Managing post-bariatric hypoglycemia: a systematic review of pharmacological therapies

Post-bariatric hypoglycemia (PBH) is a challenging and increasingly recognized complication following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). Multiple pharmacologic interventions have been explored for managing PBH, but evidence is scattered. This study aimed to systematically synthesize the evidence from comparative studies, single-intervention trials, case reports, and registered clinical trials to evaluate the efficacy of drug therapies for PBH.

This systematic review and mixed treatment comparison meta-analysis was conducted in accordance with PRISMA guidelines and registered on Open Science Framework. Databases searched included MEDLINE, Cochrane CENTRAL, and Google Scholar, with no language or year restrictions. Eligible studies included randomized clinical trials (RCTs), observational studies, single-drug evaluations, and case reports addressing pharmacologic treatments for PBH. Risk of bias was assessed using Cochrane and Joanna Briggs Institute tools. Mixed treatment comparisons were conducted with relative risk (RR) as effect estimates, and evidence quality was assessed with the GRADE approach.

Out of 2134 records screened, 13 comparative studies, five single-intervention studies, and 15 case reports were included. Among comparative studies, 12 were RCTs and one was a retrospective study. Meta-analysis revealed that anakinra and empagliflozin significantly reduced the risk of hypoglycemia compared to placebo (RR: 0.29; 95% CI: 0.09-0.91 for both). Dasiglucagon showed efficacy as a rescue agent. In single-intervention studies, pasireotide and acarbose prevented hypoglycemia in all patients. Case reports suggested variable success with agents such as liraglutide, verapamil, and semaglutide. However, the certainty of evidence was rated very low, with small sample sizes, heterogeneous definitions of PBH, and imprecise effect estimates limiting the robustness of conclusions.

Pharmacologic management of PBH shows promise with agents such as anakinra, empagliflozin, pasireotide, and acarbose. However, given the considerable heterogeneity, small sample sizes, and wide confidence intervals, very low quality of effect estimates, and varied definitions of PBH, these pooled estimates should be considered hypothesis-generating only, and not confirmatory. There is an urgent need for standardized PBH definitions, patient-centered outcome measures, longer follow-up, and adequately powered RCTs to establish evidence-based therapeutic guidelines.