On March 19, 2026, Eli Lilly announced topline results from TRANSCEND-T2D-1 — a Phase 3 trial studying retatrutide as monotherapy in approximately 480 adults with type 2 diabetes.[1] The results showed significant reductions in both blood sugar and body weight, adding a second Phase 3 dataset to retatrutide's growing evidence base and strengthening its profile as a potential next-generation treatment for metabolic disease.
This is a separate clinical program from the TRIUMPH trials that produced retatrutide's first Phase 3 readout in December 2025.[3] While TRIUMPH focused on obesity with co-morbidities (knee osteoarthritis, sleep apnea), TRANSCEND-T2D-1 evaluates retatrutide specifically as a diabetes drug — a critical distinction for its eventual regulatory path.
- A1C reductions: 1.7% (4 mg) to 2.0% (9 mg) vs. 0.8% placebo at 40 weeks
- Weight loss: up to 16.8% (12 mg) vs. 2.5% placebo — had not yet plateaued
- Dysesthesia: 2.3-4.5% across doses — dramatically lower than TRIUMPH-4's 20.9%
- Efficacy: described by analysts as comparable to Mounjaro (tirzepatide)
- Status: still not FDA-approved; no NDA submitted
Quick facts
- Trial name
- TRANSCEND-T2D-1
- Participants
- ~480
- Duration
- 40 weeks
- Doses tested
- 4 mg, 9 mg, 12 mg (weekly)
- Design
- Phase 3, double-blind, placebo-controlled
- Population
- Adults with T2D, monotherapy
- Baseline A1C
- 7.9%
What the trial showed
Blood sugar control
Retatrutide reduced A1C across all dose groups compared to placebo at 40 weeks:[1]
- 4 mg: A1C reduction of 1.7% vs. 0.8% placebo
- 9 mg: A1C reduction of 2.0%
- 12 mg: A1C reduction of 1.9%
The baseline A1C was 7.9%, meaning many participants reached near-normal blood sugar levels. These results build on Phase 2 data that showed HbA1c below 6.5% in up to 82% of participants at higher doses.[2]
Notably, the 9 mg dose produced the strongest A1C reduction (2.0%), slightly exceeding the 12 mg dose (1.9%) — suggesting that for glycemic control specifically, more drug does not always mean better results.
Weight loss
Weight reductions were dose-dependent and substantial for a diabetes trial:[1]
- 4 mg: weight loss details pending full data release
- 9 mg: significant weight reduction (exact percentage pending)
- 12 mg: 16.8% weight loss vs. 2.5% placebo
Kenneth Custer, president of Lilly's cardiometabolic health division, noted that weight loss had not yet plateaued at the end of the 40-week study — suggesting that longer treatment could produce even greater reductions.
For context, 16.8% weight loss in a T2D population at 40 weeks is notable because people with diabetes typically lose less weight on GLP-1-class drugs than people without diabetes. The Phase 2 obesity trial (in people without diabetes) showed 24.2% at 48 weeks, and TRIUMPH-4 showed 28.7% at 68 weeks.[4][3]
Metabolic improvements
Beyond A1C and weight, retatrutide improved several cardiovascular risk markers:
- Non-HDL cholesterol reduced
- Triglycerides reduced
- High-sensitivity C-reactive protein (hsCRP) reduced
- At the highest dose, systolic blood pressure decreased by 14.0 mmHg
These additional metabolic benefits are consistent with the triple-agonist mechanism — particularly the glucagon receptor component, which drives hepatic lipid metabolism.
Safety: the dysesthesia question
The most closely watched aspect of this trial was safety — specifically, whether the alarming dysesthesia rates from TRIUMPH-4 would repeat.
They did not.
In TRIUMPH-4, dysesthesia — an abnormal sense of touch — was reported in 8.8% of the 9 mg group and 20.9% of the 12 mg group. That signal raised legitimate concern about retatrutide's tolerability at therapeutic doses.[3]
In TRANSCEND-T2D-1, dysesthesia rates were dramatically lower:[1]
- 4 mg: 4.5%
- 9 mg: 2.3%
- 12 mg: 4.4%
Why the discrepancy? The large difference between TRIUMPH-4 (20.9% at 12 mg) and TRANSCEND-T2D-1 (4.4% at 12 mg) is not yet explained. Possible factors include different dose-escalation schedules, shorter treatment duration (40 vs. 68 weeks), different patient populations (T2D vs. obesity with knee OA), or statistical variation. This is reassuring but does not eliminate the concern — more data from the remaining TRIUMPH and TRANSCEND trials will be needed to understand the true incidence.
