Orforglipron dosage and evidence

What is Orforglipron?

How does Orforglipron work?

It switches on the GLP-1 receptor, like the shots do, but it works as a pill. That cuts appetite and helps the body release insulin when blood sugar is high.

What have studies in people found about Orforglipron?

Orforglipron is by far the most tested compound in this group. Seven large final-stage studies fed 11,220 people into one combined safety check. Some of those studies tested it head to head against two rival diabetes pills, oral semaglutide and dapagliflozin. It was approved in the US in April 2026. A study of whether it prevents heart attacks and strokes is under way and has reported nothing yet.

• Obesity, ATTAIN-1, 2025, 3,127 adults: after 72 weeks, people on the top dose (36 mg) lost 11.2 percent of their body weight, against 2.1 percent on a dummy pill. 36 percent lost 15 percent or more.
• Liver safety, seven large studies combined, 2026, 11,220 people: 6,920 took orforglipron and 4,300 took something else (a dummy pill, oral semaglutide, dapagliflozin or insulin glargine), for up to 104 weeks counting follow-up. Liver enzymes went down on average. Six people on orforglipron and six on the other drugs (0.1 percent each) hit the warning level for liver injury. Every orforglipron case had another cause, and none met the standard doctors use for serious drug-caused liver damage.
• Type 2 diabetes, head to head with oral semaglutide, ACHIEVE-3, 2026, 1,698 adults on metformin in five countries, 52 weeks: HbA1c is a three-month blood sugar score, and it started at 8.3 percent on average. It fell 1.71 points on orforglipron 12 mg and 1.91 on 36 mg, against 1.23 on semaglutide 7 mg and 1.47 on 14 mg. Orforglipron won on blood sugar at both dose pairings. It lost on side effects. Stomach and gut problems hit 58 to 59 percent, against 37 to 45 percent. 9 to 10 percent quit over side effects, against 4 to 5 percent. Resting pulse rose 3.7 and 4.7 beats a minute, against 1.0 and 1.5. Four people died, two on each drug. Everyone knew which drug they took. Eli Lilly paid for it.
• Obesity with type 2 diabetes, ATTAIN-2, 2026, 1,613 adults at 136 sites in ten countries, 72 weeks: they took 6, 12 or 36 mg, or a dummy pill, and 89.5 percent finished. Weight fell 5.1, 7.0 and 9.6 percent by dose, against 2.5 percent on the dummy. 6.1 to 9.9 percent quit over side effects, against 4.1 percent on the dummy. Ten people died, six on the drug and four on the dummy. Doctors judged all but two unrelated to the pills. For those two, one on the dummy and one on 12 mg, no link to the pills was reported. Eli Lilly paid for it, and several authors are staff who own company stock.
• Type 2 diabetes, against dapagliflozin, ACHIEVE-2, 2026, 962 adults on metformin, 40 weeks: HbA1c fell 1.23, 1.50 and 1.56 points on 3, 12 and 36 mg, against 0.81 on dapagliflozin 10 mg. Orforglipron won on blood sugar at every dose. It lost on side effects: stomach and gut problems in 46 to 54 percent against 12 percent, and 15 to 20 percent stopped the pills against 6 percent. Nobody had a severe blood sugar low. People knew which drug they took, though not which orforglipron dose. Eli Lilly paid for it.
• Keeping weight off after shots, ATTAIN-MAINTAIN, 2026, 376 people who had lost weight on tirzepatide (205) or semaglutide (171) shots: they switched to orforglipron or a dummy pill for 52 weeks. Among those whose weight had levelled off, the tirzepatide group kept 74.7 percent of their loss on orforglipron, against 49.2 percent on the dummy. The semaglutide group kept 79.3 percent, against 37.6 percent. The authors name the gaps themselves: nobody stayed on their shots for comparison, and it ran only one year.
• Early type 2 diabetes, ACHIEVE-1, 2025: HbA1c fell 1.24 to 1.48 points at 40 weeks, against 0.41 on a dummy pill.
• Obesity, an early study, 2023: weight fell 9.4 to 14.7 percent at 36 weeks across doses, against 2.3 percent on a dummy pill. Stomach and gut side effects were mostly mild to moderate.
• Heart attacks and strokes, ATTAIN-Outcomes (NCT07241390): a study against a dummy pill in people with heart disease or kidney disease began in December 2025. It plans about 7,140 people and expects its main result in August 2031. There is no result yet.

