parallel randomized trial
NCT05048719
A Phase 2 Study of Once-Daily LY3502970 Compared With Placebo and Once-Weekly Dulaglutide in Participants With Type 2 Diabetes Mellitus
Design
Conduct and analysis
Arms
| Arm | Treatment | Background | Randomized | Analyzed | Completed treatment |
|---|---|---|---|---|---|
| A1 | Placebo Placebo | diet and exercise with or without metformin; lifestyle: not reported | 55 | 55 | |
| A2 | Orforglipron 3 mg oral once daily Orforglipron 3 mg | diet and exercise with or without metformin; lifestyle: not reported | 51 | ||
| A3 | Orforglipron 12 mg oral once daily Orforglipron 12 mg | diet and exercise with or without metformin; lifestyle: not reported | 56 | ||
| A4 | Orforglipron 24 mg oral once daily Orforglipron 24 mg | diet and exercise with or without metformin; lifestyle: not reported | 47 | ||
| A5 | Orforglipron 36 mg oral once daily Orforglipron 36 mg escalation 1 | diet and exercise with or without metformin; lifestyle: not reported | 27 | ||
| A6 | Orforglipron 36 mg oral once daily Orforglipron 36 mg escalation 2 | diet and exercise with or without metformin; lifestyle: not reported | 34 | ||
| A7 | Orforglipron 45 mg oral once daily Orforglipron 45 mg escalation 1 | diet and exercise with or without metformin; lifestyle: not reported | 31 | ||
| A8 | Orforglipron 45 mg oral once daily Orforglipron 45 mg escalation 2 | diet and exercise with or without metformin; lifestyle: not reported | 32 | ||
| A9 | Dulaglutide 1.5 mg subcutaneous once weekly Dulaglutide 1.5 mg | diet and exercise with or without metformin; lifestyle: not reported | 50 |
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 24 mg oral once daily A4 | Orforglipron 36 mg oral once daily A5 | Orforglipron 36 mg oral once daily A6 | Orforglipron 45 mg oral once daily A7 | Orforglipron 45 mg oral once daily A8 | Dulaglutide 1.5 mg subcutaneous once weekly A9 |
|---|---|---|---|---|---|---|---|---|---|---|
| age | mean (years) | 58.30 | 59.00 | 57.40 | 60.50 | 59.20 | 60.10 | 58.10 | 58.90 | 58.80 |
| age | sd (years) | 9.52 | 9.43 | 9.23 | 9.11 | 9.07 | 9.37 | 10.63 | 8.18 | 10.19 |
| asian | n | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 |
| black | n | 4 | 2 | 5 | 2 | 0 | 0 | 2 | 3 | 4 |
| bmi | mean (kg/m2) | 35.8 | 34.8 | 35.2 | 34.2 | 35.4 | ||||
| bmi | sd (kg/m2) | 6.2 | 7.5 | 6.3 | 7.9 | 8.0 | ||||
| female | n | 27 | 25 | 20 | 17 | 9 | 16 | 10 | 13 | 20 |
| hba1c | mean (percent) | 8.1 | 8.0 | 8.2 | 8.2 | 8.0 | 8.1 | 8.3 | 8.0 | 8.0 |
| hba1c | sd (percent) | 0.9 | 0.8 | 0.9 | 0.9 | 0.7 | 0.8 | 1.0 | 0.8 | 0.7 |
| hispanic | n | 14 | 7 | 15 | 5 | 6 | 7 | 7 | 6 | 7 |
| other american indian alaska native | n | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 |
| other multiple race | n | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
| waist | mean (cm) | 115.2 | 112.4 | 114.9 | 114.2 | 114.0 | ||||
| waist | sd (cm) | 12.4 | 18.1 | 11.2 | 15.0 | 16.4 | ||||
| weight | mean (kg) | 102.2 | 98.7 | 100.4 | 100.5 | 98.8 | ||||
| weight | sd (kg) | 18.9 | 25.4 | 17.6 | 22.0 | 22.1 | ||||
| white | n | 50 | 47 | 49 | 43 | 25 | 33 | 29 | 28 | 44 |
Analyses this trial contributes to
- Systolic blood pressure changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- Systolic blood pressure changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); 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
145 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
HbA1c change (17 lines; O01)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | -0.43 percent | 0.128 | 55 | not stated; modified itt; registry:outcomes | |
| 26 | A2 | change | -1.19 percent | 0.137 | 46 | not stated; modified itt; registry:outcomes | |
| 26 | A2 vs A1 | md | -0.77 percent | -1.13 to -0.40 | not stated; modified itt; registry:outcomes | ||
| 26 | A2 vs A9 | md | -0.09 percent | -0.47 to 0.28 | not stated; modified itt; registry:outcomes | ||
| 26 | A3 | change | -1.91 percent | 0.133 | 49 | not stated; modified itt; registry:outcomes | |
| 26 | A3 vs A1 | md | -1.49 percent | -1.85 to -1.12 | not stated; modified itt; registry:outcomes | ||