GI side effects
The gastrointestinal side-effect profile was consistent with the GLP-1 drug class, and somewhat milder than Phase 2 rates:
- Nausea: 26.5% at highest dose
- Diarrhea: 22.8%
- Vomiting: 17.6%
These are lower than the Phase 2 rates (nausea 38-43%, diarrhea 33-35%, vomiting 20-21%), which may reflect an optimized dose-escalation schedule in Phase 3.
How it compares to Mounjaro
The most immediate comparison for TRANSCEND-T2D-1 is Lilly's own tirzepatide (Mounjaro/Zepbound), which is already FDA-approved for diabetes and obesity.
Analyst reactions were mixed but largely positive:
BMO Capital Markets described the results as "meaningfully better than previous tirzepatide data," positioning retatrutide as a potentially differentiated option for patients who need maximal weight loss alongside diabetes control.
RBC Capital Markets offered a more nuanced view: "Overall tolerability and A1C reductions were worse compared to Mounjaro," but noted that "weight-reduction and discontinuation rates favored reta."
The emerging picture is that retatrutide may trade slightly less glycemic precision for substantially more weight loss — a tradeoff that could matter significantly for the large population of people with T2D who are also obese.
Cross-trial comparison caveat: No head-to-head trial between retatrutide and tirzepatide exists. All comparisons are across different trials with different patient populations, protocols, and durations. These comparisons are suggestive, not definitive.
TRANSCEND vs. TRIUMPH: two programs, one drug
Retatrutide is being developed through two separate Phase 3 programs:
TRIUMPH program (4 trials, 5,800+ participants): Evaluates retatrutide for obesity-related indications — general obesity, T2D with obesity, obstructive sleep apnea, and knee osteoarthritis. TRIUMPH-4 reported in December 2025.
TRANSCEND program: Evaluates retatrutide specifically for type 2 diabetes. TRANSCEND-T2D-1 is the first readout. Additional TRANSCEND trials are expected.
This dual-track approach positions Lilly to seek FDA approval for retatrutide across both obesity and diabetes indications — similar to the path tirzepatide took (approved as Mounjaro for diabetes in 2022, then as Zepbound for obesity in 2023).
What this means for you
Retatrutide remains not FDA-approved and is not available at pharmacies, through prescriptions, or from compounding facilities. This trial result does not change that.
What it does change is the strength of the evidence base. Retatrutide now has two Phase 3 datasets — one for obesity/OA and one for T2D — both showing substantial efficacy. The dysesthesia concern from TRIUMPH-4 looks less alarming in light of TRANSCEND-T2D-1's lower rates, though it has not been resolved.
The remaining TRIUMPH and TRANSCEND trials are expected to read out through 2026. An NDA submission could follow in late 2026 or 2027, with earliest possible FDA approval in late 2027-2028. We will cover each readout as it arrives.
For the full evidence profile — including mechanism, all clinical trials, safety data, and comparisons — see our retatrutide profile.
References
- [1]Eli Lilly and Company. “Lilly's retatrutide demonstrated significant improvements in blood sugar and weight loss in adults with type 2 diabetes in Phase 3 TRANSCEND-T2D-1 trial.” 2026. LinkRCT
Topline press release for TRANSCEND-T2D-1. n≈480. Monotherapy vs. placebo. A1C reduction up to 2.0%. Weight loss up to 16.8% at 40 weeks. Peer-reviewed publication pending.
- [2]Rosenstock J, Frias JP, Rodbard HW, et al.. “Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial.” Lancet. 2023. 402(10401):529-544 DOI PubMedRCT
Phase 2 RCT in T2D. n=281. HbA1c <6.5% in up to 82%. Active comparator (dulaglutide 1.5 mg).
- [3]Eli Lilly and Company. “Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial.” 2025. LinkRCT
Topline press release for TRIUMPH-4. n=445. 28.7% weight loss at 12 mg (68 weeks). Dysesthesia signal at 20.9% (12 mg).
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Disclaimer
This article is for educational purposes only. Retatrutide is an investigational drug that is not FDA-approved and is not available by prescription. The trial results described are topline data from a press release, not a peer-reviewed publication. This is not medical advice or an endorsement of retatrutide use. Always consult a licensed healthcare provider before making decisions about any medication or clinical trial participation.