Thiazide Diuretic–Induced Change in Fasting Plasma Glucose: a Meta-analysis of Randomized Clinical Trials

Background Prior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure’s definition has changed over time. Aim To determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics. Data Sources A research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014). Study Selection Randomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling < 50 participants, those with a follow-up period of < 4 weeks, and conference abstracts were excluded. Data Extraction Independent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted. Data Synthesis Ninety-five studies were included ( N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20 mmol/L (95% CI 0.15–0.25); I 2 = 84%) (1 mmol/L = 18 mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent. Conclusion Thiazide diuretics have a small and clinically unimportant impact on FPG.