New era
antidiabetic drugs are characterized by cardiovascular safety, including specific outcome benefits observed in randomized clinical trials (RCTs). It has been postulated that the favorable effects of new
antidiabetic agents are related both to better control of blood pressure (BP) levels and to activation of multiple anti-atherosclerotic properties. In this review, we aimed to assess whether
antidiabetic drugs have a pressor effect in
glucose control and outcome-oriented RCTs, and to summarize the activated pathophysiological mechanisms relevant to BP control following the use of different
antidiabetic drug classes. We also tried to determine which, if any, are the BP-lowering effects of more intense vs less intense
glucose-lowering strategy irrespectively of trial
antidiabetic regimen. To provide more robust results and evidence-based argumentation, a meta-analysis of placebo-controlled
antidiabetic drug RCTs was undertaken to estimate the ongoing BP reduction for all considered and each separate
drug class alone. This quantitative synthesis might be helpful for the clinician 1) to select or avoid the use of some classes of
antidiabetic agents with a potential favorable or adverse pressor effect, respectively 2) to organize the overall
drug regimen in patients with
diabetes mellitus and minimize side effects because of concomitant use of drugs with established pressor effect (i.e.
antihypertensive agents). This review was also organized to indicate whether BP change associated with different
antidiabetic treatments may explain the specific macrovascular outcome benefits. Between all
antidiabetic drugs including exogenous
insulin, only
sodium-glucose cotransporter 2 inhibitors produce a clinically important BP-lowering effect, but this BP reduction alone cannot explain the observed cardiovascular benefit.