tirzepatide 15 mg and semaglutide 7.2 mg remains the study the field still needs.
SURMOUNT-OSA: Obstructive Sleep Apnea
Obesity is the leading risk factor for obstructive sleep apnea (OSA). SURMOUNT-OSA tested whether tirzepatide-driven weight loss could meaningfully reduce sleep apnea severity [7].
Study Design
Two parallel trials under a master protocol:
- Study 1: 234 adults with moderate-to-severe OSA and obesity who were not using positive airway pressure (PAP) therapy
- Study 2: 235 adults with the same profile who were using PAP therapy
- Randomization: 1:1 to tirzepatide (maximum tolerated dose) or placebo
- Duration: 52 weeks
Results
| Outcome | Study 1 (No PAP) | Study 2 (With PAP) |
|---|---|---|
| AHI reduction (tirzepatide) | -25.3 events/hr | -29.3 events/hr |
| AHI reduction (placebo) | -5.3 events/hr | -5.5 events/hr |
| Treatment difference | -20.0 events/hr | -23.8 events/hr |
| AHI reduction (%) | Up to 62.8% | -- |
| Disease resolution criteria met | 43.0% | 51.5% |
Both studies met all primary and key secondary endpoints. Participants also showed reductions in hypoxic burden, hsCRP, systolic blood pressure, and body weight [7].
What This Means
These results have potential implications beyond weight loss. Moderate-to-severe OSA affects roughly 30 million Americans and is linked to cardiovascular disease, stroke, and all-cause mortality. Current treatment relies heavily on PAP machines, which many patients struggle to use consistently. If tirzepatide gains approval for OSA, it would be the first pharmaceutical treatment targeting the underlying condition rather than just the symptoms. For readers interested in the cardiovascular dimensions, see our guide on peptides for cardiovascular health.
SURMOUNT-MMO: The Cardiovascular Outcomes Trial
SURMOUNT-MMO is tirzepatide's answer to semaglutide's SELECT trial --- a massive cardiovascular outcomes study still in progress [8].
Study Design
- Population: Approximately 15,000 adults aged 40+ with BMI of 27+, established cardiovascular disease or multiple cardiovascular risk factors, without diabetes
- Randomization: Tirzepatide versus placebo
- Primary endpoint: Time to first occurrence of a five-component composite: nonfatal MI, nonfatal stroke, coronary revascularization, heart failure events, or death from any cause
- Expected completion: October 2027
- Sites: 664 sites across 27 countries
Why It Matters
SURMOUNT-MMO differs from SELECT in two important ways. First, it includes both primary prevention (people at risk for cardiovascular disease) and secondary prevention (people who already have it). SELECT only studied secondary prevention. Second, its primary endpoint includes heart failure events and coronary revascularization --- broader than SELECT's three-component MACE.
Available Evidence So Far
While SURMOUNT-MMO results aren't available yet, a few data points offer early signals:
- SURPASS-CVOT (in type 2 diabetes): Tirzepatide was noninferior but not superior to dulaglutide for cardiovascular events, with MACE occurring in 12.2% versus 13.1% over 4 years [8].
- Observational studies: Real-world data comparing tirzepatide to GLP-1 receptor agonists has shown favorable trends for MI, stroke, and all-cause mortality (HR 0.60; 95% CI 0.43--0.84) [8].
- SURMOUNT-5 post hoc analysis: Tirzepatide was associated with greater predicted 10-year cardiovascular risk reduction compared to semaglutide [6].
Until SURMOUNT-MMO reports, tirzepatide lacks the dedicated cardiovascular outcomes evidence that semaglutide has from SELECT. This remains one of the most significant evidence gaps between the two drugs.
Cross-Trial Comparison Table
| Trial | N | Population | Duration | Dose(s) Tested | Best Weight Loss | Comparator Result |
|---|---|---|---|---|---|---|
| SURMOUNT-1 [1] | 2,539 | Obesity, no diabetes | 72 wk | 5/10/15 mg | -22.5% (15 mg) | -2.4% (placebo) |
| SURMOUNT-2 [2] | 938 | Obesity + T2D | 72 wk | 10/15 mg | -15.7% (15 mg) | -3.3% (placebo) |
| SURMOUNT-3 [3] | 579* | Obesity + prior ILI | 72 wk | MTD | -18.4% (additional) | +2.5% (placebo) |
| SURMOUNT-4 [4] | 670* | Obesity (withdrawal) | 52 wk** | MTD | -5.5% (further loss) | +14.0% (regain) |
| SURMOUNT-5 [6] | 751 | Obesity vs semaglutide | 72 wk | MTD | -20.2% | -13.7% (semaglutide) |
| SURMOUNT-OSA [7] | 469 | OSA + obesity | 52 wk | MTD | AHI -25 to -29/hr | AHI -5/hr (placebo) |
*Randomized after lead-in. **Post-randomization period. MTD = maximum tolerated dose. ILI = intensive lifestyle intervention. T2D = type 2 diabetes.
Limitations Worth Noting
Industry sponsorship. All SURMOUNT trials were funded by Eli Lilly. The same caveat applies here as with the STEP program --- well-designed trials published in top journals, but funded by the company selling the drug.
Open-label head-to-head. SURMOUNT-5, arguably the highest-impact trial in the program, was open-label. Participants and investigators knew which drug they were receiving. While this was necessary due to different dosing schedules, it introduces the possibility of performance bias.
Dose comparison gap. SURMOUNT-5 compared tirzepatide to semaglutide 2.4 mg, not to the newer 7.2 mg dose. At 7.2 mg, semaglutide achieves about 20.7% weight loss in the on-treatment analysis --- essentially matching tirzepatide. A head-to-head at those doses hasn't been conducted.
