parallel randomized trial
ACHIEVE-5
A 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 Inhibitor
Design
Conduct and analysis
Arms
| Arm | Treatment | Background | Randomized | Analyzed | Completed treatment |
|---|---|---|---|---|---|
| A1 | Placebo Placebo | insulin glargine U100 with or without metformin or SGLT2 inhibitor; lifestyle: not reported | 141 | 141 | |
| A2 | Orforglipron 3 mg oral once daily Orforglipron 3 mg QD | insulin glargine with or without metformin or SGLT2 inhibitor; lifestyle: not reported | 137 | 137 | |
| A3 | Orforglipron 12 mg oral once daily Orforglipron 12 mg QD | insulin glargine with or without metformin or SGLT2 inhibitor; lifestyle: not reported | 132 | 132 | |
| A4 | Orforglipron 36 mg oral once daily Orforglipron 36 mg QD | insulin glargine with or without metformin or SGLT2 inhibitor; lifestyle: not reported | 136 | 136 |
Baseline characteristics
As printed in the trial reports or registry, per arm or for the whole trial.
| Characteristic | Statistic | Placebo A1 | Orforglipron 3 mg oral once daily A2 | Orforglipron 12 mg oral once daily A3 | Orforglipron 36 mg oral once daily A4 | Whole trial ALL |
|---|---|---|---|---|---|---|
| age: 65 or older | n | 54 | 43 | 52 | 48 | |
| age | mean (years) | 60.2 | ||||
| age | sd (years) | 10.1 | ||||
| asian | n | 36 | 35 | 33 | 36 | |
| black | n | 13 | 15 | 12 | 13 | |
| bmi | mean (kg/m2) | 30.8 | ||||
| bmi | sd (kg/m2) | 6.1 | ||||
| diabetes duration | mean (years) | 15.0 | ||||
| diabetes duration | sd (years) | 8.3 | ||||
| egfr | mean (mL/min/1.73 m2) | 78.8 | ||||
| egfr | sd (mL/min/1.73 m2) | 23.4 | ||||
| female | n | 75 | 65 | 55 | 62 | |
| hba1c | mean (percent) | 8.5 | ||||
| hba1c | sd (percent) | 0.95 | ||||
| hispanic | n | 59 | 53 | 55 | 59 | |
| other race american indian | n | 1 | 0 | 1 | 0 | |
| other race multiple | n | 5 | 5 | 7 | 6 | |
| other race pacific islander | n | 0 | 0 | 0 | 1 | |
| waist | mean (cm) | 104.5 | ||||
| waist | sd (cm) | 14.2 | ||||
| weight | mean (kg) | 85.2 | ||||
| weight | sd (kg) | 19.2 | ||||
| white | n | 82 | 80 | 77 | 80 |
Analyses this trial contributes to
- HbA1c changeType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- HbA1c changeType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- HbA1c below 7 percentType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- HbA1c below 7 percentType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- Systolic blood pressure changeType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- Systolic blood pressure changeType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- Percent body weight changeType 2 diabetes (adults); weeks 40 to 104 (target week 68); network meta-analysis
- Percent body weight changeType 2 diabetes (adults); weeks 40 to 104 (target week 68); network meta-analysis
- Weight loss of 5 percent or moreType 2 diabetes (adults); weeks 40 to 104 (target week 68); network meta-analysis
- Weight loss of 5 percent or moreType 2 diabetes (adults); weeks 40 to 104 (target week 68); network meta-analysis
- Weight loss of 10 percent or moreType 2 diabetes (adults); weeks 40 to 104 (target week 68); descriptive only
- Weight loss of 10 percent or moreType 2 diabetes (adults); weeks 40 to 104 (target week 68); descriptive only
- Weight loss of 15 percent or moreType 2 diabetes (adults); weeks 40 to 104 (target week 68); descriptive only
- Weight loss of 15 percent or moreType 2 diabetes (adults); weeks 40 to 104 (target week 68); descriptive only
- Acute kidney injuryType 2 diabetes (adults); longest follow-up; network meta-analysis
- Acute kidney injuryType 2 diabetes (adults); longest follow-up; descriptive only
- SF-36 physical component summary changeType 2 diabetes (adults); weeks 20 to 130 (target week 52); network meta-analysis
- SF-36 physical component summary changeType 2 diabetes (adults); weeks 20 to 130 (target week 52); network meta-analysis
- Serious adverse eventsType 2 diabetes (adults); longest follow-up; network meta-analysis
- Serious adverse eventsType 2 diabetes (adults); longest follow-up; network meta-analysis
- NauseaType 2 diabetes (adults); longest follow-up; network meta-analysis
- NauseaType 2 diabetes (adults); longest follow-up; network meta-analysis
- VomitingType 2 diabetes (adults); longest follow-up; network meta-analysis
- VomitingType 2 diabetes (adults); longest follow-up; network meta-analysis
- DiarrheaType 2 diabetes (adults); longest follow-up; network meta-analysis
- DiarrheaType 2 diabetes (adults); longest follow-up; network meta-analysis
- ConstipationType 2 diabetes (adults); longest follow-up; network meta-analysis
- ConstipationType 2 diabetes (adults); longest follow-up; network meta-analysis
Results
115 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
HbA1c change (7 lines; O01)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | change | -0.77 percent | 0.078 | 141 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 | change | -1.54 percent | 0.097 | 137 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 vs A1 | md | -0.77 percent | -1.01 to -0.52 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | change | -2.05 percent | 0.098 | 132 | hypothetical; randomized; registry:outcomes | |
