Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1).

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.

• Authors: Carol Wysham, Thomas Blevins, Richard Arakaki, Gildred Colon, Pedro Garcia, Charles Atisso, Debra Kuhstoss, Mark Lakshmanan
• Journal: Diabetes care (Diabetes Care) Vol. 37 Issue 8 Pg. 2159-67 (Aug 2014) ISSN: 1935-5548 [Electronic] United States
• PMID: 24879836 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Immunoglobulin Fc Fragments
• Peptides
• Recombinant Fusion Proteins
• Thiazolidinediones
• Venoms
• Glucagon-Like Peptides
• Metformin
• Exenatide
• dulaglutide
• Pioglitazone

Topics

• Aged
• Blood Glucose (drug effects)
• Diabetes Mellitus, Type 2 (drug therapy)
• Drug Administration Schedule
• Drug Therapy, Combination
• Exenatide
• Female
• Glucagon-Like Peptides (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Hypoglycemia (drug therapy)
• Hypoglycemic Agents (administration & dosage, adverse effects)
• Immunoglobulin Fc Fragments (administration & dosage, adverse effects)
• Male
• Metformin (administration & dosage, adverse effects)
• Middle Aged
• Peptides (administration & dosage, adverse effects)
• Pioglitazone
• Recombinant Fusion Proteins (administration & dosage, adverse effects)
• Thiazolidinediones (administration & dosage, adverse effects)
• Venoms (administration & dosage, adverse effects)