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How Once-Weekly Dulaglutide Stacks Up for Type 2 Diabetes: Efficacy and Safety Review

evidence
The takeaway

Dulaglutide, a once-weekly GLP-1 receptor agonist, consistently outperformed several standard diabetes medications in lowering A1c with a manageable side effect profile.

Up to -1.64% A1c reduction

Dulaglutide's maximum A1c-lowering effect observed across head-to-head clinical trials over 52-104 weeks of treatment.

What the researchers found

Dulaglutide demonstrated robust A1c reduction ranging from -0.78% to -1.64% over 52-104 weeks in head-to-head comparisons, consistently outperforming metformin, insulin glargine, and sitagliptin. As add-on therapy, it provided additional A1c lowering of -1.4% to -1.44% beyond monotherapy with glimepiride or glargine.

Dulaglutide also outperformed exenatide when added to metformin plus pioglitazone, and beat glargine when added to metformin plus glimepiride. It was non-inferior to liraglutide when added to metformin. In nearly all AWARD trials, full-dose dulaglutide enabled significantly more patients to reach their A1c goals. Pooled safety data showed no increased risk of pancreatitis or neoplasm.

Why it matters

GLP-1 receptor agonists have transformed type 2 diabetes management. This review provided a comprehensive snapshot of dulaglutide's clinical performance at a time when the class was rapidly expanding, helping clinicians understand how this once-weekly option compared to daily alternatives and other diabetes medications in real trial settings.

How the study worked

This was a review of published clinical trial data, primarily from the AWARD (Assessment of Weekly AdministRation of LY2189265 in Diabetes) series of trials. The review synthesized results from head-to-head comparisons against multiple standard-of-care agents and examined class-wide meta-analyses for side effect profiles.

What this study cannot tell us

This is a narrative review, not a systematic review or meta-analysis, so it may not capture all available data. The REWIND cardiovascular outcomes trial had not yet reported at the time of publication. Head-to-head comparisons across different trials are limited by differing patient populations, baseline characteristics, and study designs. Long-term safety data beyond the trial periods reviewed was limited.

How to read the evidence

This is a narrative review summarizing data from multiple randomized controlled trials (the AWARD series). While the underlying trials provide strong evidence, the review itself does not apply systematic methodology or conduct independent statistical analysis.

When this study was published

Published in 2018, this review predates the REWIND cardiovascular outcomes trial results and the newer wave of GLP-1 agonists. The efficacy data remains valid, but the clinical landscape for GLP-1 therapies has evolved significantly since.

The bigger picture

GLP-1 receptor agonists like dulaglutide represent a major class of peptide-based therapeutics that have reshaped diabetes care. The convenience of once-weekly dosing has been a significant advantage for patient adherence. Since this review was published, the REWIND trial confirmed cardiovascular benefits for dulaglutide, and the entire GLP-1 class has expanded dramatically with agents like semaglutide gaining prominence for both diabetes and weight management.

Questions still open

  • Would dulaglutide demonstrate cardiovascular risk reduction comparable to liraglutide in the upcoming REWIND trial?
  • How does dulaglutide's real-world adherence and effectiveness compare to its performance in controlled clinical trials?
  • Could higher doses of dulaglutide achieve even greater A1c reductions while maintaining an acceptable safety profile?

Common questions

How does dulaglutide compare to other once-weekly GLP-1 drugs?
At the time of this review, dulaglutide outperformed exenatide once weekly and was non-inferior to the daily GLP-1 agonist liraglutide. It consistently helped more patients reach A1c targets compared to most comparators in the AWARD trial series.
What are the most common side effects of dulaglutide?
The most common side effects are gastrointestinal: nausea, vomiting, and diarrhea. Meta-analyses suggest nausea and vomiting are less frequent with longer-acting agents like dulaglutide compared to shorter-acting GLP-1 drugs, though diarrhea may be somewhat more common. Pooled data showed no increased risk of pancreatitis or cancer.

Read the original research

Efficacy and safety profile of once-weekly dulaglutide in type 2 diabetes: a report on the emerging new data.

Diabetes, metabolic syndrome and obesity : targets and therapy, 11, 187-197

Citation

Kugler, Anne J; Thiman, Michael L. (2018). Efficacy and safety profile of once-weekly dulaglutide in type 2 diabetes: a report on the emerging new data.. Diabetes, metabolic syndrome and obesity : targets and therapy, 11, 187-197. https://doi.org/10.2147/DMSO.S134960