Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review
Document Type
Article
Publication Date
12-1-2023
Abstract
Background: A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. Results: Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes. Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.
Recommended Citation
Young, K., McInnes, E., Massey, R., Kahkoska, A., Pilla, S., Raghavan, S., Stanislawski, M., Tobias, D., McGovern, A., McGovern, A., Dawed, A., Jones, A., Pearson, E., Pearson, E., Dennis, J., Dennis, J., Franks, P., Rich, S., Wagner, R., Vilsbøll, T., Vesco, K., Udler, M., Tuomi, T., Sweeting, A., Sims, E., Sherr, J., Semple, R., Reynolds, R., Redondo, M., Redman, L., Pratley, R., Pop-Busui, R., Pollin, T., & Perng, W. (2023). Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review. Retrieved from https://repository.lsu.edu/clinical_research_pubs/333