| 40 | A3 vs A1 | md | -1.28 percent | -1.52 to -1.03 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | change | -1.90 percent | 0.111 | 136 | hypothetical; randomized; registry:outcomes | |
| 40 | A4 vs A1 | md | -1.13 percent | -1.39 to -0.86 | hypothetical; randomized; registry:outcomes |
Body weight change in kilograms (diabetes) (7 lines; O02)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | change | 0.5 kg | 0.39 | 141 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 | change | -2.2 kg | 0.48 | 137 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 vs A1 | md | -2.6 kg | -3.8 to -1.4 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | change | -5.0 kg | 0.49 | 132 | hypothetical; randomized; registry:outcomes | |
| 40 | A3 vs A1 | md | -5.5 kg | -6.7 to -4.3 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | change | -5.2 kg | 0.64 | 136 | hypothetical; randomized; registry:outcomes | |
| 40 | A4 vs A1 | md | -5.6 kg | -7.1 to -4.2 | hypothetical; randomized; registry:outcomes |
HbA1c below 7 percent (7 lines; O03)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | responders | 23.69 | 141 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 | responders | 60.74 | 137 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 vs A1 | rd | 37.04 | 26.67 to 47.42 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | responders | 80.76 | 132 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 vs A1 | rd | 57.07 | 47.48 to 66.66 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | responders | 69.16 | 136 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 vs A1 | rd | 45.47 | 35.34 to 55.60 | hypothetical; randomized; registry:outcomes |
Level 2 or 3 hypoglycemia (participants) (4 lines; O04)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 140 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A2 | events | 0 / 137 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A3 | events | 2 / 132 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A4 | events | 1 / 135 | not stated; safety; hypoglycaemia; registry:adverse_events |
Systolic blood pressure change (7 lines; O05)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | change | 0.0 mmHg | 1.03 | 141 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 | change | -1.9 mmHg | 0.94 | 137 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 vs A1 | md | -1.9 mmHg | -4.6 to 0.9 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | change | -3.2 mmHg | 1.13 | 132 | hypothetical; randomized; registry:outcomes | |
| 40 | A3 vs A1 | md | -3.2 mmHg | -6.2 to -0.2 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | change | -2.2 mmHg | 1.26 | 136 | hypothetical; randomized; registry:outcomes | |
| 40 | A4 vs A1 | md | -2.2 mmHg | -5.4 to 1.0 | hypothetical; randomized; registry:outcomes |
Percent body weight change (7 lines; O10)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | percent change | 0.6 percent | 0.44 | 141 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 | percent change | -2.7 percent | 0.52 | 137 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 vs A1 | md | -3.3 percent | -4.6 to -2.0 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | percent change | -5.8 percent | 0.58 | 132 | hypothetical; randomized; registry:outcomes | |
| 40 | A3 vs A1 | md | -6.4 percent | -7.8 to -5.0 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | percent change | -6.1 percent | 0.68 | 136 | hypothetical; randomized; registry:outcomes | |
| 40 | A4 vs A1 | md | -6.8 percent | -8.4 to -5.2 | hypothetical; randomized; registry:outcomes |
Weight loss of 5 percent or more (7 lines; O11A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | responders | 16.10 | 141 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 | responders | 35.42 | 137 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 vs A1 | rd | 19.32 | 9.12 to 29.53 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | responders | 52.61 | 132 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 vs A1 | rd | 36.51 | 25.97 to 47.05 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | responders | 50.56 | 136 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 vs A1 | rd | 34.46 | 23.62 to 45.29 | hypothetical; randomized; registry:outcomes |
Weight loss of 10 percent or more (7 lines; O11B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | responders | 4.24 | 141 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 | responders | 15.70 | 137 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 vs A1 | rd | 11.46 | 4.42 to 18.50 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | responders | 23.34 | 132 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 vs A1 | rd | 19.09 | 10.89 to 27.30 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | responders | 27.38 | 136 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 vs A1 | rd | 23.14 | 14.33 to 31.96 | hypothetical; randomized; registry:outcomes |
Weight loss of 15 percent or more (7 lines; O11C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | responders | 2.52 | 141 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 | responders | 6.18 | 137 | hypothetical; randomized; registry:outcomes | ||
