Oral small molecule GLP-1 receptor agonist
Orforglipron tablet
ORFO_PO
Doses in this pooled treatment
- Orforglipron 12 mg oral once daily
- Orforglipron 36 mg oral once daily
- Orforglipron 6 mg oral once daily
- Orforglipron 3 mg oral once daily
- Orforglipron maximum tolerated dose tablet once daily
- Orforglipron 1 mg tablet once daily
- Orforglipron 14.5 mg tablet once daily
- Orforglipron 17.2 mg tablet once daily
- Orforglipron 0.8 mg tablet once daily
- Orforglipron 2.5 mg tablet once daily
- Orforglipron 5.5 mg tablet once daily
- Orforglipron 9 mg tablet once daily
- Orforglipron 24 mg oral once daily
- Orforglipron 45 mg oral once daily
Effects across outcomes
Bayesian random effects estimate against the comparator of each analysis (usually placebo), posterior median and 95% credible interval. Green: clearly better; red: clearly worse.
| Condition | Outcome | Window | Versus | Effect (95% CrI) | SUCRA |
|---|---|---|---|---|---|
| Type 2 diabetes (adults) | HbA1c change | weeks 36 to 64 (target week 52) | Placebo | MD -2.00 (-2.85 to -0.48) | 0.85 |
| Type 2 diabetes (adults) | HbA1c change | weeks 36 to 64 (target week 52) | Placebo | MD -1.05 (-1.93 to 0.02) | 0.67 |
| Type 2 diabetes (adults) | HbA1c change | weeks 36 to 64 (target week 52) | Placebo | MD -1.26 (-2.25 to -0.18) | 0.62 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 36 to 64 (target week 52) | Placebo | MD -6.97 (-11.48 to -1.35) | 0.83 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 36 to 64 (target week 52) | Placebo | MD -4.54 (-8.98 to 0.42) | 0.66 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 36 to 64 (target week 52) | Placebo | MD -4.34 (-9.30 to 0.99) | 0.67 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 36 to 64 (target week 52) | Placebo | OR 7.11 (1.20 to 23.45) | 0.52 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 36 to 64 (target week 52) | Placebo | OR 6.06 (1.15 to 19.50) | 0.91 |
| Type 2 diabetes (adults) | Level 2 or 3 hypoglycemia (participants) | longest follow-up | Placebo | HR 1.52 (0.07 to 68.91) | 0.50 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 36 to 64 (target week 52) | Placebo | MD -3.78 (-7.06 to -0.43) | 0.74 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 20 to 36 (target week 26) | Placebo | MD -2.27 (-6.29 to 1.86) | 0.35 |
| Type 2 diabetes (adults) | Percent body weight change | weeks 40 to 104 (target week 68) | Semaglutide tablet | MD -3.38 (-10.04 to 3.68) | 0.90 |
| Type 2 diabetes (adults) | Percent body weight change | weeks 40 to 104 (target week 68) | Placebo | MD -5.40 (-12.30 to 1.99) | 0.75 |
| Type 2 diabetes (adults) | Weight loss of 5 percent or more | weeks 40 to 104 (target week 68) | Placebo | OR 4.31 (1.37 to 11.83) | 0.72 |
| Type 2 diabetes (adults) | SF-36 physical component summary change | weeks 20 to 130 (target week 52) | Placebo | MD -0.22 (-1.04 to 0.63) | 0.27 |
| Type 2 diabetes (adults) | Serious adverse events | longest follow-up | Placebo | HR 1.20 (0.90 to 1.62) | 0.33 |
| Type 2 diabetes (adults) | Nausea | longest follow-up | Placebo | HR 4.84 (3.21 to 7.32) | 0.18 |
| Type 2 diabetes (adults) | Vomiting | longest follow-up | Placebo | HR 6.98 (4.26 to 11.72) | 0.15 |
| Type 2 diabetes (adults) | Diarrhea | longest follow-up | Placebo | HR 2.23 (1.71 to 3.02) | 0.27 |
| Type 2 diabetes (adults) | Constipation | longest follow-up | Placebo | HR 3.43 (2.52 to 4.81) | 0.15 |
| Type 2 diabetes (adults) | Gallbladder and biliary disease | longest follow-up | Placebo | HR 0.40 (0.00 to 29.61) | 0.62 |
| Type 2 diabetes (adults) | Acute pancreatitis | longest follow-up | Placebo | HR 0.68 (0.04 to 10.94) | 0.44 |
| Overweight or obesity without diabetes (adults) | Systolic blood pressure change | weeks 20 to 40 (target week 26) | Placebo | MD -6.73 (-18.52 to 5.31) | 0.77 |
| Overweight or obesity without diabetes (adults) | Percent body weight change | weeks 40 to 104 (target week 68) | Placebo | MD -8.56 (-15.85 to -0.83) | 0.30 |
| Overweight or obesity without diabetes (adults) | Percent body weight change | weeks 20 to 40 (target week 26) | Placebo | MD -9.03 (-16.72 to -0.84) | 0.68 |
| Overweight or obesity without diabetes (adults) | Serious adverse events | longest follow-up | Placebo | HR 1.12 (0.64 to 2.15) | 0.58 |
| Overweight or obesity without diabetes (adults) | Nausea | longest follow-up | Placebo | HR 3.85 (2.85 to 5.45) | 0.45 |
| Overweight or obesity without diabetes (adults) | Vomiting | longest follow-up | Placebo | HR 5.79 (3.07 to 10.49) | 0.43 |
| Overweight or obesity without diabetes (adults) | Diarrhea | longest follow-up | Placebo | HR 2.49 (1.47 to 4.25) | 0.38 |
| Overweight or obesity without diabetes (adults) | Constipation | longest follow-up | Placebo | HR 3.23 (1.94 to 5.62) | 0.29 |
| Weight maintenance after a GLP-1 receptor agonist containing run in | Nausea | longest follow-up | Placebo | HR 4.65 (1.00 to 18.33) | 0.12 |
| Weight maintenance after a GLP-1 receptor agonist containing run in | Vomiting | longest follow-up | Placebo | HR 2.36 (0.57 to 10.54) | 0.24 |
| Weight maintenance after a GLP-1 receptor agonist containing run in | Diarrhea | longest follow-up | Placebo | HR 0.98 (0.24 to 3.95) | 0.74 |
| Weight maintenance after a GLP-1 receptor agonist containing run in | Constipation | longest follow-up | Placebo | HR 3.30 (0.85 to 12.92) | 0.23 |
Trials
- ACHIEVE-3A Phase 3, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Oral Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-3)2023 · 1,698 randomized · 52 weeks
- ATTAIN-2A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral LY3502970 Compared With Placebo in Adult Participants With Obesity or Overweight and Type 2 Diabetes (ATTAIN-2)2023 · 1,613 randomized · 72 weeks
- ACHIEVE-5A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral Orforglipron Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor2023 · 546 randomized · 40 weeks
- ATTAIN-1A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral Orforglipron Compared With Placebo in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-1)2023 · 3,127 randomized · 72 weeks
- ACHIEVE-1A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone2023 · 559 randomized · 40 weeks
- NCT05086445A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3502970 in Japanese Participants With Type 2 Diabetes Mellitus2021 · 62 randomized · 12 weeks
- NCT05048719A Phase 2 Study of Once-Daily LY3502970 Compared With Placebo and Once-Weekly Dulaglutide in Participants With Type 2 Diabetes Mellitus2021 · 383 randomized · 26 weeks
- NCT05051579A Phase 2 Study of Once-Daily LY3502970 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities2021 · 272 randomized · 36 weeks