Carol Wysham1, Thomas Blevins2, Richard Arakaki3, Gildred Colon4, Pedro Garcia5, Charles Atisso6, Debra Kuhstoss6, Mark Lakshmanan7. 1. Redwood Clinic, Spokane, WA. 2. Texas Diabetes and Endocrinology, Austin, TX. 3. University of Hawaii at Manoa, Honolulu, HI. 4. American Telemedicine Center of Puerto Rico, San Juan, PR. 5. University Hospital Autonomous University of Nuevo León, Monterrey, Mexico. 6. Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN. 7. Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN lakshmanan_mark@lilly.com.
Abstract
OBJECTIVE: To compare the efficacy and safety of dulaglutide, a once-weekly GLP-1 receptor agonist, with placebo and exenatide in type 2 diabetic patients. The primary objective was to determine superiority of dulaglutide 1.5 mg versus placebo in HbA1c change at 26 weeks. RESEARCH DESIGN AND METHODS: This 52-week, multicenter, parallel-arm study (primary end point: 26 weeks) randomized patients (2:2:2:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, exenatide 10 μg, or placebo (placebo-controlled period: 26 weeks). Patients were treated with metformin (1,500-3,000 mg) and pioglitazone (30-45 mg). Mean baseline HbA1c was 8.1% (65 mmol/mol). RESULTS: Least squares mean ± SE HbA1c change from baseline to the primary end point was -1.51 ± 0.06% (-16.5 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, -1.30 ± 0.06% (-14.2 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, -0.99 ± 0.06% (-10.8 ± 0.7 mmol/mol) for exenatide, and -0.46 ± 0.08% (-5.0 ± 0.9 mmol/mol) for placebo. Both dulaglutide doses were superior to placebo at 26 weeks (both adjusted one-sided P < 0.001) and exenatide at 26 and 52 weeks (both adjusted one-sided P < 0.001). Greater percentages of patients reached HbA1c targets with dulaglutide 1.5 mg and 0.75 mg than with placebo and exenatide (all P < 0.001). At 26 and 52 weeks, total hypoglycemia incidence was lower in patients receiving dulaglutide 1.5 mg than in those receiving exenatide; no dulaglutide-treated patients reported severe hypoglycemia. The most common gastrointestinal adverse events for dulaglutide were nausea, vomiting, and diarrhea. Events were mostly mild to moderate and transient. CONCLUSIONS: Both once-weekly dulaglutide doses demonstrated superior glycemic control versus placebo and exenatide with an acceptable tolerability and safety profile.
RCT Entities:
OBJECTIVE: To compare the efficacy and safety of dulaglutide, a once-weekly GLP-1 receptor agonist, with placebo and exenatide in type 2 diabeticpatients. The primary objective was to determine superiority of dulaglutide 1.5 mg versus placebo in HbA1c change at 26 weeks. RESEARCH DESIGN AND METHODS: This 52-week, multicenter, parallel-arm study (primary end point: 26 weeks) randomized patients (2:2:2:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, exenatide 10 μg, or placebo (placebo-controlled period: 26 weeks). Patients were treated with metformin (1,500-3,000 mg) and pioglitazone (30-45 mg). Mean baseline HbA1c was 8.1% (65 mmol/mol). RESULTS: Least squares mean ± SE HbA1c change from baseline to the primary end point was -1.51 ± 0.06% (-16.5 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, -1.30 ± 0.06% (-14.2 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, -0.99 ± 0.06% (-10.8 ± 0.7 mmol/mol) for exenatide, and -0.46 ± 0.08% (-5.0 ± 0.9 mmol/mol) for placebo. Both dulaglutide doses were superior to placebo at 26 weeks (both adjusted one-sided P < 0.001) and exenatide at 26 and 52 weeks (both adjusted one-sided P < 0.001). Greater percentages of patients reached HbA1c targets with dulaglutide 1.5 mg and 0.75 mg than with placebo and exenatide (all P < 0.001). At 26 and 52 weeks, total hypoglycemia incidence was lower in patients receiving dulaglutide 1.5 mg than in those receiving exenatide; no dulaglutide-treated patients reported severe hypoglycemia. The most common gastrointestinal adverse events for dulaglutide were nausea, vomiting, and diarrhea. Events were mostly mild to moderate and transient. CONCLUSIONS: Both once-weekly dulaglutide doses demonstrated superior glycemic control versus placebo and exenatide with an acceptable tolerability and safety profile.
Authors: Tito Borner; Jayme L Workinger; Ian C Tinsley; Samantha M Fortin; Lauren M Stein; Oleg G Chepurny; George G Holz; Aleksandra J Wierzba; Dorota Gryko; Ebba Nexø; Evan D Shaulson; Ankur Bamezai; Valentina A Rodriguez Da Silva; Bart C De Jonghe; Matthew R Hayes; Robert P Doyle Journal: Cell Rep Date: 2020-06-16 Impact factor: 9.423