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Retatrutide TRIUMPH-2: 20.8% Weight Loss in Type 2 Diabetes, Live From EASD

Lilly's triple agonist just posted its first phase 3 readout in type 2 diabetes at EASD Milan, published in The Lancet. Here is what TRIUMPH-2 actually showed.

EASD week is delivering again. Overnight (Milan time), Eli Lilly presented detailed results from TRIUMPH-2, the first phase 3 trial of retatrutide in people with type 2 diabetes and obesity or overweight. The results were published simultaneously in The Lancet, which means the full dataset is public, not just a press release.

This is the one the retatrutide community has been waiting on. TRIUMPH-1 covered obesity without diabetes back in June. TRIUMPH-2 answers the harder question: does the triple agonist still deliver in a population that historically loses less weight on these drugs?

What the Research Says

TRIUMPH-2 (NCT05929079) randomised 1,152 adults with type 2 diabetes and a BMI of 27 or higher to once-weekly retatrutide at 4 mg, 9 mg, or 12 mg, or placebo, for 80 weeks across 92 sites in eight countries. Baseline stats tell you who was in the room: mean BMI 38.2, mean HbA1c 7.71%, median duration of diabetes 5.6 years. Results per The Lancet publication (DOI: 10.1016/S0140-6736(26)01861-1) and Lilly’s announcement:

  • Weight change at 80 weeks (treatment regimen estimand): -11.9% on 4 mg, -16.8% on 9 mg, -18.8% on 12 mg, versus -5.1% on placebo. All dose comparisons hit p<0.0001. Lilly’s headline figure of 20.8% (49.6 lbs) on the 12 mg dose uses the adherence-based estimand from the same trial
  • Among participants starting at BMI 35+, the 12 mg group averaged 23.4% loss (60.8 lbs)
  • 59.5% of the 12 mg group no longer met the BMI criteria for obesity by study end
  • A1C fell up to 1.6%, and up to 40% of participants reached an A1C below 5.7% - the non-diabetic range. That is the number that made trial investigators talk about changing treatment goals, not just hitting old ones
  • Cardiovascular markers moved too: at the highest dose, triglycerides down 39.5%, systolic blood pressure down 10.8 mmHg, hsCRP down 58.3%

Safety looked like the GLP-1 class playbook: diarrhoea in 27-34% versus 13% on placebo, nausea in 14-28% versus 8%. Two signal flags worth knowing about - dysesthesia (abnormal skin sensations) ran at 4-7% versus 1% on placebo, and dose-related hypotension appeared in the 9 mg and 12 mg groups. Deaths occurred in all four arms (seven total across 1,152 participants) and investigators judged all unrelated to the drug.

The Context That Matters

Two things sit around this readout. First, type 2 diabetes populations have consistently seen smaller weight-loss numbers than non-diabetic populations across every incretin trial ever run - the -18.8% here against -28.3% in TRIUMPH-1’s obesity-only cohort follows that pattern. Whether that is biology (insulin resistance, prior medication exposure) or trial composition is still argued, but the delta is real and it is the honest number for this population.

Second, retatrutide remains investigational everywhere. Lilly has said it plans to file a Biologics License Application with the FDA in the first quarter of 2027, so no regulator has assessed it yet - approval is realistically 2027 at the earliest. Lilly has also been actively suing black market sellers of grey-market retatrutide since August (we covered the lawsuits alongside the grey market dynamics), and the TGA has previously flagged counterfeit injectable products in Australia - see our counterfeit safety warning coverage.

The Australian Angle

Nothing here changes Australian regulatory status. Retatrutide is not scheduled for a TGA decision because there is no application to assess. When Lilly files in the US, the eventual Australian pathway - if it comes - would follow, likely years behind. Until then, the only lawful source of retatrutide is a Lilly clinical trial, full stop.

What is worth tracking from Australia is the evidence pipeline: the TRIUMPH program is also running cardiovascular and renal outcomes trials, and outcome data is exactly what PBS conversations weigh. The full TRIUMPH program has enrolled over 5,800 participants with more readouts expected over the next year.

For a compound-by-compound rundown of where retatrutide sits against the approved incretins, see our retatrutide research overview and the tirzepatide page.

Sources

Disclaimer: This article is for educational and informational purposes only. It does not constitute medical advice, therapeutic recommendations, or endorsements of any compound. Grey Highway is a research-education community. We do not sell, supply, or promote the use of research compounds. Always consult a qualified healthcare professional regarding health decisions. For Australian regulatory information, visit the TGA website.