Lilly's oral GLP-1 orforglipron tops two comparators in Phase 3 diabetes trials
Two more Phase 3 results move Lilly's orforglipron closer to becoming an oral option for type 2 diabetes, though the pill is approved in the US only for weight loss so far.
Eli Lilly's experimental oral GLP-1 pill orforglipron lowered blood sugar more than two comparison treatments in two Phase 3 trials in adults with type 2 diabetes. The drug, which carries the brand name Foundayo, met the primary endpoint in both ACHIEVE-2 and ACHIEVE-5 [1].
In ACHIEVE-2, orforglipron lowered A1C — a blood test reflecting average blood sugar over roughly three months — by up to 1.7 percentage points, compared with 0.8 points for dapagliflozin [1]. In ACHIEVE-5, orforglipron lowered A1C by an additional 2.1 points when taken with insulin glargine [1].
Details such as how many people enrolled in ACHIEVE-2 and ACHIEVE-5, how long the trials ran, and how many participants stopped treatment have not been reported [1].
The two readouts add to a run of Phase 3 results from the ACHIEVE program, which Lilly designed to test orforglipron in type 2 diabetes [1]. In ACHIEVE-1, orforglipron lowered A1C by 1.3% to 1.6% from a baseline of 8.0% at 40 weeks, and more than 65% of participants taking the highest dose reached an A1C of 6.5% or lower; participants at the highest dose lost an average of 16.0 pounds (7.9%) [1]. In ACHIEVE-3, orforglipron 36 mg lowered A1C by 2.2% versus 1.4% for oral semaglutide 14 mg, and participants lost 19.7 pounds (9.2%) versus 11.0 pounds (5.3%) [1]. In ACHIEVE-4, orforglipron met the primary objective of non-inferiority against insulin glargine, with a 16% lower risk of MACE-4 events and a 23% lower risk of MACE-3 events; in a pre-planned analysis, the risk of all-cause death was 57% lower for orforglipron than for insulin glargine [1].
Orforglipron is a small-molecule, non-peptide GLP-1 receptor agonist that binds and activates GLP-1 receptors in brain regions that regulate appetite and calorie intake [1].
Why it matters for patients
Orforglipron is a once-daily tablet that can be taken with or without food, which sets it apart from injectable GLP-1 medicines [1]. That matters for people with type 2 diabetes who would rather take a pill than give themselves a shot — but the pill's approved use is narrower than the trial results suggest. The FDA approved Foundayo on April 1, 2026, for adults with obesity, or with overweight plus at least one weight-related condition, based on the ATTAIN trial program [1]. An approval for type 2 diabetes has not been granted, and the ACHIEVE results reported so far are trial findings, not an approved diabetes indication [1].
Safety information is already on the label for the approved weight-loss use. Foundayo carries a boxed warning for the risk of thyroid C-cell tumors, and its warnings include acute pancreatitis, severe gastrointestinal reactions, acute kidney injury from volume depletion, hypoglycemia, serious allergic reactions, diabetic retinopathy complications in people with type 2 diabetes, gallbladder disease, and pulmonary aspiration during general anesthesia or deep sedation. Common side effects reported in at least 5% of patients include nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, abdominal bloating, fatigue, belching, acid reflux, gas and hair loss [1].
Pricing and insurance coverage have not been reported [1].
What happens next
Lilly has not said when or whether it will seek FDA approval of orforglipron specifically for type 2 diabetes [1]. Orforglipron is also being studied for obstructive sleep apnea and for hypertension in adults with obesity [1]. Additional ACHIEVE and ATTAIN analyses have continued to be released through mid-2026 [1].
Sources
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