Yes, on the measure diabetes trials are built around. Across three phase 3 trials in adults with type 2 diabetes, orforglipron lowered HbA1c by 1.23 to 1.91 percentage points. It beat every comparator it faced: placebo [2], dapagliflozin [1] and oral semaglutide [3]. The price was more nausea-type side effects and more people stopping treatment. Orforglipron’s first US approval, in April 2026, was for weight management, covered in what orforglipron is.
Against placebo, in early diabetes
ACHIEVE-1 enrolled 559 adults whose diabetes was treated with diet and exercise alone, at a mean starting HbA1c of 8.0% [2]. Over 40 weeks HbA1c fell 1.24, 1.47 and 1.48 percentage points on the 3, 12 and 36 mg doses, against 0.41 on placebo. Mean HbA1c ended at 6.5% to 6.7% on the drug. Weight fell 4.5% to 7.6% against 1.7% on placebo. Adverse events ended treatment for 4.4% to 7.8% on orforglipron against 1.4% on placebo.
The phase 2 trial that set those doses ran 26 weeks in 383 adults [4]. HbA1c fell by up to 2.10% on orforglipron, against 0.43% on placebo and 1.10% on injected dulaglutide. Body weight fell by up to 10.1 kg.
Against dapagliflozin, added to metformin
ACHIEVE-2 tested it where most diabetes drugs are actually decided: as the thing added when metformin is no longer enough [1]. The design deserves a moment because the phrase appears constantly and is rarely explained. A non-inferiority trial does not set out to show a drug is better. It sets out to show the drug is not worse by more than an agreed margin, here 0.3 percentage points of HbA1c.
It did considerably more than hold its own. In 962 adults at week 40, HbA1c fell 1.23, 1.50 and 1.56 percentage points on the three doses against 0.81 with dapagliflozin. The treatment differences were −0.42 (95% CI −0.62 to −0.23), −0.70 (−0.90 to −0.49) and −0.75 (−0.96 to −0.55). A trial built to show a tie produced a win, which is a stronger signal because nobody designed it to find one.
Against the other GLP-1 tablet
ACHIEVE-3 is the comparison a tablet buyer would ask for: orforglipron against oral semaglutide, both once daily, in 1,698 adults on metformin for 52 weeks [3]. From a starting HbA1c of 8.3%, it fell 1.71 and 1.91 points on orforglipron 12 and 36 mg, against 1.23 and 1.47 on semaglutide 7 and 14 mg. Both orforglipron doses beat both semaglutide doses, including 12 mg against 14 mg, by 0.24 points (95% CI −0.41 to −0.072).
Oral semaglutide has to be taken on an empty stomach with little water, a routine set out in what the pill does. Orforglipron was designed to be taken without food or water restrictions [3].
What it costs in tolerability
Every trial reports the same trade. In ACHIEVE-2, gastrointestinal events affected 46% to 54% of the orforglipron groups against 12% on dapagliflozin. Between 15% and 20% stopped the study drug, against 6% [1]. In ACHIEVE-3, 9% and 10% stopped because of adverse events against 4% and 5% on semaglutide. Pulse rose 3.7 and 4.7 beats per minute on orforglipron against 1.0 and 1.5 [3].
One design choice makes these results more useful than they might have been. ACHIEVE-2 and ACHIEVE-3 counted each participant’s data whether or not they stopped the drug or added another. That measures what happens when someone is put on a drug, not what happens if they stay on it perfectly. Given how often people stop, that is the more honest question, and the network meta-analysis of nineteen drugs puts orforglipron among the highest for stopping because of adverse events.
Both active-comparator trials were open-label, so everyone knew what they were taking. HbA1c is a laboratory measure and difficult to influence directly, but knowing you are on the new drug can change adherence and effort. Where orforglipron sits among the other tablets in development is in the guide to GLP-1 pills, and the wider pipeline includes ecnoglutide.