By Dr. Asnat Raziel, specialist in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal
Retatrutide and diabetes: what the TRIUMPH-2 trial showed
Retatrutide and diabetes are the focus of a new phase 3 trial called TRIUMPH-2. Eli Lilly’s investigational drug retatrutide achieved an average weight loss of 20.8% at the 12 mg dose. The company reported this in a release dated September 29, 2026. The figure refers to 80 weeks of treatment in people with obesity or overweight and type 2 diabetes.
In contrast, the paper published in The Lancet reports a weight loss of 18.8% in its primary analysis. Both numbers are correct in context, but they answer different questions. Below I explain the difference, and also what the trial does not yet tell us.
One molecule, three receptors
Retatrutide is given as a weekly injection and activates three hormone receptors: GLP-1, GIP and glucagon. This combination underlies its effect on both weight and blood sugar. You will find a detailed explanation in my guide to how the drug works.
However, retatrutide is not yet approved for use. Lilly plans to submit an application to the FDA, the US Food and Drug Administration, in the first quarter of 2027. Submitting an application does not guarantee approval, nor a date of availability in Israel.
What did the TRIUMPH-2 trial test?
TRIUMPH-2 was a randomized, double-blind, placebo-controlled trial funded by Lilly. It enrolled 1,152 adults with type 2 diabetes and a BMI of 27 or higher. BMI, the body mass index, is the ratio of weight to height. Their average age was 55, average BMI was 38.2, and average HbA1c was 7.71%. HbA1c reflects average blood sugar over the past three months.
The researchers divided participants into four groups: retatrutide 4, 9 or 12 mg, or placebo. Most of them, 92%, were already taking pills to control blood sugar. In addition, all of them had at least one unsuccessful attempt to lose weight by dieting.
Why are both 20.8% and 18.8% reported?
The company release uses the efficacy estimand. That is, it estimates what would have happened if all participants had stayed on treatment. On the other hand, the paper’s primary analysis uses the treatment-regimen estimand. This estimate also includes the effect of treatment discontinuation and other prespecified events.
- 4 mg: a 12.7% drop according to Lilly, and 11.9% in the primary analysis.
- 9 mg: a 19.1% drop according to Lilly, and 16.8% in the primary analysis.
- 12 mg: a 20.8% drop according to Lilly, and 18.8% in the primary analysis.
- Placebo: a 4.0% drop according to Lilly, and 5.1% in the primary analysis.
According to Lilly, in the 12 mg group 67.0% of participants lost at least 15% of their weight, compared with 6.4% on placebo. Moreover, 59.5% of participants in this group no longer met the BMI definition of obesity.
So when data are presented to the public, it is important to say what each number represents. The gap is not a contradiction. It shows how staying on treatment and the method of analysis shape the estimated benefit.
Retatrutide and diabetes: better blood sugar control
By the efficacy estimand, HbA1c fell by 1.4, 1.6 and 1.5 percentage points at 4, 9 and 12 mg. In contrast, on placebo it fell by only 0.2. At 9 mg, 40% of participants reached an HbA1c below 5.7%, which is the normal range. Moreover, about 79% at 9 and 12 mg reached an HbA1c of 6.5% or lower.
However, a normal value during treatment does not mean the diabetes is cured. Remission requires a different assessment, not just a measurement taken on active treatment. You can read about today’s options in my guide to obesity and type 2 diabetes.
Heart risk factors
At the high dose, Lilly also reported improvements in heart risk factors. Triglycerides fell by 39.5%, and systolic blood pressure fell by 10.8 mmHg. In addition, waist circumference fell by 16.9 cm. However, these are only markers. The trial did not test whether the drug reduces heart attacks or strokes.
Side effects are part of the picture
The paper reported mainly diarrhea and nausea. Diarrhea occurred in 27% to 34% of the retatrutide groups, compared with 13% on placebo. Nausea occurred in 14% to 28%, compared with 8% on placebo. In addition, the researchers saw more episodes of low blood pressure and of abnormal skin sensations. Permanent discontinuation due to side effects or death occurred in about 4%, 12% and 8% at increasing doses, compared with about 5% on placebo. According to the researchers, the deaths were not related to treatment.
These data highlight that judging a treatment must also include the ability to stay on it, not just the weight lost.
Retatrutide and diabetes in the wider TRIUMPH program
TRIUMPH-2 does not stand alone. The TRIUMPH-1 trial, published the same day, studied people with obesity without diabetes. There, weight loss reached 17.6%, 23.7% and 25.0% at increasing doses, compared with 3.9% on placebo. In people with diabetes, weight loss is somewhat smaller, as with other drugs in this family. However, we cannot compare different trials directly.
In addition, an editorial in The Lancet by Prof. Jens Holst discussed what we have learned from TRIUMPH-2. A newer head-to-head trial in diabetes, comparing retatrutide vs Ozempic, has since reported its first results.
A warning: retatrutide sold online
Although the drug is not approved, online sellers offer products presented as retatrutide. According to an October 2026 report, Lilly stresses that it may not be sold or marketed for human use. No regulator checks such products, and there is no certainty about their content or purity.
The bottom line on retatrutide and diabetes
The trial on retatrutide and diabetes supports its potential to treat obesity and diabetes together. However, the comparison was against placebo. So it does not prove superiority over tirzepatide, known as Mounjaro, or over semaglutide, known as Wegovy. In addition, it cannot show that the drug reduces heart attacks, extends life or maintains weight loss after stopping. Ultimately, the full body of evidence, long-term safety, tolerability and regulatory approval will decide its place in treatment.
This article provides general information and is not a substitute for personal medical advice.
References
Retatrutide in adults with obesity and type 2 diabetes: what have we learned from TRIUMPH-2?
Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity
Retatrutide Delivers 20.8% Weight Loss in Adults With Type 2 Diabetes
Eli Lilly funded the trials.