| 26 | A3 vs A9 | md | -0.81 percent | -1.18 to -0.44 | not stated; modified itt; registry:outcomes | ||
| 26 | A4 | change | -1.79 percent | 0.149 | 42 | not stated; modified itt; registry:outcomes | |
| 26 | A4 vs A1 | md | -1.36 percent | -1.75 to -0.98 | not stated; modified itt; registry:outcomes | ||
| 26 | A4 vs A9 | md | -0.69 percent | -1.08 to -0.30 | not stated; modified itt; registry:outcomes | ||
| 26 | A5 | change | -2.03 percent | 0.127 | 57 | not stated; modified itt; registry:outcomes | |
| 26 | A5 vs A1 | md | -1.60 percent | -1.96 to -1.25 | not stated; modified itt; registry:outcomes | ||
| 26 | A5 vs A9 | md | -0.93 percent | -1.29 to -0.57 | not stated; modified itt; registry:outcomes | ||
| 26 | A7 | change | -2.10 percent | 0.124 | 58 | not stated; modified itt; registry:outcomes | |
| 26 | A7 vs A1 | md | -1.67 percent | -2.02 to -1.32 | not stated; modified itt; registry:outcomes | ||
| 26 | A7 vs A9 | md | -1.00 percent | -1.36 to -0.64 | not stated; modified itt; registry:outcomes | ||
| 26 | A9 | change | -1.10 percent | 0.131 | 49 | not stated; modified itt; registry:outcomes |
Body weight change in kilograms (diabetes) (17 lines; O02)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | -2.2 kg | 0.74 | 55 | not stated; modified itt; registry:outcomes | |
| 26 | A2 | change | -3.7 kg | 0.79 | 50 | not stated; modified itt; registry:outcomes | |
| 26 | A2 vs A1 | md | -1.6 kg | -3.7 to 0.6 | not stated; modified itt; registry:outcomes | ||
| 26 | A2 vs A9 | md | 0.1 kg | -2.0 to 2.3 | not stated; modified itt; registry:outcomes | ||
| 26 | A3 | change | -6.5 kg | 0.76 | 53 | not stated; modified itt; registry:outcomes | |
| 26 | A3 vs A1 | md | -4.3 kg | -6.4 to -2.2 | not stated; modified itt; registry:outcomes | ||
| 26 | A3 vs A9 | md | -2.6 kg | -4.7 to -0.5 | not stated; modified itt; registry:outcomes | ||
| 26 | A4 | change | -9.7 kg | 0.85 | 46 | not stated; modified itt; registry:outcomes | |
| 26 | A4 vs A1 | md | -7.6 kg | -9.8 to -5.3 | not stated; modified itt; registry:outcomes | ||
| 26 | A4 vs A9 | md | -5.9 kg | -8.1 to -3.6 | not stated; modified itt; registry:outcomes | ||
| 26 | A5 | change | -9.5 kg | 0.73 | 57 | not stated; modified itt; registry:outcomes | |
| 26 | A5 vs A1 | md | -7.4 kg | -9.4 to -5.3 | not stated; modified itt; registry:outcomes | ||
| 26 | A5 vs A9 | md | -5.7 kg | -7.8 to -3.6 | not stated; modified itt; registry:outcomes | ||
| 26 | A7 | change | -10.1 kg | 0.71 | 62 | not stated; modified itt; registry:outcomes | |
| 26 | A7 vs A1 | md | -7.9 kg | -9.9 to -5.9 | not stated; modified itt; registry:outcomes | ||
| 26 | A7 vs A9 | md | -6.2 kg | -8.3 to -4.2 | not stated; modified itt; registry:outcomes | ||
| 26 | A9 | change | -3.9 kg | 0.76 | 50 | not stated; modified itt; registry:outcomes |
HbA1c below 7 percent (17 lines; O03)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | responders | 24.27 | 55 | not stated; modified itt; registry:outcomes | ||
| 26 | A2 | responders | 65.17 | 46 | not stated; modified itt; registry:outcomes | ||
| 26 | A2 vs A1 | or | 8.19 | 2.93 to 22.90 | not stated; modified itt; registry:outcomes | ||
| 26 | A2 vs A9 | or | 1.13 | 0.43 to 2.96 | not stated; modified itt; registry:outcomes | ||
| 26 | A3 | responders | 78.92 | 49 | not stated; modified itt; registry:outcomes | ||
| 26 | A3 vs A1 | or | 25.02 | 7.57 to 82.69 | not stated; modified itt; registry:outcomes | ||
| 26 | A3 vs A9 | or | 3.46 | 1.16 to 10.31 | not stated; modified itt; registry:outcomes | ||
| 26 | A4 | responders | 91.24 | 42 | not stated; modified itt; registry:outcomes | ||
| 26 | A4 vs A1 | or | 62.31 | 12.26 to 316.63 | not stated; modified itt; registry:outcomes | ||
| 26 | A4 vs A9 | or | 8.61 | 1.83 to 40.51 | not stated; modified itt; registry:outcomes | ||
| 26 | A5 | responders | 92.75 | 57 | not stated; modified itt; registry:outcomes | ||
| 26 | A5 vs A1 | or | 67.57 | 17.56 to 259.97 | not stated; modified itt; registry:outcomes | ||
| 26 | A5 vs A9 | or | 9.34 | 2.67 to 32.71 | not stated; modified itt; registry:outcomes | ||
