Dulaglutide 1.5 mg once weekly lowered HbA1c by up to 1.5% — outperforming exenatide, sitagliptin, and insulin glargine, and matching liraglutide — with weight loss benefits and infrequent hypoglycemia.
-1.5% HbA1cDulaglutide 1.5 mg achieved the largest HbA1c reduction at 26 weeks, outperforming exenatide (-0.99%), sitagliptin (-0.6%), and insulin glargine (-0.63%)
What the researchers found
Across four AWARD randomized controlled trials with follow-up ranging from 26 to 104 weeks, dulaglutide demonstrated superior or noninferior glycemic control compared to all tested comparators:
• vs exenatide 10 µg twice daily: HbA1c reduction of -1.5% (1.5 mg) and -1.3% (0.75 mg) vs -0.99%
• vs sitagliptin 100 mg daily: -1.22% (1.5 mg) and -1.01% (0.75 mg) vs -0.6%
• vs insulin glargine: -1.08% (1.5 mg) vs -0.63% (significant); -0.76% (0.75 mg) vs -0.63% (not significant)
• vs liraglutide 1.8 mg daily: dulaglutide 1.5 mg was noninferior
More dulaglutide patients achieved HbA1c targets of <7% and ≤6.5%. Weight reduction was greater with dulaglutide than sitagliptin and exenatide. Hypoglycemia was infrequent across all dulaglutide groups.
Why it matters
GLP-1 receptor agonists have transformed type 2 diabetes treatment, and dulaglutide's once-weekly dosing offers a major convenience advantage. This systematic review provided early comprehensive evidence that dulaglutide was not just convenient but also more effective than several established treatments, supporting its adoption as a frontline option for patients struggling with blood sugar control.
How the study worked
Systematic review searching MEDLINE, MEDLINE In-Process, EMBASE, and conference abstracts from 2005 to January 2015. FDA and EMA websites and company data were also searched. Four manufacturer-funded randomized controlled trials from the AWARD program were included, comparing dulaglutide (0.75 mg and 1.5 mg once weekly) against exenatide, insulin glargine, sitagliptin, liraglutide, and placebo. The primary outcome was change in HbA1c.
What this study cannot tell us
All four included trials were manufacturer-funded, introducing potential bias. The review notes that long-term safety data were still needed at the time of publication. Only dual and triple therapy combinations were assessed. The comparator doses and regimens varied across trials, making direct cross-trial comparisons imprecise. The search ended in early 2015, so subsequent AWARD trials and real-world evidence are not included.
How to read the evidence
This is a systematic review of four randomized controlled trials, which represents a high level of evidence. However, all included trials were manufacturer-funded, and the review notes limitations in long-term safety data. The rigorous search methodology and inclusion of multiple RCTs strengthen the overall evidence quality.
When this study was published
Published in 2015, this review covered the initial AWARD trial program. Since then, dulaglutide has accumulated extensive real-world data, cardiovascular outcome trial results (REWIND), and has been joined by newer GLP-1 agonists with even larger effect sizes.
The bigger picture
This review captured dulaglutide at the moment of its clinical establishment, synthesizing the AWARD trial program that led to regulatory approval. The GLP-1 agonist class has since expanded enormously, with drugs like semaglutide gaining prominence for both diabetes and obesity. Dulaglutide's strong AWARD data helped validate the entire class and paved the way for next-generation peptide therapeutics.
Questions still open
- How does dulaglutide's long-term cardiovascular safety compare to other GLP-1 agonists like semaglutide and liraglutide?
- Do the HbA1c advantages seen at 26 weeks persist over years of treatment in real-world practice?
- How does dulaglutide compare to newer, higher-dose GLP-1 agonists that have since entered the market?
Common questions
How does dulaglutide compare to daily diabetes injections?
What are the main side effects of dulaglutide?
Read the original research
A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide.
Diabetes, metabolic syndrome and obesity : targets and therapy, 8, 363-86
Citation
Gurung, Tara; Shyangdan, Deepson S; O'Hare, Joseph Paul; Waugh, Norman. (2015). A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide.. Diabetes, metabolic syndrome and obesity : targets and therapy, 8, 363-86. https://doi.org/10.2147/DMSO.S34418