| 40 | A2 vs A1 | rd | 3.66 | -1.37 to 8.69 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 vs A1 | rd | 7.38 | 1.42 to 13.34 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | responders | 9.90 | 132 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | responders | 14.12 | 136 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 vs A1 | rd | 11.60 | 4.64 to 18.56 | hypothetical; randomized; registry:outcomes |
Acute kidney injury (4 lines; O121)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 140 | not stated; safety; acute kidney injury; registry:adverse_events | ||||
| A2 | events | 0 / 137 | not stated; safety; acute kidney injury; registry:adverse_events | ||||
| A3 | events | 0 / 132 | not stated; safety; acute kidney injury; registry:adverse_events | ||||
| A4 | events | 1 / 135 | not stated; safety; acute kidney injury; registry:adverse_events |
All cause mortality (4 lines; O20)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 140 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 0 / 137 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 132 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 1 / 135 | not stated; safety; registry:adverse_events |
SF-36 physical component summary change (7 lines; O24A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 40 | A1 | change | 0.71 points | 0.491 | 141 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 | change | 0.47 points | 0.496 | 137 | hypothetical; randomized; registry:outcomes | |
| 40 | A2 vs A1 | md | -0.24 points | -1.57 to 1.10 | hypothetical; randomized; registry:outcomes | ||
| 40 | A3 | change | 1.07 points | 0.592 | 132 | hypothetical; randomized; registry:outcomes | |
| 40 | A3 vs A1 | md | 0.37 points | -1.10 to 1.84 | hypothetical; randomized; registry:outcomes | ||
| 40 | A4 | change | 0.35 points | 0.572 | 136 | hypothetical; randomized; registry:outcomes | |
| 40 | A4 vs A1 | md | -0.35 points | -1.78 to 1.07 | hypothetical; randomized; registry:outcomes |
Serious adverse events (4 lines; O25)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 6 / 140 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 7 / 137 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 9 / 132 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 10 / 135 | not stated; safety; registry:adverse_events |
Discontinuation due to adverse events (4 lines; O26)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 2 / 141 | not stated; randomized; registry:flow | ||||
| A2 | events | 2 / 137 | not stated; randomized; registry:flow | ||||
| A3 | events | 1 / 132 | not stated; randomized; registry:flow | ||||
| A4 | events | 4 / 136 | not stated; randomized; registry:flow |
Nausea (4 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 6 / 140 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 29 / 137 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 37 / 132 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 41 / 135 | not stated; safety; registry:adverse_events |
Vomiting (8 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 140 | not stated; safety; registry:adverse_events | ||||
| A1 | events | 0 / 140 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 11 / 137 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 0 / 137 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 20 / 132 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 132 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 29 / 135 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 1 / 135 | not stated; safety; registry:adverse_events |
Diarrhea (4 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 10 / 140 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 26 / 137 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 18 / 132 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 22 / 135 | not stated; safety; registry:adverse_events |
Constipation (4 lines; O27D)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 6 / 140 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 20 / 137 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 15 / 132 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 10 / 135 | not stated; safety; registry:adverse_events |
Gallbladder and biliary disease (8 lines; O28)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 140 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A1 | events | 0 / 140 | not stated; safety; hyperplastic cholecystopathy; registry:adverse_events | ||||
| A2 | events | 0 / 137 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 0 / 137 | not stated; safety; hyperplastic cholecystopathy; registry:adverse_events | ||||
| A3 | events | 1 / 132 | not stated; safety; hyperplastic cholecystopathy; registry:adverse_events | ||||
| A3 | events | 1 / 132 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A4 | events | 0 / 135 | not stated; safety; hyperplastic cholecystopathy; registry:adverse_events | ||||
| A4 | events | 2 / 135 | not stated; safety; cholelithiasis; registry:adverse_events |
Acute pancreatitis (4 lines; O29)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 140 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A2 | events | 0 / 137 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A3 | events | 0 / 132 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A4 | events | 1 / 135 | not stated; safety; pancreatitis acute; registry:adverse_events |