| 26 | A7 | responders | 95.76 | 58 | not stated; modified itt; registry:outcomes | ||
| 26 | A7 vs A1 | or | 129.55 | 26.72 to 628.09 | not stated; modified itt; registry:outcomes | ||
| 26 | A7 vs A9 | or | 17.90 | 4.02 to 79.70 | not stated; modified itt; registry:outcomes | ||
| 26 | A9 | responders | 64.06 | 49 | not stated; modified itt; registry:outcomes |
Level 2 or 3 hypoglycemia (participants) (9 lines; O04)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 55 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A2 | events | 0 / 51 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A3 | events | 0 / 56 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A4 | events | 0 / 47 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A5 | events | 0 / 27 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A6 | events | 1 / 34 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A7 | events | 0 / 31 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A8 | events | 0 / 32 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A9 | events | 0 / 50 | not stated; safety; hypoglycaemia; registry:adverse_events |
Systolic blood pressure change (13 lines; O05)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | -5.8 mmHg | -9.1 to -2.6 | 54 | hypothetical; modified itt; R0004295:Supplement Table 1 | |
| 26 | A2 | change | -8.2 mmHg | -11.6 to -4.7 | 47 | hypothetical; modified itt; R0004295:Supplement Table 1 | |
| 26 | A2 vs A1 | md | -2.3 mmHg | -7.1 to 2.4 | hypothetical; modified itt; R0004295:Supplement Table 1 | ||
| 26 | A3 | change | -8.3 mmHg | -11.7 to -5.0 | 50 | hypothetical; modified itt; R0004295:Supplement Table 1 | |
| 26 | A3 vs A1 | md | -2.5 mmHg | -7.2 to 2.2 | hypothetical; modified itt; R0004295:Supplement Table 1 | ||
| 26 | A4 | change | -7.9 mmHg | -11.6 to -4.2 | 42 | hypothetical; modified itt; R0004295:Supplement Table 1 | |
| 26 | A4 vs A1 | md | -2.1 mmHg | -7.0 to 2.9 | hypothetical; modified itt; R0004295:Supplement Table 1 | ||
| 26 | A5 | change | -7.3 mmHg | -10.4 to -4.2 | 59 | hypothetical; modified itt; R0004295:Supplement Table 1 | |
| 26 | A5 vs A1 | md | -1.5 mmHg | -6.0 to 3.0 | hypothetical; modified itt; R0004295:Supplement Table 1 | ||
| 26 | A7 | change | -9.4 mmHg | -12.5 to -6.2 | 59 | hypothetical; modified itt; R0004295:Supplement Table 1 | |
| 26 | A7 vs A1 | md | -3.5 mmHg | -8.0 to 1.0 | hypothetical; modified itt; R0004295:Supplement Table 1 | ||
| 26 | A9 | change | -8.0 mmHg | -11.3 to -4.7 | 50 | hypothetical; modified itt; R0004295:Supplement Table 1 | |
| 26 | A9 vs A1 | md | -2.1 mmHg | -6.8 to 2.5 | hypothetical; modified itt; R0004295:Supplement Table 1 |
All cause mortality (9 lines; O20)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 55 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 0 / 51 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 56 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 47 | not stated; safety; registry:adverse_events | ||||
| A5 | events | 0 / 27 | not stated; safety; registry:adverse_events | ||||
| A6 | events | 0 / 34 | not stated; safety; registry:adverse_events | ||||
| A7 | events | 0 / 31 | not stated; safety; registry:adverse_events | ||||
| A8 | events | 0 / 32 | not stated; safety; registry:adverse_events | ||||
| A9 | events | 0 / 50 | not stated; safety; registry:adverse_events |
Serious adverse events (9 lines; O25)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 3 / 55 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 3 / 51 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 1 / 56 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 5 / 47 | not stated; safety; registry:adverse_events | ||||
| A5 | events | 1 / 27 | not stated; safety; registry:adverse_events | ||||
| A6 | events | 1 / 34 | not stated; safety; registry:adverse_events | ||||
| A7 | events | 0 / 31 | not stated; safety; registry:adverse_events | ||||
| A8 | events | 1 / 32 | not stated; safety; registry:adverse_events | ||||
| A9 | events | 1 / 50 | not stated; safety; registry:adverse_events |
Discontinuation due to adverse events (9 lines; O26)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 55 | not stated; randomized; registry:flow | ||||