What this does not tell you: Eli Lilly paid for every study above, and company staff are authors on all of them. Three of the most convincing comparisons, ACHIEVE-2, ACHIEVE-3 and a long-term Japanese safety study, let people know which drug they were on. That matters most for the very things that split the drugs: stomach symptoms people report themselves, and the choice to stop. The longest anyone took it in these studies was 104 weeks, counting safety follow-up, so nothing covers years of use. No study has measured heart or kidney outcomes yet. That study is running and will not report before 2031. The weight-keeping study had no group that stayed on the shots. So it shows orforglipron beats a dummy pill at holding weight, not that it matches the shot a person came off. And no study compares orforglipron with semaglutide or tirzepatide shots, which are what it is most often weighed against.

The state of the research

The evidence, in charts

The studies we cite

• Study in people2023
  Daily oral GLP-1 receptor agonist orforglipron for adults with obesity

  A weight loss drug you swallow instead of inject, and in its first real test it worked. Adults took orforglipron tablets or a dummy tablet for about nine months. Depending on the dose, they lost between 9.4 and 14.7 percent of their body weight. The dummy group lost 2.3 percent. Stomach and bowel upset was common and mostly mild to moderate. This was a middle stage trial, built to find a dose rather than to settle the question.

  Phase 2: 9.4% to 14.7% weight loss at 36 weeks across doses versus 2.3% with placebo; GI events mostly mild to moderate.

  PMID 37351564 New England Journal of Medicine
• Study in people2025
  Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1)

  The large trial agreed with the small one, though the average loss came out lower. Over three thousand adults took the highest dose of the tablet or a dummy tablet for about seventeen months. Those on the drug lost 11.2 percent of their weight on average, against 2.1 percent on the dummy. More than a third lost at least 15 percent of their starting weight. The figure quoted is the cautious one, which counts everybody, including the people who quit.

  Phase 3, 3,127 adults: 11.2% weight loss at 72 weeks on 36 mg versus 2.1% with placebo (treatment-regimen estimand); 36% lost 15% or more.

  PMID 40960239 New England Journal of Medicine
• Study in people2025
  Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1)

  In people early in type 2 diabetes, the tablet pulled average blood sugar down hard. Adults took orforglipron or a dummy tablet for about nine months. Their three month average blood sugar fell by 1.24 to 1.48 points, depending on the dose. On the dummy it fell 0.41 points. That is a large move for a diabetes drug you swallow. These people were early in the disease, so this does not say what happens after years of it.

  Phase 3: HbA1c fell 1.24 to 1.48 points at 40 weeks versus 0.41 with placebo.

  PMID 40544435 New England Journal of Medicine
• Study in people2026
  FDA approves Lilly's Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions

  The tablet was approved for weight loss, and this is the company saying so itself. It quotes a loss of 12.4 percent of body weight, about 27.3 pounds, on the highest dose. That figure comes from the more flattering of the two ways the trial was counted, the one that measures people while they are still taking the drug. The published trial reports a lower number. This is a press release written to sell, not a study.

  April 1, 2026 approval announcement; quotes 12.4% (27.3 lb) weight loss on the highest dose in ATTAIN-1 by the efficacy estimand.

  Source Eli Lilly press release
• Study in people2026
  NDA 220934 approval letter: Foundayo (orforglipron) tablets

  This is the regulator saying yes, in its own letter. It clears the tablet for long term weight management in adults with obesity, and in adults carrying extra weight who also have a weight related health problem. The company filed the application in January 2026. A letter like this records a decision. It is not evidence in itself, and what the drug actually does sits in the trials underneath it.

  FDA approval letter for chronic weight management in adults with obesity or overweight with a weight-related comorbidity; NDA received January 20, 2026.

  Source FDA (Drugs@FDA)
• Study in people2026
  Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial.

  A pill in this drug class produced real weight loss in people with both obesity and type 2 diabetes. 1,613 adults took one of three doses or a dummy pill for about seventeen months. Weight fell by roughly 5, 7 and 10 percent as the dose rose, against about 2 percent on the dummy. More people quit for side effects on the drug. Ten people died, six on drug and four on dummy, judged unrelated. Eli Lilly funded it, and some authors are employees who hold its stock.

  1,613 adults with obesity and type 2 diabetes across 136 sites in ten countries, 72 weeks. Weight change by the treatment-regimen estimand was -5.1, -7.0 and -9.6 percent on 6, 12 and 36 mg against -2.5 percent on placebo, all p<0.0001. Discontinuation for adverse events 6.1 to 9.9 percent against 4.1 percent. Ten deaths, six on drug and four on placebo, all judged unrelated except one placebo case and one 12 mg case for which no treatment-related association was reported. Funded by Eli Lilly, with employee-shareholder authors.

  PMID 41275875 The Lancet
• Study in people2026
  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.

