# Does Orforglipron Work for Type 2 Diabetes? Three Phase 3 Trials | This GLP

Orforglipron cut HbA1c 1.23 to 1.91 points in three phase 3 trials | it beat placebo, dapagliflozin and oral semaglutide, with more side effects and discontinuations.

Publisher: This GLP Editorial Team
Canonical: https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes
Updated: 2026-10-26
Published: 2026-09-17

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Evidence

# Does Orforglipron Work for Type 2 Diabetes? Three Phase 3 Trials

Yes, on blood sugar. HbA1c fell 1.23 to 1.91 points and the tablet beat placebo, dapagliflozin and oral semaglutide. More people stopped it than stopped either active comparator.

[This GLP Editorial Team](https://thisglp.com/about)September 20268 min readUpdated September 2026

HbA1c fall at week 40, percentage points · orforglipron 36 mg · −1.56 · orforglipron 12 mg · −1.50 · orforglipron 3 mg · −1.23 · dapagliflozin 10 mg · −0.81 · The trial only had to prove it was no worse.

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## Key takeaways

-   Yes, on blood sugar. In three phase 3 trials, HbA1c fell 1.23 to 1.91 percentage points on orforglipron, and it beat placebo, dapagliflozin and oral semaglutide.
-   Against oral semaglutide over 52 weeks in 1,698 adults, HbA1c fell 1.71 and 1.91 points on orforglipron against 1.23 and 1.47 on semaglutide.
-   Against dapagliflozin over 40 weeks in 962 adults, a trial built only to show a tie, all three doses won outright.
-   The cost is tolerability: more gastrointestinal events and more people stopping than on either active comparator.
-   No severe hypoglycemia was reported in the placebo-controlled or dapagliflozin trials.

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 [\[2\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-2), dapagliflozin [\[1\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-1) and oral semaglutide [\[3\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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](https://thisglp.com/research/what-is-orforglipron).

## 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% [\[2\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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 [\[4\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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 [\[1\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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.

Beating a drug on blood sugar is not beating it overall

Dapagliflozin is an SGLT2 inhibitor, and its value is not confined to glucose. That class reduces heart failure hospitalization and slows kidney disease progression, benefits an HbA1c endpoint cannot see. On at least one outcome the same class outperforms GLP-1 drugs, as [the atrial fibrillation comparison](https://thisglp.com/research/atrial-fibrillation-the-other-drug-won) shows. ACHIEVE-2 answers a narrow question well.

## 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 [\[3\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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](https://thisglp.com/research/oral-semaglutide-what-the-pill-does). Orforglipron was designed to be taken without food or water restrictions [\[3\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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% [\[1\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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 [\[3\]](https://thisglp.com/research/does-orforglipron-work-for-type-2-diabetes#ref-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](https://thisglp.com/research/the-best-losers-are-the-worst-tolerated) 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](https://thisglp.com/research/does-the-glp1-pill-work-as-well-as-the-injection), and the wider pipeline includes [ecnoglutide](https://thisglp.com/research/what-is-ecnoglutide).

## Frequently asked

Does orforglipron lower A1c?

Yes. In three phase 3 trials HbA1c fell 1.23 to 1.91 percentage points on orforglipron, depending on dose, comparator and trial length. It was superior to placebo, dapagliflozin and oral semaglutide.

Is orforglipron better than oral semaglutide for diabetes?

On HbA1c, yes, in one 52-week trial of 1,698 adults: 1.71 and 1.91 points on orforglipron against 1.23 and 1.47 on oral semaglutide. More people stopped orforglipron because of side effects, 9% to 10% against 4% to 5%.

What is a non-inferiority trial?

One designed to show a drug is not worse than a comparator by more than an agreed margin, here 0.3 percentage points of HbA1c. Orforglipron cleared that margin in two trials and then showed it was better outright.

Does beating dapagliflozin make it the better drug?

Not necessarily. Dapagliflozin belongs to a class with benefits for heart failure and kidney disease that an HbA1c endpoint does not measure, so that trial answers a narrow question.

## Sources

1.  \[1\] Welch M, Forst T, Jia W, Del Pino PO, et al. (2026). Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial The Lancet. [PMID 42259339](https://pubmed.ncbi.nlm.nih.gov/42259339/)
2.  \[2\] Rosenstock J, Hsia S, Nevarez Ruiz L, Eyde S, et al. (2025). Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes The New England Journal of Medicine. [PMID 40544435](https://pubmed.ncbi.nlm.nih.gov/40544435/)
3.  \[3\] Rosenstock J, Yabe D, Cox D, Li J, et al. (2026). Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial The Lancet. [PMID 41765029](https://pubmed.ncbi.nlm.nih.gov/41765029/)
4.  \[4\] Frias JP, Hsia S, Eyde S, Liu R, et al. (2023). Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study The Lancet. [PMID 37369232](https://pubmed.ncbi.nlm.nih.gov/37369232/)

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