Initiation of sulfonylureas versus metformin is associated with higher blood pressure at one year

Abstract

Purpose: To determine if incident oral antidiabetic drug (OAD) use was associated with 12-month systolic blood pressure (BP) and if this was mediated through body mass index (BMI) changes.

Methods: A retrospective cohort of veterans with hypertension who initiated metformin (n = 2057) or sulfonylurea (n = 1494) between 1 January 2000 and 31 December 2007 in the Veterans Administration Mid-South Network was assembled. Patients were included if they had complete covariates, including 12-month BP and BMI, and persisted on therapy for 12 months. Linear regression was conducted to investigate the effect of OADs on 12-month systolic BP adjusting for demographics, glycated hemoglobin, creatinine, BMI, health care utilization, and comorbidities, including cardiovascular disease (CVD). A second analysis examined if these effects were mediated by BMI change. The secondary outcome was the proportion of patients who had a controlled BP (≤ 140/90 mmHg) at 12 months adjusted for baseline BP and covariates.

Results: Patients were white (82%) males (97%) with median age of 64 years (interquartile range [IQR] 57, 72), and 27% had history of CVD. Sulfonylurea users had a 1.33 mmHg (0.16, 2.50, p = 0.03) higher 12-month systolic BP than metformin users. The median change in BMI from OAD initiation to 12 months was -0.76 (IQR -1.78, 0.07) and 0.21 (IQR -0.57, 1.03) among metformin and sulfonylurea users, respectively. In a model adjusting for BMI change, the difference in 12-month systolic BP between sulfonylurea and metformin users became insignificant (0.23 (-1.00, 1.45), p = 0.72), while one BMI unit change was associated with an increase in 12-month systolic BP of 1.07 mmHg (0.74, 1.40, p < 0.0001). At 12 months, 68.3% of metformin patients had controlled BP versus 64.2% of sulfonylurea patients (p = 0.01).

Conclusions: Compared with metformin, sulfonylurea initiation was associated with increased systolic BP at 12 months, which appears to be mediated by the differential effects of these drugs on BMI.