Lilly has posted full results for ACHIEVE-2, the Phase 3 trial that pitted orforglipron, its once-daily GLP-1 pill, against dapagliflozin (Farxiga) in 962 adults with type 2 diabetes already taking metformin. At the two higher doses tested, orforglipron lowered HbA1c by about a full percentage point more than dapagliflozin over 40 weeks and took off three to four kilograms more weight. These are registry results posted on ClinicalTrials.gov on 16 October 2026, not a peer-reviewed paper.
What the trial measured
Participants had an average age of 56 and a mean starting HbA1c of 8.14%, and had been on a stable metformin dose for at least 90 days. They were randomised to one of three orforglipron arms, listed in the registry as 3 mg, 12 mg and 36 mg once daily, or to dapagliflozin 10 mg, an SGLT2 inhibitor that is a common second step after metformin. The trial was open-label: everyone knew which drug they were taking.
The primary endpoint was change in HbA1c at week 40. Dapagliflozin lowered it by 0.76 points. Orforglipron lowered it by 1.32 points at 3 mg, 1.74 at 12 mg and 1.73 at 36 mg. The registry gives the gap against dapagliflozin as 0.98 points at 12 mg (95% confidence interval 0.79 to 1.17) and 0.96 at 36 mg (0.75 to 1.18). Both intervals sit well clear of zero, so the advantage is not a matter of chance. The share of people reaching an HbA1c below 7% was 80% on 12 mg and 78% on 36 mg, against 37% on dapagliflozin.
Weight fell by 7.3% on the 36 mg dose, 6.3% on 12 mg and 3.5% on 3 mg, against 3.0% on dapagliflozin. The 36 mg arm’s extra loss was 4.4 percentage points (3.3 to 5.5), or about 4.0 kg; at 12 mg it was 3.4 points, or 3.1 kg. At 3 mg the difference was 0.5 points with an interval running from 1.4 points better to 0.4 points worse, so the lowest dose did no better than dapagliflozin on weight. About one in three people on 36 mg lost at least 10% of their body weight, against roughly one in 18 on dapagliflozin.
How it fits, and the cost in side effects
ACHIEVE-2 is the third orforglipron diabetes trial this site has covered, after the comparison with oral semaglutide in ACHIEVE-3 and the heart-safety readout against insulin in ACHIEVE-4. Its comparator is the most practically useful so far, because an SGLT2 inhibitor is what many people with type 2 diabetes are offered once metformin alone stops working. Weight loss in people with diabetes typically runs lower than in obesity trials, and the 7.3% here is in line with that pattern; it should not be compared directly with obesity-trial figures.
The gastrointestinal price was clear. Nausea was recorded in 22% of the 36 mg arm (54 of 241) against under 2% on dapagliflozin (4 of 240); diarrhoea in 20% against 5%; vomiting in 12% against 2%. Six people on 36 mg and three on each lower dose left the trial because of adverse events, against none on dapagliflozin. One death was recorded, in the dapagliflozin arm. Treatment satisfaction scores did not differ between any orforglipron dose and dapagliflozin.
What is not yet known
This is a sponsor’s registry posting. It has not been through peer review, and the full methods, the handling of missing data and subgroup results are not yet public. Because the trial was open-label, self-reported outcomes such as satisfaction and quality of life may be coloured by expectation, although HbA1c and weight are objective. Forty weeks says nothing about durability or long-term safety, and dapagliflozin’s heart and kidney benefits, which are established in outcome trials, were not what this study was built to measure. The trial was funded and run by Lilly.
Sources: ClinicalTrials.gov NCT06192108, ACHIEVE-2: orforglipron compared with dapagliflozin in adults with type 2 diabetes on metformin, results first posted 16 October 2026 (sponsor: Eli Lilly and Company; not peer-reviewed).
