Risk of heart failure in patients with type 2 diabetes receiving insulin therapy: a meta-analysis of observational studies

Abstract

Aim. To compare the effect of insulin therapy and oral hypoglycemic agents (OHAs) on the risk of heart failure (HF) in patients with type 2 diabetes (T2D) using different databases.Material and methods. The systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis included studies that compared the risk of HF in T2D patients, depending on the OHA therapy in the presence of a group of patients receiving insulin therapy. The inclusion criteria were a duration of treatment of at least two years with at least 1000 included patients. The analysis did not include studies that compared the types and regimens of insulin therapy without a control group (antidiabetic drugs), which included patients with acute complications of type 2 diabetes and unstable conditions associated with comorbidities, in which no clinical outcomes were reported. Search was conducted in August 2022 using several databases (PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) at the Cochrane Library, Elibrary) using the following keywords: heart failure development, 2 type diabetes mellitus, insulin.Results. Of the 1085 publications found in the search, 5 retrospective observational cohort clinical trials, including a total of 179777 patients with a mean duration of treatment of 67,2 months, met all criteria and were included in the analysis. Statistical analysis of the relative risk (RR) of HF in T2D patients receiving insulin therapy revealed a RR increase in all studies with a total RR using fixed effects model of 2,598 (95% confidence interval (CI), 2,346-2,878; p<0,001), while using the random effects model — 2,382 (95% CI, 1,565-3,626; p<0,001). When checking the statistical heterogeneity of the studies, a high heterogeneity was revealed (I2=93,8%).Conclusion. Meta-analysis of 5 retrospective observational studies including 179777 patients with T2D with a mean duration of treatment of 67,2 months showed that insulin therapy (without insulin glargine and degludec) in comparison with OHAs (without sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide type 1 receptor agonists) significantly increased the RR for HF using a fixed effects model by 2,6 times, while using the random effects model — by 2,4 times (p<0,001 for both).