A new oral diabetes medication has delivered the strongest results ever seen from a GLP-1 pill in head-to-head clinical trials, outperforming the current standard of care and achieving weight loss comparable to injectable therapies — all without the requirement to take it on an empty stomach.
The drug is orforglipron, sold under the brand name Foundayo by Eli Lilly. It belongs to the same GLP-1 receptor agonist class as semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound), but with a fundamental difference: it is a synthetic small molecule, not a peptide. This means it can be taken as a simple once-daily tablet at any time, with or without food, and is cheaper to manufacture at scale.
Three Phase 3 trials — collectively called the ACHIEVE program — were presented simultaneously at the American Diabetes Association’s 86th Scientific Sessions in Chicago (June 5-8, 2026) and published in The Lancet.
The marquee trial, ACHIEVE-3, randomized 1,698 adults with type 2 diabetes inadequately controlled on metformin to receive either orforglipron or oral semaglutide (Rybelsus) for 52 weeks across 131 sites globally.
The results: orforglipron at 36 mg reduced HbA1c by 2.2 percentage points, compared to 1.4 percentage points for oral semaglutide — a 57% greater relative reduction. Weight loss was similarly dramatic: patients on orforglipron lost 12.4% of their body weight (approximately 19.7 lbs), versus 5.3% (approximately 11.0 lbs) on oral semaglutide.
The trial was open-label, meaning participants and clinicians knew which drug was being taken — a limitation the researchers acknowledge.
ACHIEVE-2 compared orforglipron against the SGLT2 inhibitor dapagliflozin in 962 patients over 40 weeks. Orforglipron achieved HbA1c reductions of up to 1.7% versus 0.8% for dapagliflozin — roughly double the effect — and 68.6% of patients reached an HbA1c of 6.5% or below.
ACHIEVE-1, a placebo-controlled monotherapy trial in 559 patients with early type 2 diabetes, showed HbA1c reductions of up to 1.6% compared to 0.1% for placebo, with weight loss of up to 7.9% of body weight (approximately 15.8 lbs) — and weight was still trending downward at 40 weeks.
A fourth trial, ACHIEVE-5, tested orforglipron as an add-on to basal insulin in 546 patients and found HbA1c reductions of up to 2.05% versus 0.77% for placebo, all statistically significant.
Side effect profile
The gastrointestinal side effect profile is typical of the GLP-1 class. Nausea occurred in up to 36% of patients at the highest doses, with diarrhea (up to 31%), constipation (up to 30%), and vomiting (up to 28%) also common. Most events were mild to moderate, with 5.1% to 10.6% of patients discontinuing due to adverse events, depending on dose.
The drug requires gradual dose escalation to mitigate GI side effects — a familiar pattern for anyone who has used injectable GLP-1s.
Already approved for weight
Foundayo was approved by the FDA for chronic weight management in April 2026, based on the separate ATTAIN obesity trials that showed average weight loss of approximately 25 to 27 pounds. The ACHIEVE data support a supplemental NDA filing for type 2 diabetes, which Eli Lilly has said it plans to submit later this year.
Originally discovered by Chugai Pharmaceutical in Japan and licensed to Eli Lilly in 2018, orforglipron represents a new chemical class — non-peptide GLP-1 receptor agonists — that could reshape the oral diabetes drug market.
Caveats
Long-term cardiovascular outcomes data are not yet available. The SURMOUNT and SELECT trials for injectable GLP-1s have shown cardiovascular benefits, but whether orforglipron provides similar protection remains unknown. The drug also has not been tested head-to-head against tirzepatide (Mounjaro), which combines GLP-1 and GIP agonism and has set the highest bar for weight loss among approved therapies.
“These are impressive data for an oral agent,” Dr. Julio Rosenstock, lead investigator of ACHIEVE-1 and ACHIEVE-3, said at the ADA meeting. “But we need to see CVOT data and real-world experience before we fully understand where this drug fits.”
Pricing has not been announced, though the simpler manufacturing process for small molecules could eventually lead to lower costs than peptide-based GLP-1s, which currently exceed $1,000 per month.
Source: Rosenstock, J., Yabe, D., Cox, D., et al. “Orforglipron versus oral semaglutide in type 2 diabetes (ACHIEVE-3).” The Lancet (2026). DOI: pending (published online February 26, 2026). ACHIEVE-2 data presented at ADA 86th Scientific Sessions, June 2026, and published in The Lancet (DOI: S0140-6736(26)00800-7).