Quick answer: in trials of retatrutide for diabetes, the phase 3 TRANSCEND-T2D-1 study lowered HbA1c by 1.69 to 1.94 percentage points over 40 weeks, versus 0.81 on placebo, and weight by 11.5% to 15.3%.[1] In adults with obesity and type 2 diabetes (TRIUMPH-2), weight fell by up to 18.8% over 80 weeks.[3] Retatrutide is investigational and not FDA-approved for diabetes or anything else.
Below are the results of each diabetes trial, the side effects, and what is still being tested. For an overview of the drug, see the retatrutide profile.
Why a triple agonist for type 2 diabetes?
Retatrutide activates three hormone receptors: GLP-1, GIP and glucagon. GLP-1 and GIP drugs boost insulin after meals and reduce appetite. Glucagon normally raises blood sugar, so adding it to a diabetes drug may sound odd. The idea is that the GLP-1 and GIP actions offset glucagon’s sugar-raising effect while glucagon adds energy use and liver fat loss. Our explainer on how retatrutide works covers this in more detail.
The type 2 diabetes trials at a glance
| Trial | Who | Weeks | Main result |
|---|---|---|---|
| Phase 2 (USA) | 281 adults with type 2 diabetes | 36 | HbA1c −2.02 points at 24 weeks on 12 mg |
| TRANSCEND-T2D-1 (phase 3) | 537 adults, diet and exercise only | 40 | HbA1c −1.69 to −1.94 points |
| TRIUMPH-2 (phase 3) | 1,152 adults with obesity and diabetes | 80 | Weight −11.9% to −18.8% |
| TRANSCEND-T2D-2 (phase 3) | about 1,250 adults on metformin, vs semaglutide | 80 | Not yet reported |
| TRANSCEND-T2D-3 (phase 3) | about 320 adults on insulin with kidney impairment | 52 | Not yet reported |
Sources: phase 2,[5] TRANSCEND-T2D-1,[1] TRIUMPH-2,[3] TRANSCEND-T2D-2,[7] TRANSCEND-T2D-3.[8][9]
TRANSCEND-T2D-1: retatrutide as a first diabetes drug
This 40-week trial enrolled 537 adults whose type 2 diabetes was not controlled by diet and exercise alone. They had had diabetes for an average of 2.5 years, with a starting HbA1c of 7.9% and an average BMI of 35.8. They took 4 mg, 9 mg or 12 mg of retatrutide, or placebo, once a week, at 48 sites in the USA, Mexico and India. Of the 537 participants, 91% finished the treatment period on the study drug.[1]
Counting everyone randomized (the treatment-regimen estimand):[1]
| Dose | HbA1c change | Weight change |
|---|---|---|
| 4 mg | −1.69 points | −11.5% |
| 9 mg | −1.86 points | −13.9% |
| 12 mg | −1.94 points | −15.3% |
| Placebo | −0.81 points | −2.6% |
Lilly’s figure for people who stayed on treatment was a 16.8% weight loss on 12 mg (36.6 lb).[2] The American Diabetes Association noted that weight loss had not leveled off by week 40.[9]
No severe hypoglycemia (low blood sugar needing help) was reported. Two people died during the trial, both on 4 mg, and investigators judged neither death related to the drug.[1]
Earlier phase 2 diabetes results
The phase 2 trial, run in 281 US adults with type 2 diabetes, compared several retatrutide doses with placebo and with dulaglutide 1.5 mg (Trulicity).[5]
- At 24 weeks, HbA1c fell 2.02 points on 12 mg, versus 1.41 on dulaglutide and 0.01 on placebo.[5]
- At 36 weeks, 80% of people on 12 mg had an HbA1c under 7%, compared with 60% on dulaglutide and 22% on placebo.[6]
- Weight fell 16.94% on 12 mg at 36 weeks, versus 2.02% on dulaglutide.[5]
- The lowest dose, 0.5 mg, did not lower HbA1c significantly more than placebo.[5]
TRIUMPH-2: obesity plus type 2 diabetes
TRIUMPH-2 was designed mainly as a weight trial. It enrolled 1,152 adults with type 2 diabetes and a BMI of 27 or more. Most (92%) were already taking oral diabetes medicines, and their average starting HbA1c was 7.71%.[3]
Over 80 weeks, counting everyone randomized, weight fell 11.9% on 4 mg, 16.8% on 9 mg and 18.8% on 12 mg, versus 5.1% on placebo.[3] Lilly reported HbA1c reductions of 1.4 to 1.6 points among people who stayed on treatment, versus 0.2 on placebo.[4]
People with diabetes usually lose less weight on these drugs than people without it. TRIUMPH-1, in adults without diabetes, reached 25.0% on 12 mg. See retatrutide weight loss results for the comparison.
Side effects in people with diabetes
Stomach and bowel effects were the most common, and they rose with dose.
- TRANSCEND-T2D-1: nausea affected 16.4% to 26.5% on retatrutide versus 3.7% on placebo, mostly during dose increases. Between 2.2% and 5.1% stopped because of side effects, versus none on placebo.[2]
- TRIUMPH-2: diarrhea affected 27% to 34% versus 13%, and nausea 14% to 28% versus 8%. Low blood pressure (1% to 6%) and dysesthesia, an abnormal skin sensation (4% to 7%), were more common than on placebo.[3]
Full numbers are in our retatrutide side effects guide.
Kidney markers in diabetes
Diabetes is a leading cause of kidney disease. In a later analysis of the phase 2 diabetes trial, 12 mg lowered urine albumin (a sign of kidney stress) by 37% versus placebo at 36 weeks, with no change in estimated kidney filtration.[11] This was an exploratory analysis in people with mostly normal kidney function. TRANSCEND-T2D-3 is testing retatrutide in people with moderate or severe kidney impairment who use basal insulin.[8]
What is still unknown
- Head-to-head data: TRANSCEND-T2D-2 is an open-label trial comparing two retatrutide doses with semaglutide in adults taking at least 1,500 mg of metformin a day, with or without an SGLT2 inhibitor. Its main measure is HbA1c at 80 weeks, with weight, cholesterol and blood pressure as secondary measures. Its primary completion date was August 2026, and results had not been released as of our review.[7]
- Insulin users: TRANSCEND-T2D-3, the insulin and kidney impairment trial, has an estimated primary completion in October 2026. It also tracks time spent in the target glucose range on continuous glucose monitors.[8]
- Long-term complications: no trial has yet shown whether retatrutide reduces diabetes complications such as heart attacks, kidney failure or eye disease.
- Approval for diabetes: Lilly said in August 2026 that its data package supports registrations for obesity, sleep apnea and knee osteoarthritis pain, with an FDA submission planned for the first quarter of 2027. Type 2 diabetes was not among the indications named.[10] See when will retatrutide be available?
Questions to ask a clinician
- Which approved diabetes medicine fits my HbA1c, weight and heart and kidney risk?
- If I take insulin or a sulfonylurea, how would a GLP-1-type drug change my low blood sugar risk?
- Am I eligible for a retatrutide diabetes trial?
For context on approved options, see our guides to peptides for diabetes and retatrutide vs semaglutide.
