Medication Adherence to SGLT2 Inhibitors vs. Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: A Meta-Analysis

Background: Glycemic control with antihyperglycemics in individuals with diabetes has long been associated with reductions in the incidence of chronic kidney disease (CKD). Recent evidence has also demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2Is) slow the progression of CKD. However, optimal medication adherence with antihyperglycemics is needed to achieve outcomes. We sought to perform a meta-analysis to compare medication adherence to SGLT2Is versus glucagon-like peptide-1 receptor agonists (GLP-1RAs). Methods: A systematic search of Medline and Embase was conducted through October 2023. To meet inclusion criteria, articles had to be published in the full text form and directly compare medication adherence to SGLT2Is versus GLP-1RAs. Only studies evaluating real-world data and utilizing proportion of days covered (PDC) to measure adherence were included. Non-adherence, defined as the proportion of patients with a PDC<80%, was the primary outcome for this study. A subgroup analysis evaluating results among studies conducted in the US was performed. Results: We identified 8 studies evaluating 205,103 patients for inclusion. Most studies derived data from the US (n= 5 studies). The proportion of patients with non-adherence (i.e., a PDC<80%) ranged from 27%-62% among those taking SGLT2Is and 26%-80% among those taking GLP1-RAs across included studies. Upon meta-analysis, SGLT2I use was associated with a numerically lower risk of non-adherence compared to GLP-1RA use but no statistical difference was observed (relative risk [RR] = 0.86; 95% confidence interval [CI] 0.72-1.02). In the analysis including only US studies, SGLT2I use was associated with a 23% lower risk of non-adherence compared to GLP-1RA use (RR = 0.77; 95% CI 0.72-0.82). Conclusion: In this meta-analysis of 8 studies that included ~200,000 patients, SGLT2I use was associated with numerically higher medication adherence vs. GLP-1RA use; however, this difference was not statistically significant in the overall analysis. SGLT2I use was associated with significantly higher adherence when the analysis was limited to US studies. Adherence may differ across antihyperglycemic regimens and thus impact outcomes achieved with these regimens.