Lilly's ATTAIN-1 post hoc analysis projects Foundayo cuts predicted 10-year diabetes and cardiovascular risk

Eli Lilly announced on October 1, 2026 that post hoc analyses of its ATTAIN-1 obesity trial found Foundayo (orforglipron), a once-daily oral GLP-1 pill, was associated with significant reductions in predicted 10-year risk of type 2 diabetes and cardiovascular disease in adults with obesity or overweight plus a weight-related medical problem ^[1]. The findings were published in the journal Diabetes, Obesity and Metabolism ^[1].

These are risk-model projections built from trial measurements such as weight, blood sugar, blood pressure and cholesterol — not counts of people who actually developed diabetes or had heart attacks during the study.

What the numbers show

At 72 weeks, participants taking Foundayo 5.5 mg, 9 mg and 17.2 mg showed estimated reductions of 45.0%, 50.0% and 57.0%, respectively, in predicted type 2 diabetes risk versus placebo ^[1]. The corresponding hazard ratios were 0.55 (95% CI 0.52, 0.60), 0.50 (95% CI 0.47, 0.54) and 0.43 (95% CI 0.40, 0.47) ^[1].

The absolute changes are smaller than the percentages suggest. Predicted 10-year diabetes risk at baseline was about 16.4%, 16.0% and 17.1% in the three Foundayo groups and 17.3% in the placebo group ^[1]. By 72 weeks, that predicted risk fell by 8.0, 8.8 and 9.8 percentage points in the Foundayo arms, compared with a 1.7 percentage point drop with placebo ^[1].

For heart disease, the estimated reductions versus placebo were 13% at 5.5 mg, 15% at 9 mg and 18% at 17.2 mg ^[1]. Predicted 10-year cardiovascular risk started near 8.5% to 8.9% across groups and fell by 0.6, 0.7 and 1.0 percentage points in the Foundayo arms, while rising 0.6 percentage points in the placebo group ^[1].

Two different risk calculators were used: the Cardiometabolic Disease Staging (CMDS) risk engine for diabetes and the BMI-based Framingham risk engine for cardiovascular disease ^[1]. Risk reductions versus placebo were approximated from model-based hazard ratios, with placebo as the reference group ^[1].

About the trial

ATTAIN-1 (NCT05869903) was a Phase 3, 72-week, randomized, double-blind, placebo-controlled trial of Foundayo 5.5 mg, 9 mg and 17.2 mg as monotherapy against placebo ^[1]. It enrolled 3,127 adults with obesity, or overweight with at least one of hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease, and who did not have diabetes ^[1]. Sites spanned the U.S., Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain and Taiwan, with randomization in a 3:3:3:4 ratio ^[1]. Participants started at 0.8 mg daily and stepped up every four weeks to their assigned maintenance dose ^[1].

The trial's main goal was weight loss, not disease prevention ^[1]. Lilly describes these diabetes and cardiovascular findings as post hoc analyses — meaning the questions were asked after the data were collected ^[1].

Lilly framed the results partly in economic terms. "We've also seen evidence that treating obesity and reducing the risk of its downstream consequences, like cardiovascular disease and type 2 diabetes, can meaningfully lower healthcare costs," said Thomas Seck, M.D., senior vice president of product development, Lilly Cardiometabolic Health ^[1].

Why it matters for patients

Foundayo is already FDA-approved for adults with obesity, or some adults with overweight who also have weight-related medical problems, to reduce excess body weight and keep it off alongside a reduced-calorie diet and increased physical activity ^[1]. It is a once-daily small molecule (non-peptide) oral GLP-1 receptor agonist that can be taken any time of day without restrictions on food and water ^[1].

For people weighing the pill, the practical point is what this evidence is and is not. A 57% reduction in predicted diabetes risk is a statistical projection from a calculator, not a tally of diabetes cases prevented. Whether those projections translate into fewer real heart attacks, strokes or diabetes diagnoses has not been demonstrated in these analyses, and no cardiovascular outcomes trial results for orforglipron are reported here.

Safety considerations are unchanged by this modeling. Foundayo carries a warning that it may cause thyroid tumors, including thyroid cancer, and it should not be used by people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2 ^[1]. Other serious risks include pancreatitis, severe stomach problems, dehydration leading to kidney problems, low blood sugar, serious allergic reactions, gallbladder problems and vision changes in people with type 2 diabetes ^[1]. The most common side effects include nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, fatigue and hair loss ^[1]. Oral birth control pills may not work as well while taking Foundayo ^[1].

Orforglipron is also being studied for type 2 diabetes, obstructive sleep apnea, osteoarthritis knee pain, hypertension, peripheral artery disease and stress urinary incontinence ^[2]. Timelines for those readouts have not been disclosed.