Is retatrutide 'best ever' for weight loss in type 2 diabetes?

As blogged previously, retatrutide is a GLP1, glucagon, and GIP (‘triple G’) agonist that has demonstrated previously unsurpassed weight loss in people without type 2 diabetes, well into the range of weight loss achieved with bariatric surgery. There is lots of activity on social media platforms in the last few days touting retatrutide (aka ‘reta’) as ‘record setting’ and ‘best ever’ for weight loss in people with type 2 diabetes, based on a recent press release. Let’s do a deep dive to really understand what has been reported.

The high level press release of the TRIUMPH-2 study informs us of the effects of retatrutide in people with type 2 diabetes, with weight loss as the focus of this study. This study enrolled 1,152 people with type 2 diabets and obesity (BMI ≥27) and randomized them to receive retatrutide 4 mg, 9 mg, 12 mg weekly, or placebo. At 80 weeks, they found:

weight loss 12.7% with retatrutide 4mg
weight loss 19.1% with retatrutide 9mg
weight loss 20.8% with retatrutide 12mg
weight loss 4% with placebo

Diabetes control improved with retatrutide, with A1c (diabetes report card) reductions of 1.4-1.6% with retatrutide, vs -0.2% with placebo.

If you’re a regular reader, you might have noticed that the weight loss in this study is a little more than in the diabetes-focused retatrutide study (TRANSCEND-1-T2D – blogged here), and that A1c reduction is a little less. This may be because A1c reduction tends to be greater in diabetes-focused studies, and weight loss tends to be a little more in weight-focused studies. Importantly, while the reported weight loss results in TRIUMPH-2 are numerically greater than seen in other studies of GLP1 medicines in people with type 2 diabetes, it’s important to note that the weight loss in TRIUMPH-2 press release are reported for people taking treatment as intended (scientists: efficacy estimand). The press release does not report the more conservative (often lesser) treatment regimen estimand results, which looks at all randomized patients as a whole group over time, capturing the actual practical outcome even if someone doesn’t take the treatment as prescribed, stops the injections or drops out of the trial. We will find out those numbers when the full study results are published.

Side effects were in keeping with what is already known for retatrutide and the GLP1 class, primarily gastrointestinal (diarrhea, nausea, constipation). There was an increased risk of dysesthesia (as noted in other trials). Urinary tract infections were seen in 3.8% (4mg), 6.3% (9mg), 8.0% (12mg) vs. 6.6% with placebo. Discontinuation rates due to adverse events were fairly low at 3.8% (4 mg), 11.6% (9 mg), and 7.7% (12 mg) with retatrutide, vs 4.9% for placebo.

BOTTOM LINE: Retatrutide again proves to be a powerful medicine to improve weight and blood sugars in people with type 2 diabetes. We await the full disclosure of the TRIUMPH-2 study results before we can confidently conclude that it is ‘best ever’ for weight loss in people with diabetes. Regardless of where the exact average percent weight loss pans out, remember that at the end of the day, weight management should be more about health gains and improvement in well being and quality of life, than the numbers on the scale. If/when this medication becomes approved for use, the key will be to titrate carefully as needed, as tolerated, and as appropriate to each individual to help each person achieve their treatment goals.

Disclaimer: I am an investigator in clinical trials of retatrutide. I receive honoraria as a continuing medical education speaker and consultant from the maker of retatrutide (Eli Lilly).

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