PURPOSE: Verapamil, an L-type calcium channel blocker treating hypertension, arrhythmia, and other cardiovascular diseases, has emerged as a potential drug for lowering blood glucose by regulating cellular calcium homeostasis and affecting expression of apoptosis-related proteins in pancreatic β-cells. However, this promising effect must be weighed against potential risks, including cardiovascular adverse effects of this drug. METHODS: We conducted a systematic review and meta-analysis and included randomized controlled trials (RCTs) assessing verapamil in individuals with type 1 or type 2 diabetes. The primary outcomes were glycated hemoglobin (HbA1c) and serum glucose concentration. The secondary outcomes were area under the curve (AUC) values for C-peptide level, body weight, changes in HbA1c and blood glucose concentration pre- and post-intervention, and adverse drug reactions. RESULTS: A total of eight RCTs involving 1100 patients were included in the analysis. Meta-analysis showed that verapamil effectively lowered blood glucose levels (weighted mean difference [WMD] -6.38, 95% CI -12.52, -0.25 mg/dL, P = 0.04
6 trials), decreased HbA1c (WMD -0.45, 95% CI -0.66, -0.23%, P <
0.001
7 trials), and increased C-peptide AUC (WMD 0.27, 95% CI 0.21, 0.32 pmol/mL, P <
0.0001
2 trials) in patients with both type 1 and type 2 diabetes, without significant trial-related adverse events (OR 1.33, 95% CI 0.85, 2.09, P = 0.21). CONCLUSION: The adjunctive use of verapamil to standard hypoglycemic therapy is a safe and effective means of improving glycemic control in diabetic patients. However, the limited scale of RCTs and heterogeneity of basic glucose-lowering regimens across studies might constrain generalizability of these findings. Future high-quality research is warranted to further elucidate the role of verapamil in diabetes management.