  It beat the rival pill on blood sugar and lost to it on side effects. 962 adults on metformin were sorted by chance to orforglipron or dapagliflozin for about ten months. Average blood sugar fell further on orforglipron at every dose. Stomach and bowel trouble was the price: roughly half that group had it, against one in eight on dapagliflozin. Around three times as many stopped their tablets. Nobody had a dangerous blood sugar low. Everyone knew which drug they were on. Eli Lilly paid for the trial.

  962 adults on metformin, 40 weeks, open label with the orforglipron dose blinded. HbA1c fell 1.23, 1.50 and 1.56 percentage points on 3, 12 and 36 mg against 0.81 on dapagliflozin 10 mg, all treatment differences p<0.0001. Tolerability ran the other way: gastrointestinal events in 46 to 54 percent against 12 percent, and study drug discontinuation in 15 to 20 percent against 6 percent. No severe hypoglycaemia. Funded by Eli Lilly.

  PMID 42259339 The Lancet
• Study in people2026
  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.

  Head to head against the rival pill, it controlled blood sugar better and was harder to put up with. 1,698 adults on metformin took orforglipron or oral semaglutide for a year. Average blood sugar fell further on orforglipron at both dose pairings. Tolerability went the other way every time. Roughly six in ten had stomach and bowel side effects, against four to five in ten. About twice as many quit over side effects, and resting pulse rose more. Everyone knew which drug they were taking. Eli Lilly funded it.

  1,698 adults on metformin, 52 weeks, head to head against oral semaglutide. From a baseline HbA1c of 8.3 percent, orforglipron 12 mg gave -1.71 and 36 mg -1.91 against semaglutide 7 mg -1.23 and 14 mg -1.47, meeting non-inferiority and then superiority at both pairings. Orforglipron was worse on tolerability at every comparison: gastrointestinal events 58 to 59 percent against 37 to 45 percent, discontinuation for adverse events 9 to 10 percent against 4 to 5 percent, pulse rise 3.7 and 4.7 bpm against 1.0 and 1.5. Open label, funded by Eli Lilly.

  PMID 41765029 The Lancet
• Study in people2026
  Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial.

  Switching from an injection to this pill held most of the lost weight off, though not all. 376 people who had lost weight on tirzepatide or semaglutide were sorted by chance onto orforglipron or a dummy pill for a year. Among those who had already levelled off, the pill held about three quarters of what they had lost. On the dummy it was a third to a half. The authors name the gap themselves: no group stayed on the injection, and the trial ran only a year.

  376 people who had been on tirzepatide (205) or semaglutide (171) in SURMOUNT-5, randomized to orforglipron or placebo for 52 weeks. Among those reaching a weight plateau, the tirzepatide cohort held 74.7 percent of its weight reduction against 49.2 percent on placebo and the semaglutide cohort 79.3 percent against 37.6 percent. The authors state the limitations themselves: no arm continued the injectable, and the trial lasted one year.

  PMID 42120723 Nature Medicine
• Study in people2026
  Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials.

  Pooled liver data across the whole late-stage programme show no liver signal. 11,220 people were combined from seven trials, about 6,900 on orforglipron and 4,300 on something else, followed for up to two years. Six people in each half hit the liver enzyme threshold that triggers concern, and every orforglipron case had another explanation. None met the standard that marks true drug-caused liver injury. Liver enzymes fell on average. This is the manufacturer analysing its own trials.

  11,220 participants pooled across seven phase 3 trials, 6,920 on orforglipron and 4,300 on placebo, oral semaglutide, dapagliflozin or insulin glargine, up to 104 weeks including safety follow-up. Six orforglipron and six comparator participants (0.1 percent each) reached ALT or AST at three times the upper limit of normal with bilirubin at twice it; alternative causes explained all orforglipron cases and none met Hy's Law. Aminotransferases fell on average.

  PMID 42338042 Diabetes, Obesity and Metabolism
• Study in people2026
  A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Orforglipron on the Incidence of Major Adverse Cardiovascular Events in Participants With Established Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease

  This is the trial that would show whether the drug prevents heart attacks and deaths, and it is still running. It started in December 2025, is recruiting now, expects about 7,140 participants, and is not due to finish its main measurement until August 2031. Nothing has been published from it. Until it reports, no benefit to survival, heart attack or stroke has been shown for orforglipron. The weight and blood sugar results do not stand in for that. Eli Lilly is the sponsor.

  The cardiovascular outcomes trial, started December 2025, recruiting, with an estimated 7,140 participants and estimated primary completion in August 2031. Until it reports, no mortality or major adverse cardiovascular event benefit has been demonstrated for orforglipron, and none should be inferred from the weight and HbA1c results.

  NCT07241390 ClinicalTrials.gov, Eli Lilly and Company (ATTAIN-Outcomes)