In December 2025, Eli Lilly gave us a tease of topline data from Triumph-4, the first phase 3 trial of retatrutide to be completed. That trial looked at obesity and knee osteoarthritis over 68 weeks, and the results were rather incredible, nearly 29% weight loss for the top dose and 1 in 8 patients had no knee pain at the end of the trial. Today, we finally have our first data for diabetics.
The trial in question is called TRANSCEND-DM2-1 which is not at all confusing when you consider we abbreviate diabetes as either DM2 or DM1.
Anyways, this trial had a somewhat unique design. Inclusion criteria included type 2 diabetics with an A1c between 7 and 9.5% that had been off all treatment for diabetes for the last 90 days and had never been on insulin before. This was actually the same trial design used for the first tirzepatide diabetes trial.
There was also no weight requirement, as long as your BMI was above 23 you could enroll. The intended goal here was to see what retatrutide alone would do with no other medications compared to diet and exercise. There were 3 doses tested, 4mg, 9mg, and 12mg and of course the placebo group with 537 patients enrolled. The timeframe was short, only 40 weeks because the goal was to look at A1c change and not weight loss.
And yet.
The weight loss has basically stolen the show here. Graphic below courtesy of Lilly:
16.8% weight loss at the highest 12mg dose reproduces the phase 2 data almost exactly (that trial was 36 weeks but had faster dose escalation and more side effects) and firmly cements retatrutide as the weight loss king for diabetes right now.
There was no plateau at 40 weeks, and Lilly will report data on Triumph-2 in June 2026 which is an 80-week trial in obese diabetics. Given the amount of loss at week 40 with today’s results, I can fairly confidently say at 80 weeks we should see 23-25% weight loss with the two highest doses.
For further context, the 9mg dose essentially matched Tirzepatide and CagriSema 72-week weight loss but at only 40 weeks!
The 4mg dose at 11.5% weight loss in 40 weeks matches the lower doses of tirzepatide at 40 weeks and easily goes beyond what 2.4mg semaglutide can do in 68 weeks.
We’ll circle back to weight in a minute, the other endpoint disclosed today was A1c reduction.
Again, keep in mind, the criteria for this trial did NOT allow for any other medications for diabetes, in fact patients had to be off all anti-diabetic agents for at least 90 days. Graph again from Lilly:
Again, these are fantastic results in just 40 weeks with no other drug to help. Baseline A1c was actually low at 7.9% for a diabetes trial and retatrutide alone put the average patient in this trial back to a baseline A1c around 6%, which is firmly in the prediabetes range. These are also essentially a mirror image of the phase 2 data, except that trial allowed metformin. These also mirror what is seen with tirzepatide alone, usually 1.9-2.1% A1c reduction with the addition of other anti-diabetic medications pushing the efficacy to 2.3-2.5% in other tirzepatide trials. I suspect with retatrutide you’ll see similar results when other agents are added in, especially metformin or SGLT2i medications that can work to help lower glucose and weight even further.
What about side effects and discontinuation rates? Paragraph from Lilly:
This is basically in the middle between tirzepatide and semaglutide for side effect profile. Tirzepatide has been the gold standard in terms of side effects for diabetes now for years. Retatrutide essentially matches the nausea rate of tirzepatide but has more diarrhea and vomiting, but this is very trial dependent. Regardless, discontinuation rates were low across the board which is really the important thing.
Circling back to the weight loss to finish this out, I can’t explain just how remarkable these results are. Ozempic was approved in December 2017 for Type 2 diabetes and people were going nuts back then because it showed 5-7% weight loss in diabetics over 56 weeks in the Sustain 2 trial. Less than a decade later we’re looking at over double the weight loss in a trial that’s 4 months shorter! And the potential for more than triple that original semaglutide weight loss when extended out to 80 weeks.
For the first time this can be seen as a glimmer of hope for obese diabetic patients who oftentimes are told their only option is bariatric surgery if they have significant amounts of weight to lose. As great as Tirzepatide is, it can’t claim that in diabetic patients. This is truly astonishing.
Full trial results will be released in June 2026 at the American Diabetes Association conference, I’ll be there to be able to give even more thoughts on retatrutide, we should also have the 80-week Triumph-2 diabetes trial data by then as well. Stay tuned, things will only get more exciting from here.
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