Certain sulfonylurea drugs increase serum free fatty acid in diabetic patients: A systematic review and meta-analysis

BACKGROUND: Sulfonylurea (SU) is a commonly used antidiabetic drugs effective for type 2 diabetes mellitus. Previous studies have reported that the SU treatment could alter the serum free fatty acid (FFA) concentration in diabetic patients; however, their exact effects remain unknown. AIM: To assess the impact of SU on the FFA level in diabetic patients. METHODS: A systematic literature search was conducted by consulting the PubMed, EMBASE, Cochrane Library, Reference Citation Analysis (https://www.referencecitationanalysis.com/), and Web of Science databases from January 1, 1991 to July 30, 2021. Either a fixed-effects model or random-effects model was applied to study the association between SU treatment and FFA concentration according to the heterogeneity test. Two investigators independently performed data extraction. The mean difference (MD) and corresponding 95% confidence interval (CI) were used to measure effect size. R3.5.1 software was utilized for conducting statistical analyses. RESULTS: A total of 13 studies with 2273 individuals were selected. Results indicated that FFA concentration increased slightly after treatment with SU (MD = 0.08, 95%CI: 0.03-0.12, P < 0.01). In addition, we found that SU treatment combined with other antidiabetics could also increase the concentration of serum FFA (MD = 0.14, 95%CI: 0.01-0.28, P < 0.01). Regarding the type of SU, there was no significant difference in FFA concentration with glimepiride or glibenclamide. FFA concentration was higher at ≥ 12 wk (MD = 0.09, 95%CI: 0.04-0.13) but not at < 12 wk (MD = 0.01, 95%CI: -0.07-0.09). CONCLUSION: SU treatment could increase the serum FFA concentration in diabetic patients. The fundamental underlying mechanism still needs further investigation.