Oral peptide GLP-1 receptor agonist
Semaglutide 14 mg oral once daily (original tablet)
SEMA_PO_14MG_QD
A prespecified sensitivity analysis pools 3 mg with reformulated 1.5 mg; 7 mg with 4 mg; and 14 mg with 9 mg only.
Related
- All doses pooled: Semaglutide tablet
- Semaglutide 20 mg tablet once daily
- Semaglutide 40 mg tablet once daily
- Semaglutide 3 mg oral once daily (original tablet)
- Semaglutide 7 mg oral once daily (original tablet)
- Semaglutide oral once daily (original tablet), flexible dose: 3, 7 or 14 mg adjusted by HbA1c and tolerability
- Semaglutide 50 mg oral once daily (higher dose oral program)
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 20 to 36 (target week 26) | Placebo | MD -1.25 (-1.48 to -1.00) | 0.77 |
| Type 2 diabetes (adults) | HbA1c change | weeks 36 to 64 (target week 52) | Placebo | MD -1.35 (-1.60 to -1.02) | 0.58 |
| Type 2 diabetes (adults) | HbA1c change | weeks 36 to 64 (target week 52) | Placebo | MD -1.08 (-1.46 to -0.59) | 0.92 |
| Type 2 diabetes (adults) | HbA1c change | weeks 20 to 36 (target week 26) | Placebo | MD -1.02 (-1.34 to -0.69) | 0.81 |
| Type 2 diabetes (adults) | HbA1c change | weeks 20 to 36 (target week 26) | Placebo | MD -1.77 (-3.73 to 0.31) | 0.67 |
| Type 2 diabetes (adults) | HbA1c change | weeks 20 to 36 (target week 26) | Placebo | MD -1.39 (-1.59 to -1.19) | 0.97 |
| Type 2 diabetes (adults) | HbA1c change | weeks 36 to 64 (target week 52) | Placebo | MD -1.46 (-2.19 to -0.25) | 0.79 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 20 to 36 (target week 26) | Placebo | MD -3.32 (-4.10 to -2.57) | 0.78 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 36 to 64 (target week 52) | Placebo | MD -3.34 (-4.86 to -1.69) | 0.96 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 36 to 64 (target week 52) | Placebo | MD -3.48 (-5.94 to -0.65) | 0.64 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 20 to 36 (target week 26) | Placebo | MD -1.38 (-5.12 to 3.27) | 0.59 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 20 to 36 (target week 26) | Placebo | MD -3.59 (-4.41 to -2.73) | 0.97 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 36 to 64 (target week 52) | Placebo | MD -1.84 (-6.02 to 2.65) | 0.82 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 20 to 36 (target week 26) | Placebo | MD -2.36 (-3.39 to -1.37) | 0.99 |
| Type 2 diabetes (adults) | Body weight change in kilograms (diabetes) | weeks 20 to 36 (target week 26) | Placebo | MD -2.57 (-5.34 to 0.40) | 0.95 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 20 to 36 (target week 26) | Placebo | OR 11.07 (3.68 to 23.26) | 0.73 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 36 to 64 (target week 52) | Placebo | OR 7.28 (1.90 to 17.60) | 0.89 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 36 to 64 (target week 52) | Placebo | OR 6.83 (2.50 to 13.89) | 0.86 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 20 to 36 (target week 26) | Placebo | OR 9.75 (4.10 to 20.38) | 0.94 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 20 to 36 (target week 26) | Placebo | OR 12.26 (3.55 to 34.10) | 0.74 |
| Type 2 diabetes (adults) | HbA1c below 7 percent | weeks 36 to 64 (target week 52) | Placebo | OR 13.00 (2.23 to 46.88) | 0.92 |
| Type 2 diabetes (adults) | Level 2 or 3 hypoglycemia (participants) | longest follow-up | Placebo | HR 0.24 (0.00 to 7.93) | 0.58 |
| Type 2 diabetes (adults) | Level 2 or 3 hypoglycemia (participants) | longest follow-up | Placebo | HR 1.25 (0.42 to 3.74) | 0.54 |
| Type 2 diabetes (adults) | Level 2 or 3 hypoglycemia (participants) | longest follow-up | Placebo | HR 0.95 (0.49 to 1.82) | 0.50 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 20 to 36 (target week 26) | Placebo | MD -4.17 (-5.89 to -2.41) | 0.78 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 36 to 64 (target week 52) | Placebo | MD -2.94 (-5.61 to -0.11) | 0.91 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 36 to 64 (target week 52) | Placebo | MD -2.10 (-5.54 to 1.42) | 0.47 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 36 to 64 (target week 52) | Placebo | MD -2.84 (-7.83 to 3.22) | 0.54 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 20 to 36 (target week 26) | Placebo | MD -1.40 (-3.93 to 0.92) | 0.85 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 20 to 36 (target week 26) | Placebo | MD -2.02 (-13.03 to 10.30) | 0.67 |
