Retatrutide TRIUMPH-1: What NEJM Actually Reported
TRIUMPH-1, the phase 3 obesity trial in adults without diabetes, is now peer-reviewed, published the same day as TRIUMPH-2 in adults with type 2 diabetes. Its primary result for the 12 mg dose is a 25.0% mean weight loss at 80 weeks. Here is why most posts quote 28.3%, and what the trial did and did not show.
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How It Works
The NEJM paper's intention-to-treat analysis gives mean weight changes of −17.6% (4 mg), −23.7% (9 mg) and −25.0% (12 mg) versus −3.9% on placebo at 80 weeks (PMID 42814954). Lilly's topline efficacy-estimand figures for the same arms are −19.0%, −25.9% and −28.3% versus −2.2% (Lilly topline release, May 21, 2026). The efficacy estimand assumes people stayed on treatment, so it runs higher.
In the 574 participants with knee osteoarthritis, WOMAC pain scores fell by 3.4, 3.9 and 4.1 points on 4, 9 and 12 mg versus 2.5 points on placebo (intention-to-treat). The differences versus placebo for 9 and 12 mg were −1.4 and −1.6 points, both P<0.001 (PMID 42814954).
In the 243 participants with obstructive sleep apnea, the apnea-hypopnea index fell by 22.8, 34.3 and 32.1 events per hour on 4, 9 and 12 mg versus 9.6 on placebo (intention-to-treat). The differences for 9 and 12 mg were −24.7 and −22.5 events per hour, both P<0.001 (PMID 42814954).
Retatrutide adds glucagon-receptor agonism to GIP and GLP-1 (PMID 42814954). In separate human physiology studies that did not use retatrutide, a glucagon infusion raised energy expenditure by about 15% in healthy men (PMID 26434748), and a physiological rise in glucagon increased liver mitochondrial oxidation by 50–75% (PMID 39197461). TRIUMPH-1 compared retatrutide only with placebo, so it cannot say how much of the weight loss comes from the glucagon component.
What the Data Shows
Key Takeaways
- TRIUMPH-1 randomized 2,339 adults with obesity and without diabetes to weekly retatrutide 4, 9 or 12 mg or placebo for 80 weeks (PMID 42814954).
- Intention-to-treat mean weight change was −17.6%, −23.7% and −25.0% versus −3.9% on placebo; P<0.001 for 9 and 12 mg (PMID 42814954).
- The widely quoted 28.3% is Lilly's efficacy-estimand figure for 12 mg (Lilly topline release, May 21, 2026), not the NEJM paper's intention-to-treat result.
- Knee osteoarthritis pain and sleep-apnea severity both improved significantly versus placebo on 9 and 12 mg (PMID 42814954).
- In adults with obesity and type 2 diabetes (TRIUMPH-2, 1,152 people), weight loss was smaller: −11.9%, −16.8% and −18.8% versus −5.1% on placebo at 80 weeks (PMID 42810372).
- Gastrointestinal events were the most common side effects (PMID 42814954). In TRIUMPH-2, diarrhoea hit 34% and nausea 28% on 12 mg versus 13% and 8% on placebo, and hypotension and dysesthesia were more frequent on retatrutide (PMID 42810372).
- The phase 3 results are in line with phase 2, where 12 mg produced −24.2% at 48 weeks in a much smaller trial of 338 adults (PMID 37366315).
- How much of the weight loss comes from glucagon agonism specifically. TRIUMPH-1 had no GIP/GLP-1-only comparison arm (PMID 42814954).
- How retatrutide compares head-to-head with tirzepatide or semaglutide. TRIUMPH-1 was placebo-controlled (PMID 42814954).
- How much of the weight lost was lean mass. Body composition is not reported in the TRIUMPH-1 abstract (PMID 42814954).
- Whether retatrutide lowers heart attacks or strokes. TRIUMPH-1 measured weight, knee pain and sleep apnea, not cardiovascular events (PMID 42814954).
- What happens to weight after stopping. The published results cover the on-study period (PMID 42814954).
- Whether the glucagon-infusion findings (higher energy expenditure, higher liver mitochondrial oxidation) carry over to retatrutide in people with obesity. Those studies were short physiology experiments (PMID 26434748, PMID 39197461).
Frequently Asked Questions
What did the retatrutide TRIUMPH-1 trial show?
In 2,339 adults with obesity and without diabetes, weekly retatrutide for 80 weeks produced mean weight changes of −17.6% (4 mg), −23.7% (9 mg) and −25.0% (12 mg) versus −3.9% on placebo (intention-to-treat). It also reduced knee osteoarthritis pain and sleep-apnea events compared with placebo. Gastrointestinal events were the most common side effects (PMID 42814954).
Why do some headlines say 28.3% and others 25%?
They use different estimands from the same trial. The NEJM paper's intention-to-treat (treatment-regimen) analysis gives −25.0% on 12 mg (PMID 42814954). Lilly's topline release (May 21, 2026) led with the efficacy estimand, −28.3%, which estimates the result if everyone had stayed on the drug without starting prohibited weight-loss treatments. Neither is wrong, but the 25.0% figure includes people who stopped treatment.
Did retatrutide help sleep apnea and knee pain in TRIUMPH-1?
Yes. In 243 participants with obstructive sleep apnea, the apnea-hypopnea index fell by 34.3 and 32.1 events per hour on 9 and 12 mg versus 9.6 on placebo. In 574 participants with knee osteoarthritis, WOMAC pain fell by 3.9 and 4.1 points versus 2.5 on placebo. All four comparisons were P<0.001 (intention-to-treat, PMID 42814954).
Does retatrutide work as well in people with type 2 diabetes?
Weight loss was smaller. In TRIUMPH-2 (1,152 adults with obesity and type 2 diabetes), mean weight change at 80 weeks was −11.9%, −16.8% and −18.8% on 4, 9 and 12 mg versus −5.1% on placebo, with improvements in glycaemic control (PMID 42810372).
Does glucagon make retatrutide work better than tirzepatide or semaglutide?
Not shown. It is a plausible idea, not something TRIUMPH-1 tested. Glucagon infusions raised energy expenditure by about 15% in healthy men (PMID 26434748) and increased liver mitochondrial oxidation by 50–75% (PMID 39197461), but those were short physiology studies without retatrutide. TRIUMPH-1 compared retatrutide only with placebo, with no tirzepatide or semaglutide arm (PMID 42814954), so it cannot show that retatrutide outperforms those drugs, let alone why. Social-media claims that retatrutide “beats” other GLP-1 drugs rest on comparing numbers across separate trials with different populations, not on a head-to-head trial.
What side effects showed up in the phase 3 trials?
Gastrointestinal events were the most common in TRIUMPH-1 (PMID 42814954). TRIUMPH-2 gives more detail: diarrhoea in 34% and nausea in 28% on 12 mg versus 13% and 8% on placebo, more hypotension (6% vs under 1%) and dysesthesia (7% vs 1%), and permanent discontinuation due to adverse events or death in 12% on 9 mg and 8% on 12 mg versus 5% on placebo (PMID 42810372).
Is retatrutide approved?
The TRIUMPH-2 paper, published September 2026, describes retatrutide as still under investigation for obesity, type 2 diabetes, knee osteoarthritis and obstructive sleep apnoea (PMID 42810372). Educational purposes only. Not medical advice.
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