Characterizing effects of antidiabetic drugs on heart rate, systolic and diastolic blood pressure

A model-based meta-analysis (MBMA) was performed with reported data from obese subjects and patients with type 2 diabetes (T2DM) to characterize the effects of DPP4 inhibitors, GIP, GLP1, and dual GIP/GLP1 agonists, or a combination of these anti-diabetic drugs (ADs) on heart rate (HR), diastolic (DBP) and systolic blood pressure (SBP). A systematic literature search and review following the Cochrane method identified sources for investigational and approved ADs resulted in a comprehensive database with data from 178 clinical studies in obese subjects and patients with T2DM. Results indicated that there were AD class dependent effects on HR and SBP, whereas no clear AD-related effects on DBP were found. All AD classes except for DPP4 inhibitors increased HR. The largest increase of 12 bpm was seen with GLP1 receptor agonists. All AD classes appeared to decrease SBP. DPP4 inhibitors were associated with a marginal decrease of ~1 mmHg while GLP1 and GIP/GLP1 dual agonists exhibited the largest decrease of ~3 mmHg in SBP. AD related effects were similar in obese subjects and patients with T2DM. In conclusion, there are clinically relevant AD-related effects on both HR and SBP, but not on DBP. DPP4 inhibitors are associated with the smallest (if at all) effects on HR and SBP, whereas GLP1 inhibitors exhibited the largest effects on these two cardiovascular endpoints. Additional studies are warranted to further investigate how AD related SBP decreases combined with HR increases affect long-term cardiovascular mortality.