| Type 2 diabetes (adults) | Systolic blood pressure change | weeks 64 to 130 (target week 104) | Placebo | MD -2.97 (-14.49 to 9.17) | 0.68 |
| Type 2 diabetes (adults) | Percent body weight change | weeks 40 to 104 (target week 68) | Placebo | MD -3.86 (-6.15 to -1.32) | 0.93 |
| Type 2 diabetes (adults) | Percent body weight change | weeks 20 to 40 (target week 26) | Placebo | MD -4.27 (-5.98 to -2.39) | 0.99 |
| Type 2 diabetes (adults) | Percent body weight change | weeks 20 to 40 (target week 26) | Placebo | MD -2.97 (-10.66 to 5.13) | 0.62 |
| Type 2 diabetes (adults) | Percent body weight change | weeks 20 to 40 (target week 26) | Placebo | MD -2.94 (-9.36 to 4.28) | 0.71 |
| Type 2 diabetes (adults) | Percent body weight change | weeks 20 to 40 (target week 26) | Placebo | MD -2.73 (-4.51 to -0.68) | 0.99 |
| Type 2 diabetes (adults) | Weight loss of 5 percent or more | weeks 20 to 40 (target week 26) | Placebo | OR 8.91 (3.28 to 21.69) | 0.73 |
| Type 2 diabetes (adults) | Weight loss of 5 percent or more | weeks 40 to 104 (target week 68) | Placebo | OR 6.09 (2.18 to 15.13) | 0.97 |
| Type 2 diabetes (adults) | Weight loss of 5 percent or more | weeks 20 to 40 (target week 26) | Placebo | OR 7.53 (2.73 to 17.78) | 0.99 |
| Type 2 diabetes (adults) | Weight loss of 5 percent or more | weeks 40 to 104 (target week 68) | Placebo | OR 4.83 (1.94 to 10.39) | 0.91 |
| Type 2 diabetes (adults) | Weight loss of 5 percent or more | weeks 20 to 40 (target week 26) | Placebo | OR 4.90 (2.18 to 12.30) | 1.00 |
| Type 2 diabetes (adults) | Weight loss of 10 percent or more | weeks 20 to 40 (target week 26) | Placebo | OR 12.97 (3.24 to 55.34) | 0.85 |
| Type 2 diabetes (adults) | Weight loss of 10 percent or more | weeks 40 to 104 (target week 68) | Placebo | OR 5.61 (1.63 to 21.56) | 0.86 |
| Type 2 diabetes (adults) | Weight loss of 10 percent or more | weeks 20 to 40 (target week 26) | Placebo | OR 11.05 (3.10 to 43.87) | 0.98 |
| Type 2 diabetes (adults) | Weight loss of 10 percent or more | weeks 40 to 104 (target week 68) | Placebo | OR 4.99 (1.75 to 14.23) | 0.91 |
| Type 2 diabetes (adults) | Weight loss of 10 percent or more | weeks 20 to 40 (target week 26) | Placebo | OR 11.55 (3.44 to 49.74) | 0.99 |
| Type 2 diabetes (adults) | All cause mortality | longest follow-up | Placebo | HR 0.52 (0.28 to 0.97) | 0.95 |
| Type 2 diabetes (adults) | Three point MACE | longest follow-up | Placebo | HR 0.79 (0.43 to 1.47) | 0.64 |
| Type 2 diabetes (adults) | Hospitalization for heart failure | longest follow-up | Placebo | HR 0.85 (0.38 to 1.87) | 0.63 |
| Type 2 diabetes (adults) | SF-36 physical component summary change | weeks 20 to 130 (target week 52) | Placebo | MD -0.10 (-0.86 to 0.65) | 0.41 |
| Type 2 diabetes (adults) | SF-36 physical component summary change | weeks 20 to 130 (target week 52) | Placebo | MD 0.65 (-0.40 to 1.77) | 0.45 |
| Type 2 diabetes (adults) | SF-36 physical component summary change | weeks 20 to 130 (target week 52) | Semaglutide 3 mg oral once daily (original tablet) | MD -0.18 (-7.55 to 7.33) | 0.43 |
| Type 2 diabetes (adults) | Serious adverse events | longest follow-up | Placebo | HR 0.84 (0.70 to 1.01) | 0.59 |
| Type 2 diabetes (adults) | Discontinuation due to adverse events | longest follow-up | Placebo | HR 1.94 (1.37 to 2.76) | 0.43 |
| Type 2 diabetes (adults) | Nausea | longest follow-up | Placebo | HR 2.99 (2.35 to 3.82) | 0.46 |
| Type 2 diabetes (adults) | Vomiting | longest follow-up | Placebo | HR 3.97 (2.88 to 5.56) | 0.36 |
| Type 2 diabetes (adults) | Diarrhea | longest follow-up | Placebo | HR 1.89 (1.51 to 2.38) | 0.42 |
