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

ABSTRACT 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.