Treatment-duration-wise harm profile of insulin-sodium-glucose co-transporter inhibitor co-treatment in type 1 diabetes mellitus patients.

Abstract

The treatment duration of insulin-sodium-glucose co-transporter inhibitors (SGLTis) co-treatment of type 1 diabetes mellitus (T1DM) patients in randomized controlled trials (RCTs) varies by 1-52weeks. Henceforth, treatment duration-wise, we compared the following insulin-treatment adjuncts- mega- versus low-dose SGLTis, SGLTis versus placebo, and different SGLTi dosages. Double-blinded RCTs reporting the above were searched (using terms like insulin-dependent, "juvenile-onset diabetes," and "sodium glucose cotransport*") in the PubMed, Embase, and Scopus databases and appraised using a Cochrane tool. The risks across different SGLTi-dosages were compared using network meta-analysis. Random-effect pairwise meta-analysis was performed for the remaining harm juxtapositions. Meta-analyses were performed for the following treatment durations- < 4weeks, 4 to < 24weeks, and ≥ 24weeks. For meta-analysis and certainty of evidence assessment, we used the Stata statistical software and the GRADE method, respectively. A total of 15 (low risks of bias) studies sourcing data from about 7,330 T1DM patients were reviewed. Meta-analysis findings of ≥ 24weeks long trials were- a. SGLTi-insulin co-treatment increased the genital infection (GI) (RR: 3.51; 95% CI: 2.59, 4.77), diabetic ketoacidosis (DKA) and (RR: 3.25; 95% CI:1.29, 8.16), and serious side effects (RR: 1.43; 95% CI: 1.05, 1.94) risk. b. SGLT2i-insulin increased the GI risk (RR: 3.77; 95% CI: 2.31, 6.16; high-quality evidence). c. Sotagliflozin-insulin increased the GI (RR: 3.36; 95% CI: 2.28, 4.96) and DKA (RR: 6.69; 95% CI: 2.75, 16.32) risk (both high-quality evidence). Compared to low-dose, megadose SGLTi treatment for 4 to < 24weeks increased the GI risk. The remaining analyses were not statistically significantly different. On moderate to long-term treatment (24-52weeks) of T1DM patients, insulin-SGLT2i co-treatment was associated with GI risk, and insulin-sotagliflozin co-treatment was associated with DKA and GI risk. The online version contains supplementary material available at 10.1007/s40200-023-01192-7.