It has not gone unnoticed that there are multiple competing pathologies in diabetes that weigh as heavily or even more heavily on the scale of risk factors than glucose. Glucose control has not been shown to improve macrovascular outcomes (MI, stroke). On the other hand, BP control and lipid control have been shown to have more broad favorable impact, extending beyond microvascular endpoints to include macrovascular benefit. SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin), in addition to lowering glucose by enhancing urinary glucose excretion, are also associated with BP reduction, a combination that has great appeal since diabetics suffer a disproportionate burden of hypertensive cardiovascular disease.
Baker et al performed a meta-analysis of the BP effects of SGLT2 inhibitors. Their data analysis included not only agents FDA-approved for use in the United States, but also agents with data reported in Phase 2 and 3 clinical trials not yet approved in the United States (e.g., empagliflozin, ipragliflozin, remogliflozin).
From clinical trial data, SGLT2 inhibitors reduce SBP by a mean of 4 mmHg. While this may seem a modest amount, it should be recognized that the population studied was not exclusively hypertensive. Rather, the baseline SBP mean among the 27 trials they assessed (n = 12,960) ranged from 123-140 mmHg. In addition to their favorable effects upon glucose, SGLT2 inhibitors favorably affect BP.
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