Empagliflozin protects against CV risk factors in type 2 diabetes
Empagliflozin treatment in patients with type 2 diabetes mellitus (T2DM) exerts beneficial effects on cardiovascular (CV) risk factors, including blood pressure (BP) and uric acid, according to a systematic review and meta-analysis.
Researchers searched multiple online databases for randomized, double-blind, placebo-controlled trials evaluating the effects of empagliflozin on blood glucose or BP in patients with T2DM. Inclusion criteria were a follow-up of at least 4 weeks, comparable baseline data between empagliflozin and placebo, and accurate description of statistical method.
The meta-analysis included 12 trials involving 5,781 patients who had been randomized to receive empagliflozin 10 or 25 mg or placebo alone or in addition to background therapy with a mean follow-up of 28 weeks. Patients had T2DM with or without comorbid hypertension.
Pooled data showed that empagliflozin at the 10- or 25-mg dose reduced systolic and diastolic BP, uric acid, glycated haemoglobin (HbA1c), fasting plasma glucose, and body weight in T2DM patients (p<0.001 for all). The glucose-lowering drug conferred no benefits for estimated glomerular filtration rate (p>0.05).
Changes in HbA1c, systolic and diastolic BP, body weight, and lipid profile may partially explain the cardiovascular benefits observed with empagliflozin, according to researchers. These are unlikely to be the main mechanism, as significant outcome benefits were still observed despite adjustments for these factors.
Researchers proposed that several direct effects, not directly mediated by sodium glucose cotransporter 2 inhibition, are partly responsible for the demonstrated cardioprotective effects of the drug. Empagliflozin could have additive cardioprotective effects through the activation of nonclassic renin-angiotensin-aldosterone system pathways, which contribute to reduced risk of CV events.
Furthermore, the drug has been associated with increased glucagon response after meals, with glucagon reported to have positive inotropic and chronotropic effects on the myocardium and help facilitate myocardial glucose uptake even at physiological levels. Therefore, glucagon might be very important for the CV system in T2DM, researchers added.