Trading Glucose Control for Hypertension: Lessons from Mother Nature

  1. Robert Chilton, DO, FACC, FAHA


Brown NJ, Byiers S, Carr D, Maldonado M, Warner BA: Dipeptidyl peptidase-IV inhibitor associated with increased risk of ACE inhibitor-associated angioedema. Hypertension 54:516–523, 2009


Objective. Dipeptidyl peptidase-4 (DPP-4) inhibitors decrease degradation of the incretins and peptides such as substance P that may be involved in the pathogenesis of ACE inhibitor–associated angioedema. This study sought to determine the effect of DPP-4 inhibition on patients' risk of developing clinical angioedema.

Design. The authors compared the incidence of angioedema in patients treated with the DPP-4 inhibitor vildagliptin to that of patients treated with a comparator in phase 3 randomized clinical trials. Prospectively defined angioedema-related events in these trials were adjudicated by a blinded internal medicine committee and an expert reviewer. Patients' concurrent use of ACE inhibitors or angiotensin-receptor blockers (ARBs) was ascertained from case report forms. Odds ratios (ORs) and 95% confidence intervals (CIs) comparing the angioedema risk in vildagliptin- and comparator-treated patients were calculated for the full population as well as for the subset of patients taking ACE inhibitors or ARBs, using both an analysis of pooled data and a meta-analysis.

Results. Overall, the researchers found no association between vildagliptin use and angioedema. However, meta-analysis revealed that, among individuals taking an ACE inhibitor, vildagliptin use was associated with an increased risk of angioedema (14 cases among 2,754 vildagliptin users vs. 1 case among 1,819 comparator users, OR 4.57, 95% CI 1.57–13.28).

Conclusion. Vildagliptin use may be linked with an increased risk of angioedema among patients who also take ACE inhibitors, although the absolute risk is small. Health care providers confronted with angioedema in a patient taking an ACE inhibitor and a DPP-4 inhibitor should consider this possible drug-drug interaction.


It is estimated that the number of people with diabetes will approach 366 million by 2030.1 This not only increases the risk …

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