Hemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin with renin–angiotensin system inhibitors in type 2 diabetic patients with albuminuria

OBJECTIVE: Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors is increasingly common. Pharmacological studies have suggested a potential adverse drug interaction between ACE inhibitors and DPP-4 inhibitors resulting in unfavorable hemodynamic changes; very few studies have examined such an interaction between angiotensin II receptor blockers (ARBs) and DPP-4 inhibitors. We investigated blood pressure (BP) and heart rate (HR) during treatment with the DPP-4 inhibitor linagliptin in individuals receiving either ACE inhibitors or ARBs in the MARLINA-T2D trial. METHODS: In this study, 360 individuals with type 2 diabetes and albuminuria receiving unchanged doses of ACE inhibitors or ARBs were randomized to linagliptin or placebo. Twenty-four-hour ambulatory BP monitoring, an exploratory endpoint, was conducted at baseline and after 24 weeks. RESULTS: Ambulatory BP monitoring data were available for 208 individuals (linagliptin: n = 111; placebo: n = 97). Baseline mean ± SD 24-h SBP and DBP were 132.5 ± 12.4 mmHg and 75.9 ± 9.4 mmHg, respectively; mean 24-h HR was 76.3 ± 10.1 bpm. At week 24, no overall effect of the DPP-4 inhibitor versus placebo was seen on mean 24-h SBP, DBP, or HR. Furthermore, in the subgroups receiving either an ACE inhibitor or an ARB, no effect on these hemodynamic parameters was seen as a result of concomitant DPP-4 inhibitor treatment. CONCLUSION: Adding linagliptin to treatment with ACE inhibitors or ARBs was not associated with any hemodynamic changes, supporting their concomitant use in individuals with type 2 diabetes and albuminuria.