Should Certain Antihyperglycemic Medications Be Preferred Over Antihypertensive Medications for Blood Pressure Control in Special Populations With Diabetes Mellitus?
Authors: Kenneth A. Jamerson
Journal: Circulation (2019)

ypertension affects approximately two-thirds of patients with diabetes mellitus (DM).Moreover, it synergistically increases cardiovascular morbidity and mortality.It is interesting to note that there is evidence to suggest that controlling blood pressure (BP) will reduce more cardiovascular disease (CVD) events than glycemic control alone. 1,2The ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) assessed the effects of optimal glycemic and BP targets, and lipid management in 10 000 patients with DM.Only the randomized comparison of BP management (and not the glycemic or lipid arms) demonstrated cardiovascular benefit. 3A newer class of DM medication, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, specifically, empagliflozin (EMPA), has been shown to reduce cardiovascular outcomes, and is currently undergoing randomized trial evaluation in patients with chronic heart failure and chronic kidney disease.In this issue of Circulation, there are 2 reports on the BP-lowering effects of EMPA in 2 very different special populations (patients at greater risk for CVD who may derive unique benefit from the mechanism of BP reduction associated with EMPA).Both reports converge to suggest that EMPA produces reductions in BP of sufficient magnitude to confer reduction in cardiovascular morbidity and mortality.In this issue, Ferdinand et al 4 demonstrate that 25 mg of EMPA reduces 24hour mean systolic blood pressure (SBP) by 8.5 mm Hg (placebo corrected).The confidence interval suggested an effect as large as 13.7 mm Hg and a minimum effect of 3 mm Hg.However, because glycemic control was the primary end point of the study, the robustness of the BP results was not fully examined because the sensitivity analyses were limited to the primary aim.About 10% of the randomly assigned patients were not included in the efficacy analysis.The effects of missing data are smoothed out by carrying forward the last observed data point.Despite the limitations, the authors were able to reveal reductions in BP in 72 blacks with DM.Ferdinand et al reported a high drug adherence rate of >92%, suggesting that EMPA was a highly acceptable add-on therapy.Study participants were concomitantly being treated with antihypertensive medication; moreover, one-third would be considered treatment-resistant patients (on ≥3 antihypertensive medications).In the PATHWAY-2 trial (Optimum Treatment for Drug-Resistant Hypertension), Williams et al 5 found spironolactone to be superior to either a β-or α-blocker as a fourth-line add-on agent in the treatment of resistant hypertension, reporting a mean reduction of 8.7 mm Hg in home SBP.The results of Ferdinand et al should compel a follow-up study in patients with treatment-resistant hypertension.To date, clinicians seeking an antihypertensive agent to use as a fourth-line add-on drug to existing medications in patients with DM would be challenged to identify a drug with either the efficacy or tolerability demonstrated with EMPA in this report.