Gender Bias in Clinical Trials of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Type 2 Diabetes Mellitus: A Systematic Review.

Abstract

Aims: The study is aimed at assessing gender bias in Phase III clinical trials (CTs) of sodium-glucose cotransporter type 2 (iSGLT2) inhibitors in adults with Type 2 diabetes mellitus (T2DM). Methods: We searched PubMed and EMBASE databases until June 2023. To estimate sex bias in recruitment, the difference between F-Particip (fraction of women recruited) and F-Prev (prevalence fraction of women with T2DM) was calculated. A significant sex bias in recruitment was considered to exist when the difference between F-Particip and F-Prev was greater than 0.05, 0.1, and 0.2. The analysis was considered to have a sex bias when the efficacy variables were not analyzed by sex. Gender of the first, last, and corresponding author was also assessed. Results: In total, 70 articles met all inclusion criteria. Sex bias in recruitment showed variable results depending on the reference value. No significant sex bias in recruitment was found in the total number of included patients. Examining each CT individually, using values of significant sex bias in recruitment of ±0.05, ±0.1, or ±0.2, we found that 41.4%, 20%, and 5.7% of the trials, respectively, showed this bias. In 34.3% of the articles, women were the first, last, or corresponding authors. Sex-based analysis of the results was performed in five studies. Conclusions: Although the proportion of women included in iSGLT2 CTs seems acceptable, gender bias persists in the analysis of variables and in the study authors. However, the lack of gender focus may be explained by the characteristics of the patients included in the CTs.