Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including dulaglutide, have been associated with elevations in pancreatic enzymes, yet the magnitude and clinical significance of these changes in overweight and obese patients with type 2 diabetes mellitus (T2DM) remain unclear. This systematic review and meta-analysis quantified the effects of subcutaneous dulaglutide on serum amylase and lipase concentrations in this population. PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to May 2026. Randomized controlled trials comparing dulaglutide with placebo in overweight or obese adults with T2DM and reporting amylase or lipase outcomes were included. Pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Seven study arms ( n = 2,570) contributed to the amylase analysis and 12 arms ( n = 3,041) to the lipase analysis. Dulaglutide significantly increased serum amylase (WMD: 3.85 U/L; 95% CI: 2.41–5.28; P < 0.001; I² = 74.1%) and lipase (WMD: 6.07 U/L; 95% CI: 3.87–8.26; P < 0.001; I² = 81.7%) compared with placebo. Subgroup analyses showed more pronounced elevations with shorter treatment durations (≤ 26 weeks) for both enzymes. Lipase increases were greater in patients with BMI ≥ 30 kg/m². Sensitivity analyses confirmed result stability, and no significant publication bias was detected. Dulaglutide produces small but statistically significant increases in serum amylase and lipase in overweight and obese patients with T2DM. These elevations remain well below clinically relevant thresholds for pancreatitis, supporting the overall pancreatic safety of dulaglutide, though monitoring is warranted in high-risk individuals.
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Dinislam et al. (2026) studied this question.
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