Spironolactone and glucose metabolism, a systematic review and meta-analysis of randomized controlled trials

- Some drugs are effective for cardiovascular disease but increase diabetes risk.
- Spironolactone might worsen glycemic control, but the evidence is unclear.
- Spironolactone increasing HbA1c adds to the concern about adverse glycemic effects.
- The pleiotropic effects might provide insight into etiology of both diseases.

Diabetes predicts cardiovascular disease (CVD); some drugs are effective for CVD prevention but increase the risk of diabetes. In a systematic review and meta-analysis of placebo-controlled trials, we assessed if spironolactone, a mineralocorticoid receptor antagonist, affected glycemic control. We searched PubMed using (“spironolactone” or “aldactone”) and trial and (“glucose” or “diabetes” or “insulin” or “insulin resistance”) until January 4, 2016. In total, 18 eligible trials were identified; 10 on fasting glucose, 8 on hemoglobin A1c (HbA1c), 7 on homeostatic model assessment (HOMA)-insulin resistance (IR), and 8 on insulin. Spironolactone increased HbA1c (0.16%, 95% confidence interval 0.02 to 0.30) but had no clear effect on fasting glucose, HOMA-IR, and insulin. A mechanistic randomized controlled trial in people with and without diabetes might provide insight concerning these pleiotropic effects on diabetes and CVD relevant to prevention of both diseases.