Eli Lilly posts Phase 3 orforglipron results against dapagliflozin
Eli Lilly posted ACHIEVE-2 results on ClinicalTrials.gov on 2026-10-16. The record reports Week 40 blood-sugar and body-weight measures in 962 adults with type 2 diabetes taking metformin.
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Eli Lilly and Company posted results from ACHIEVE-2, a Phase 3 study comparing once-daily oral orforglipron with dapagliflozin in adults with type 2 diabetes whose blood sugar remained inadequately controlled with metformin. The ClinicalTrials.gov record lists results on 2026-10-16. The randomized, open-label study enrolled 962 participants and followed treatment through Week 40.
What the record reports
The primary measure was change from baseline in HbA1c at Week 40. The record lists least-squares mean changes of -1.32 percentage points with orforglipron 3 mg, -1.74 with 12 mg and -1.73 with 36 mg. The dapagliflozin 10 mg group had a -0.76-point change. The registry also reports the prespecified noninferiority comparisons against dapagliflozin, with a 0.3% noninferiority margin. The listed differences were -0.56, -0.98 and -0.96 percentage points for the three orforglipron doses, respectively.
The record also includes superiority analyses for the same measure. It reports p-values of <.001 for each orforglipron dose compared with dapagliflozin, alongside 95% confidence intervals for the differences. The registry presents these as posted results from the registered analyses, rather than as a separate company announcement about the findings.
At Week 40, 63.25% of participants in the 3 mg group, 80.09% in the 12 mg group and 77.94% in the 36 mg group had an HbA1c value below 7.0%. The corresponding figure in the dapagliflozin group was 37.03%. For the lower target of 6.5% or less, the results were 54.62%, 66.69% and 68.62% with orforglipron, compared with 21.59% with dapagliflozin. The record says missing Week 40 data for these measures were imputed using a multiple-imputation method.
Participants and treatment
The trial enrolled adults with a clinical diagnosis of type 2 diabetes and an HbA1c between 7.0% and 10.5% at screening. Participants had been taking a stable dose of metformin of at least 1500 mg per day for 90 days before screening and through randomization. The record also required stable body weight and a body mass index of at least 23.0 kg/m². It excluded people with type 1 diabetes and those treated with antihyperglycemic medicines other than metformin in the 90 days before screening.
Participants were assigned to four groups: 240 to orforglipron 3 mg, 241 to 12 mg, 241 to 36 mg and 240 to dapagliflozin 10 mg. Each orforglipron group began at 1 mg once daily. The 3 mg dose was reached at Week 4. The 12 mg group escalated through 3 mg at Week 4 and 6 mg at Week 8, reaching 12 mg at Week 12. The 36 mg group escalated every four weeks, reaching 36 mg at Week 20. Each assigned dose continued through Week 40. Dapagliflozin was given at a fixed 10 mg dose from randomization through Week 40.
Weight and safety measures
The registry lists mean percent change in body weight at Week 40 as -3.5% with orforglipron 3 mg, -6.3% with 12 mg, -7.3% with 36 mg and -3.0% with dapagliflozin. The 95% confidence interval for the difference between the 3 mg dose and dapagliflozin ran from -1.4 to 0.4 percentage points. For the 12 mg and 36 mg doses, the reported differences were -3.4 and -4.4 percentage points, with intervals from -4.3 to -2.4 and -5.5 to -3.3, respectively.
In the safety table, the record lists serious adverse events in 8 of 240 participants receiving 3 mg, 14 of 241 receiving 12 mg, 10 of 241 receiving 36 mg and 11 of 240 receiving dapagliflozin. It lists one death in the dapagliflozin group and none in the orforglipron groups. Other adverse events were recorded for 174, 180, 180 and 154 participants in those groups, respectively. These are the counts reported in the registry for the study period.
The study record says the study began on 2024-01-10 and reached primary completion on 2025-09-26. Its listed outcomes cover blood-sugar measures, weight, blood lipids, blood pressure, fasting serum glucose, participant-reported health status and treatment satisfaction. The registry record provides the study’s posted results and descriptions of the populations and analyses for those measures.