Alteration in fasting glucose after prolonged treatment with a thiazide diuretic

Aims: Thiazide diuretics are recommended as first line antihypertensive treatment, but may contribute to new onset diabetes. We aimed to describe change in fasting glucose (FG) during prolonged thiazide treatment in an observational setting. Methods: We conducted an observational, non-randomized, open label, follow-up study of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 studies. We enrolled previous participants from the PEAR or PEAR-2 studies with at least 6 months of continuous treatment with either hydrochlorothiazide (HCTZ) or chlorthalidone. Linear regression was used to identify associations with changes in FG after prolonged thiazide and thiazide-like diuretic treatment. Results: A total of 40 participants were included with a mean 29 (range 8-72) months of thiazide treatment. FG increased 6.5 (SD 13.0) mg/dL during short-term thiazide treatment and 3.6 (SD 15.3) mg/dL FG during prolonged thiazide treatment. Increased FG at follow-up was associated with longer thiazide treatment duration (β=0.34, p=0.008) and lower baseline FG (β=-0.46, p=0.02). β blocker treatment in combination with prolonged thiazide diuretic treatment was also associated with increased FG and increased 2-h glucose obtained from OGTT. Conclusions: Our results indicate that prolonged thiazide treatment duration is associated with increased FG and that overall glycemic status worsens when thiazide/thiazide-like diuretics are combined with β blockers.