Is Retatrutide Better Than Semaglutide? The Short Answer

In the first Phase 3 trial to compare them directly, retatrutide lowered blood sugar more and roughly doubled the weight loss of semaglutide in adults with type 2 diabetes. In TRANSCEND-T2D-2, a Phase 3 trial of 1,298 adults, its developer reported these topline results at 80 weeks:

• Weight: 20.9% weight loss on retatrutide 12 mg and 19.5% on 9 mg, against 9.4% on semaglutide 2 mg.
• A1C: a fall of 2.2 percentage points on both retatrutide doses, against 1.8 on semaglutide, from an average of 8.3%.
• Stopping because of side effects: 7.9% on retatrutide 12 mg and 4.8% on 9 mg, against 2.7% on semaglutide.

The results come from the company's October 28, 2026, announcement and use the efficacy estimand, which estimates the effect had everyone stayed on treatment. The full results have not yet been published in a journal. The trial was open-label, it was in people with type 2 diabetes, and the semaglutide dose was 2 mg, the highest approved dose of injectable semaglutide for type 2 diabetes, not the higher doses approved for weight management. Retatrutide is not approved for any use.

What TRANSCEND-T2D-2 Tested

TRANSCEND-T2D-2 is a randomized, open-label Phase 3 trial, which means participants and investigators knew which medicine each person was taking. According to the company's announcement and its medical information page:

• Participants: 1,298 adults with type 2 diabetes not controlled by metformin, with or without an SGLT2 inhibitor, with an A1C of 7.0% to 10.5%.
• Treatments: once-weekly retatrutide 9 mg or 12 mg, or semaglutide 2 mg (Ozempic), assigned in a 2:2:1 ratio, so about 260 people received semaglutide (our calculation). Retatrutide doses were increased step by step to the assigned dose.
• Length: 80 weeks, with about 650 participants continuing retatrutide in a 24-week extension.
• Main question: whether retatrutide 12 mg was noninferior to semaglutide 2 mg in lowering A1C at 80 weeks, meaning not worse by more than a set margin.
• Starting point: average A1C 8.3%, weight 102.4 kg and BMI 36.8.
• Sites: 77 sites in Argentina, Canada, Mexico, Puerto Rico and the United States.

The company describes it as "the first Phase 3 trial comparing retatrutide with another incretin medicine." Until now, comparisons between retatrutide and semaglutide relied on separate trials, as described in retatrutide vs tirzepatide vs semaglutide.

Retatrutide vs Semaglutide: Weight Loss and A1C

On weight, retatrutide 12 mg was ahead of semaglutide by 11.5 percentage points, about 2.2 times the semaglutide result (our calculation). On A1C, both retatrutide doses were 0.4 points ahead. The company reports that both comparisons with 12 mg were statistically significant (p<0.001) under its control for multiple testing. For 9 mg, A1C met noninferiority to semaglutide, a key secondary end point; its larger A1C reduction was significant only nominally, outside that formal control. Both doses also reduced weight significantly more than semaglutide.

The company adds that retatrutide gave greater improvements than semaglutide in non-HDL cholesterol, triglycerides and systolic blood pressure, but gives no figures for them; for 9 mg, the blood pressure difference was significant only nominally. How retatrutide affects blood sugar in other trials is covered in retatrutide for diabetes.

How the Results Were Counted

All results use the efficacy estimand: the estimated effect had all randomized participants stayed on their study drug for 80 weeks without adding other diabetes medicines for more than 14 days. The announcement does not give results counting everyone randomized whether or not they stayed on treatment (the treatment-regimen estimand), which are usually smaller. Why the two differ is explained in why retatrutide weight loss numbers differ.

Side Effects: Retatrutide vs Semaglutide

Gastrointestinal side effects were the most common on retatrutide and were also frequent on semaglutide, at broadly similar rates. Diarrhea and vomiting were most frequent on retatrutide 12 mg, while constipation was more frequent on semaglutide. The largest relative differences were in stopping treatment because of side effects, which was about three times as common on retatrutide 12 mg as on semaglutide, and in dysesthesia, an altered skin sensation covered in dysesthesia from retatrutide. The company says most urinary tract infections and dysesthesia events on retatrutide were mild to moderate and typically resolved during treatment.

The announcement does not give the number of participants behind each percentage, and it does not report serious adverse events or low blood sugar. The wider side-effect profile from the larger trials is in retatrutide side effects.

What This Trial Does and Does Not Show

• It is a direct comparison. Both medicines were tested in the same trial, at the same time, in the same population, which removes the main weakness of earlier comparisons across separate trials.
• It was in type 2 diabetes. In retatrutide's own trials, people with type 2 diabetes lost less weight than people without it: on 12 mg at 80 weeks, on the same efficacy estimand, 20.8% in TRIUMPH-2, a placebo-controlled trial in obesity with type 2 diabetes, against 28.3% in TRIUMPH-1, in obesity without diabetes. The 20.9% here is close to the TRIUMPH-2 figure, so these results should not be read as what retatrutide does in people without diabetes.
• Semaglutide was given at its diabetes dose. The 2 mg dose is the highest approved dose of injectable semaglutide for type 2 diabetes. Semaglutide is approved for weight management at higher doses, such as 2.4 mg, which this trial did not test, so the result does not show how retatrutide compares with those doses.
• It was open-label. Knowing the assigned medicine can influence reporting of side effects and decisions to stop treatment.
• The results are topline. They come from a company announcement, not a peer-reviewed paper; the company says detailed results will be presented at a medical meeting and published.

What Comes Next

The 24-week extension continues for about 650 participants. The company is also comparing retatrutide directly with tirzepatide in TRIUMPH-5, an ongoing Phase 3 trial in adults with obesity with or without type 2 diabetes, which has not reported results.

Retatrutide Sold Online: Why the Trial Data Don't Apply

Retatrutide is not approved and, according to its developer, is legally available only through clinical trials. The company says anything sold to consumers outside those trials is illegal, and warns that illicit retatrutide products may contain "unknown ingredients, harmful contaminants and impurities." The results above come from a controlled trial in which participants received the study drug under medical supervision.

Sources

• Eli Lilly and Company. Lilly's retatrutide delivered greater A1C reduction and more than double the weight loss of Ozempic's highest approved dose in head-to-head trial. Press release, October 28, 2026. (TRANSCEND-T2D-2, NCT06260722)
• Lilly Medical. How did retatrutide compare with semaglutide 2 mg in adults with type 2 diabetes in TRANSCEND-T2D-2? Reviewed October 28, 2026.
• Eli Lilly and Company. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026. (TRIUMPH-2)
• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026; updated October 22, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1)
• Eli Lilly. What to know about retatrutide. Last updated September 2026.

Medical Disclaimer: This article is for informational purposes only and is not medical advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and Lilly says anything sold to consumers under its name outside its clinical trials is illegal. The figures described here are those reported in clinical trials under medical supervision.