| Type 2 diabetes (adults) | Constipation | longest follow-up | Placebo | HR 2.30 (1.66 to 3.18) | 0.36 |
| Type 2 diabetes (adults) | Discontinuation due to gastrointestinal adverse events | longest follow-up | Placebo | HR 4.59 (1.67 to 12.22) | 0.26 |
| Type 2 diabetes (adults) | Gallbladder and biliary disease | longest follow-up | Placebo | HR 0.14 (0.00 to 3.44) | 0.80 |
| Type 2 diabetes (adults) | Acute pancreatitis | longest follow-up | Placebo | HR 0.22 (0.02 to 1.65) | 0.75 |
| Type 2 diabetes (adults) | Diabetic retinopathy complications | longest follow-up | Placebo | HR 1.35 (0.40 to 5.11) | 0.46 |
| Type 2 diabetes (adults) | Pancreatic cancer | longest follow-up | Placebo | HR 0.52 (0.04 to 6.03) | 0.61 |
| Type 2 diabetes (adults) | Any cancer | longest follow-up | Placebo | HR 2.60 (0.18 to 33.52) | 0.29 |
| Type 2 diabetes (adults) | Acute kidney injury | longest follow-up | Placebo | HR 0.61 (0.06 to 4.89) | 0.52 |
| Overweight or obesity without diabetes (adults) | Serious adverse events | longest follow-up | Placebo | HR 0.75 (0.06 to 5.26) | 0.61 |
| Overweight or obesity without diabetes (adults) | Discontinuation due to adverse events | longest follow-up | Placebo | HR 1.37 (0.38 to 4.31) | 0.60 |
| Overweight or obesity without diabetes (adults) | Nausea | longest follow-up | Placebo | HR 1.52 (0.63 to 3.47) | 0.82 |
| Overweight or obesity without diabetes (adults) | Vomiting | longest follow-up | Placebo | HR 2.89 (0.80 to 9.87) | 0.63 |
| Overweight or obesity without diabetes (adults) | Diarrhea | longest follow-up | Placebo | HR 0.82 (0.26 to 2.26) | 0.80 |
| Overweight or obesity without diabetes (adults) | Constipation | longest follow-up | Placebo | HR 1.02 (0.25 to 3.48) | 0.72 |
| Chronic kidney disease with diabetes | Serious adverse events | longest follow-up | Placebo | HR 0.98 (0.28 to 3.68) | 0.62 |
| Chronic kidney disease with diabetes | Nausea | longest follow-up | Placebo | HR 2.63 (0.77 to 8.25) | 0.49 |
| Chronic kidney disease with diabetes | Vomiting | longest follow-up | Placebo | HR 8.21 (1.64 to 48.49) | 0.23 |
| Chronic kidney disease with diabetes | Diarrhea | longest follow-up | Placebo | HR 2.76 (0.65 to 10.66) | 0.45 |
| Chronic kidney disease with diabetes | Constipation | longest follow-up | Placebo | HR 3.07 (0.75 to 12.36) | 0.31 |
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
- NCT05579977A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, DOSE RANGING, DOSE FINDING, PARALLEL GROUP STUDY TO ASSESS EFFICACY AND SAFETY OF PF-07081532, AND OPEN LABEL ORAL SEMAGLUTIDE, IN ADULTS WITH TYPE 2 DIABETES MELLITUS (T2DM) INADEQUATELY CONTROLLED ON METFORMIN, AND SEPARATELY PF-07081532 COMPARED TO MATCHING PLACEBO IN ADULTS WITH OBESITY BUT WITHOUT T2DM2022 · 902 randomized · 32 weeks
- PIONEER 11China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only2019 · 521 randomized · 26 weeks
- PIONEER 12China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus Treated With Metformin2019 · 1,441 randomized · 26 weeks
- PIONEER 9Dose-response, Safety and Efficacy of Oral Semaglutide Versus Placebo and Versus Liraglutide, All as Monotherapy in Japanese Subjects With Type 2 Diabetes2017 · 243 randomized · 52 weeks
- PIONEER 6A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes2017 · 3,183 randomized
- PIONEER 10Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD in Japanese Subjects With Type 2 Diabetes2017 · 458 randomized · 52 weeks
- PIONEER 8Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin. A 52-week, Randomised, Double-blind, Placebo-controlled Trial (PIONEER 8 - Insulin add-on)2017 · 731 randomized · 52 weeks
- PIONEER 1Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only.2016 · 703 randomized · 26 weeks
- PIONEER 4Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus2016 · 711 randomized · 52 weeks
- PIONEER 5Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment2016 · 324 randomized · 26 weeks
- PIONEER 3Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes2016 · 1,864 randomized · 78 weeks