Weight regain on discontinuation. SURMOUNT-4 showed the same pattern as STEP 4: stop the drug, and the weight comes back. Over 80% of participants who stopped tirzepatide regained at least a quarter of their lost weight within one year. This positions tirzepatide --- like semaglutide --- as a chronic treatment rather than a time-limited intervention.
Missing cardiovascular outcomes data. Unlike semaglutide, which has the SELECT trial showing a 20% reduction in MACE, tirzepatide lacks a completed cardiovascular outcomes trial in obesity. The SURPASS-CVOT showed noninferiority (but not superiority) to dulaglutide in type 2 diabetes. SURMOUNT-MMO won't report until 2027. For now, the cardiovascular case for tirzepatide relies on biomarker improvements and observational data rather than hard endpoint evidence.
Real-world performance. Clinical trial participants are more adherent and more closely monitored than typical patients. Real-world weight-loss results with tirzepatide will likely be lower than the trial figures, as has been observed with semaglutide.
Limited long-term data. The longest SURMOUNT data extends to about 3 years (from the SURMOUNT-1 extension). Questions about effects over 5, 10, or 20 years of treatment remain unanswered.
FAQ
How much weight loss does tirzepatide produce?
In SURMOUNT-1 (adults without diabetes), the 15 mg dose produced a mean weight loss of 22.5% over 72 weeks --- roughly 52 pounds from a starting weight of about 231 pounds. In people with type 2 diabetes (SURMOUNT-2), the 15 mg dose achieved 15.7%. Individual results vary.
Is tirzepatide better than semaglutide for weight loss?
At currently approved doses, yes. SURMOUNT-5 showed tirzepatide produced -20.2% weight loss versus -13.7% for semaglutide over 72 weeks. However, semaglutide's higher 7.2 mg dose (not yet widely approved) narrows that gap. For more on comparing these medications, see our profiles on semaglutide and tirzepatide.
What makes tirzepatide different from other GLP-1 drugs?
Tirzepatide activates both GIP and GLP-1 receptors, while drugs like semaglutide and liraglutide target only GLP-1. The dual-receptor mechanism appears to produce greater effects on appetite, insulin sensitivity, and energy expenditure. Newer drugs like retatrutide go even further, targeting three receptors simultaneously.
Does tirzepatide reduce cardiovascular risk?
The data so far is encouraging but not definitive. Tirzepatide consistently improves cardiovascular risk factors (blood pressure, lipids, inflammatory markers, blood sugar). Observational data shows favorable trends. But the dedicated cardiovascular outcomes trial (SURMOUNT-MMO) won't report until 2027. Semaglutide currently has stronger cardiovascular evidence from the completed SELECT trial.
What happens if I stop taking tirzepatide?
SURMOUNT-4 showed that participants who stopped tirzepatide regained an average of 14 percentage points of weight over 52 weeks, while those who continued treatment lost an additional 5.5%. The cardiometabolic improvements (blood pressure, cholesterol, insulin sensitivity) also reversed with weight regain.
Can tirzepatide treat sleep apnea?
SURMOUNT-OSA showed that tirzepatide reduced sleep apnea severity by up to 63%, with about half of participants meeting criteria for disease resolution. If approved for this indication, it would be the first pharmaceutical treatment for obstructive sleep apnea. This is especially relevant since OSA affects many people with obesity.
What are the common side effects?
Nausea, diarrhea, constipation, and vomiting are the most reported side effects. They're most common during the dose-escalation phase and tend to improve over time. In SURMOUNT-5, GI-related discontinuation was actually lower with tirzepatide (2.7%) than with semaglutide (5.6%).
How does tirzepatide compare to AOD-9604 or other fat-loss peptides?
The evidence base is not comparable. Tirzepatide has data from thousands of participants across multiple phase 3 trials. Most other peptides discussed in the fat-loss peptide context have far smaller and earlier-stage evidence. Tirzepatide and semaglutide represent the current gold standard for evidence-based peptide weight loss.
The Bottom Line
The SURMOUNT program makes a strong case that tirzepatide's dual GIP/GLP-1 mechanism produces weight loss beyond what single-receptor GLP-1 drugs achieve. Across every trial, the numbers are consistent: 15--22% weight loss in people without diabetes, 13--16% in those with type 2 diabetes, and clinically meaningful improvements in cardiovascular risk factors, sleep apnea, and quality of life.
The head-to-head data from SURMOUNT-5 confirms tirzepatide's advantage over semaglutide at currently approved doses. The SURMOUNT-3 sequential approach --- lifestyle first, then medication --- produced total weight loss of 26.6%, the highest figure in the program.
But the data also draws clear boundaries. Stop the drug, and the weight comes back. GI side effects are common, even if usually manageable. The cardiovascular outcomes story is incomplete until SURMOUNT-MMO reports in 2027. And the comparison with semaglutide's higher 7.2 mg dose remains an unanswered question.
For anyone evaluating tirzepatide, the SURMOUNT trials offer the most complete picture available. They show what the drug can do, under what conditions, and where the evidence runs out. For broader context on how tirzepatide fits into the obesity treatment picture, explore our guides on peptides for obesity and peptide stacking approaches.
References
-
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. PubMed
-
Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-626. PubMed
-
Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909-2918. PubMed
-
Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. PubMed
-
Karagiannis T, Bekiari E, Tsapas A. Cardiometabolic parameter change by weight regain on tirzepatide withdrawal in adults with obesity: a post hoc analysis of the SURMOUNT-4 trial. JAMA Intern Med. 2025. PubMed
-
Aronne LJ, Finer N, Engeli S, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025. PubMed
-
Malhotra A, Grunstein RR, Engeli S, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(14):1288-1298. PubMed
-
Lam CSP, Docherty KF, Ho JE, et al. Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT-MMO trial. Obesity. 2025. PubMed