| A2 | events | 1 / 51 | not stated; randomized; registry:flow | ||||
| A3 | events | 2 / 56 | not stated; randomized; registry:flow | ||||
| A4 | events | 0 / 47 | not stated; randomized; registry:flow | ||||
| A5 | events | 1 / 27 | not stated; randomized; registry:flow | ||||
| A6 | events | 0 / 34 | not stated; randomized; registry:flow | ||||
| A7 | events | 0 / 31 | not stated; randomized; registry:flow | ||||
| A8 | events | 0 / 32 | not stated; randomized; registry:flow | ||||
| A9 | events | 0 / 50 | not stated; randomized; registry:flow |
Nausea (9 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 3 / 55 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 12 / 51 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 21 / 56 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 16 / 47 | not stated; safety; registry:adverse_events | ||||
| A5 | events | 10 / 27 | not stated; safety; registry:adverse_events | ||||
| A6 | events | 9 / 34 | not stated; safety; registry:adverse_events | ||||
| A7 | events | 9 / 31 | not stated; safety; registry:adverse_events | ||||
| A8 | events | 8 / 32 | not stated; safety; registry:adverse_events | ||||
| A9 | events | 9 / 50 | not stated; safety; registry:adverse_events |
Vomiting (9 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 55 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 3 / 51 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 12 / 56 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 13 / 47 | not stated; safety; registry:adverse_events | ||||
| A5 | events | 9 / 27 | not stated; safety; registry:adverse_events | ||||
| A6 | events | 7 / 34 | not stated; safety; registry:adverse_events | ||||
| A7 | events | 11 / 31 | not stated; safety; registry:adverse_events | ||||
| A8 | events | 7 / 32 | not stated; safety; registry:adverse_events | ||||
| A9 | events | 4 / 50 | not stated; safety; registry:adverse_events |
Diarrhea (9 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 4 / 55 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 11 / 51 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 9 / 56 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 7 / 47 | not stated; safety; registry:adverse_events | ||||
| A5 | events | 7 / 27 | not stated; safety; registry:adverse_events | ||||
| A6 | events | 2 / 34 | not stated; safety; registry:adverse_events | ||||
| A7 | events | 9 / 31 | not stated; safety; registry:adverse_events | ||||
| A8 | events | 9 / 32 | not stated; safety; registry:adverse_events | ||||
| A9 | events | 6 / 50 | not stated; safety; registry:adverse_events |
Constipation (9 lines; O27D)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 55 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 7 / 51 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 7 / 56 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 6 / 47 | not stated; safety; registry:adverse_events | ||||
| A5 | events | 6 / 27 | not stated; safety; registry:adverse_events | ||||
| A6 | events | 1 / 34 | not stated; safety; registry:adverse_events | ||||
| A7 | events | 1 / 31 | not stated; safety; registry:adverse_events | ||||
| A8 | events | 4 / 32 | not stated; safety; registry:adverse_events | ||||
| A9 | events | 0 / 50 | not stated; safety; registry:adverse_events |
Acute pancreatitis (9 lines; O29)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 55 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A2 | events | 0 / 51 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A3 | events | 0 / 56 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A4 | events | 1 / 47 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A5 | events | 0 / 27 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A6 | events | 0 / 34 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A7 | events | 0 / 31 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A8 | events | 0 / 32 | not stated; safety; pancreatitis acute; registry:adverse_events | ||||
| A9 | events | 0 / 50 | not stated; safety; pancreatitis acute; registry:adverse_events |