The analyses included six pivotal randomized, double-blind trials of dulaglutide 1.5 mg in participants with T2D that measured sitting SBP and DBP from vital sign data around the timeline of 6 months (week 24 to week 26). Five placebo-controlled studies were used to estimate the effects between dulaglutide 1.5 mg and placebo. AWARD-1 (NCT01064687), AWARD-5 (NCT00734474), AWARD-8 (NCT01769378), and AWARD-10 (NCT02597049) were phase 3, placebo-controlled trials which investigated the safety and glycemic efficacy of dulaglutide with various background glycemic therapies (Table 1 ). Ferdinand et al. (NCT01149421) was a phase 2, randomized, double-blind, placebo-controlled trial which evaluated BP and heart rate effects of dulaglutide vs. placebo in participants with T2D with and without hypertension and BP < 140/90 mmHg. In addition, AWARD-11 (NCT03495102) was a phase 3, non-placebo-controlled trial to evaluate safety and glycemic efficacy of dulaglutide 3.0 mg and 4.5 mg to dulaglutide 1.5 mg.
Study design for placebo-controlled trials included in the meta-analysis
| Parameters | AWARD-1 | AWARD-5 | AWARD-8 | AWARD-10 | AWARD-11 | Ferdinand et al |
|---|---|---|---|---|---|---|
| Phase | Phase III | Phase II/III | Phase III | Phase III | Phase III | Phase II |
| Randomization | Randomized | Randomized | Randomized | Randomized | Randomized | Randomized |
| Blinding | Blinding | Double-blind | Double-blind | Double-blind | Double-blind | Double-blind |
| Primary Endpoint | A1c | A1c | A1c | A1c | A1c | 24-h SBP |
| Study Treatment Period | 52 weeks | 24 months | 24 weeks | 24 weeks | 52 weeks | 26 weeks |
| Last scheduled visit with PBO | 26 weeks | 6 months | 24 weeks | 24 weeks | 52 weeks (no PBO) | 26 weeks |
| Background therapy (Add-ons) | Met + TZD | Met mono | SU mono | SGLT2i with or without metformin | Met mono | Stable OAM |
| Key inclusion/ exclusion criteria | ||||||
| Age | ≥ 18 years | 18–75 years | ≥ 18 years | ≥ 18 years | ≥ 18 years | ≥ 18 years |
| T2D duration | NA | ≥ 6 months | NA | NA | for ≥ 6 months | NA |
| A1c | 7.0–11.0 | 7.0–9.5 | 7.5–9.5 | 7.0–9.5 | 7.5–11 | 7–9.5 |
| BMI | 23–45 | 25–40 | ≤ 45 | ≤ 45 | ≥ 25 | NA |
| Medication | Stable OAM | Diet & exercise / metformin and/or other OAM | Stable SU | SGLT2i with or without metformin for ≥ 3 months | Stable metformin for ≥ 3 months | OAM |
BMI body mass index, NA not applicable for the study’s design, Met metformin, mono monotherapy, OAM oral antihyperglycemic medication, PBO placebo, SBP systolic blood pressure, SGLT2i sodium-glucose cotransporter-2 inhibitors, SU sulfonylurea, T2D type 2 diabetes, TZD thiazolidinediones
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