As blogged previously, retatrutide ( a ‘triple G’ agonist of GLP1, GIP and glucagon) has demonstrated weight loss similar to bariatric surgery in people without diabetes.

Retatrutide has now also demonstrated impressive improvement in health and weight in people with type 2 diabetes. The TRANSCEND-T2D-1 trial randomized 537 people with type 2 diabetes (on no diabetes medicine at baseline) in India, Mexico, and USA to receive retatrutide at doses of 4mg, 9mg, 12mg weekly or placebo. At the start of the study, average weight was 96.9kg, average BMI was 35.8 , average duration of diabetes was 2.5 years, and average a1c was 7.9%. This study stands apart with excellent ethnic diversity, with about a third of participants identifying as Asian, and over a third as American Indian or Alaska Native). Impressively, most people (94-99%) were able to reach their randomly assigned dose, though 9% percent of retratrutide patients and 7% of placebo patients stopped treatment during the trial (the main reason for stopping retatrutide was side effects, and the main reason for stopping placebo was participant withdrawal).

At 40 weeks, the study found with:

  • retatrutide 4mg: A1c reduction 1.69%, weight loss 11.5% (weight still going down at end of trial)
  • retatrutide 9mg: A1c reduction 1.86%, weight loss 13.9% (A1c and weight still going down at end of trial)
  • retatrutide 12mg: A1c reduction 1.94%, weight loss 15.3% (A1c and weight still going down at end of trial)
  • placebo: A1c reduction 0.81%, weight loss 2.6%

In addition, authors found that 35-40% of people treated with retatrutide achieved an A1c (diabetes report card) of less than 5.7% (a normal A1c by US criteria). Improvements in waist, cholesterol and blood pressure were also seen with retatrutide. Diarrhea was seen in 19-26% of retatrutide patients vs 4% with placebo, nausea was seen in 16-26% of retatrutide patients vs 4% with placebo; vomiting in 15-18% of retatrutide patients vs 2% with placebo. Dyesthesia (an altered or unusual skin sensation – more on this blogged here) occurred in 4% of retatrutide participants, generally mild to moderate, and the majority resolved while participants continued on treatment with retatrutide. Three people on retatrutide reported severe dysesthesia, and two of those stopped treatment because of this.

BOTTOM LINE: Retatrutide is proving to be a powerhouse in reducing weight (with or without diabetes), and improving diabetes control and weight in an ethnically diverse population. Importantly, these results have come with pretty good gastrointestinal tolerability. 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 people achieve their treatment goals, being cautious to avoid weight loss that is too much, or too fast.

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).


Share this blog post using your favorite social media link below!

Follow me on X/twitter! @drsuepedersen

www.drsue.ca © 2026