Sodium-glucose cotransporter-2 inhibitors and gastrointestinal neoplasm risk in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
Abstract
Abstract Background The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. Materials and methods We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science to March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or another active comparator. The primary outcome was GI neoplasms; secondary, prespecified site-specific neoplasms (esophageal, gastric, hepatic, pancreatic, colorectal, rectal, biliary). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0, using fixed- or random-effects models according to the heterogeneity. Prespecified subgroups included agents, dose, exposure duration (≤ 52, 52–104, > 104 weeks), age, body mass index (BMI), and hemoglobin A1c (HbA1c). Publication bias was evaluated with funnel plots and Egger’s test. Results In a pooled analysis of 49 RCTs (n = 49,054), SGLT2 inhibitors therapy was not associated with the overall risk of GI neoplasm (OR = 1.10, 95% CI: 0.84–1.44; p = 0.46; I² = 0%). Site-specific analyses were likewise null for esophageal (OR = 1.12, 95% CI 0.37–3.45), gastric (1.20, 0.65–2.23), hepatic (0.62, 0.31–1.22), pancreatic (0.93, 0.52–1.66),…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 49,054 participants or records.
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