Effects of Glucose‐Lowering Medications on Intrapancreatic Fat Deposition: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

BACKGROUND: The pancreas is a key metabolic organ, and excessive intrapancreatic fat deposition (IPFD) has been implicated in the pathogenesis of Type 2 diabetes. Although IPFD is believed to be reversible, it remains unclear whether glucose-lowering medications can reduce it. This study aimed to perform a field-wide systematic review of randomized controlled trials (RCTs) investigating the effects of such medications on IPFD. METHODS: Three electronic databases-MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials-were searched. RCTs comparing the effects of pharmacological interventions with standard care or placebo on IPFD were meta-analyzed using a random-effects model. The mean difference in IPFD, with its corresponding 95% confidence interval, served as the primary effect estimate. RESULTS: Eight RCTs met the eligibility criteria, five of which were placebo-controlled. In the overall analysis, glucose-lowering medications were associated with a significant reduction in IPFD (mean difference = -1.5; 95% CI: -1.8, -1.1; p < 0.001). Constraining the analysis to placebo-controlled RCTs yielded a larger effect size (mean difference = -1.8; 95% CI: -3.1, -0.5; p = 0.01). Among the medication classes meta-analyzed, significant reductions in IPFD were observed with GLP-1 receptor agonists (mean difference = -1.6; 95% CI: -2.5, -0.7; p = 0.01) and SGLT-2 inhibitors (mean difference = -1.4; 95% CI: -1.6, -1.1; p = 0.002). CONCLUSION: Glucose-lowering medications have the potential to reduce IPFD. Rigorously designed RCTs are warranted to confirm the responsiveness of IPFD to pharmacological interventions and to guide their clinical application.