Abstract
BackgroundInflammation might be a pathological mediator of cardiovascular events in patients with type 2 diabetes and high cardiovascular risk.MethodsWe investigated whether empagliflozin (EMPA) exerts anti-inflammatory effects that are reflected in decreased high-sensitivity C-reactive protein (hsCRP) values. Patients were allocated to receive a placebo (n = 51) or EMPA (n = 51) as an add-on treatment. Fasting blood samples were collected before and every 3 months after this intervention for 1 year.ResultsEmpagliflozin tended to elicit reductions in BMI, HbA1c, aspartate aminotransferase, alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase compared with the placebo, but the differences did not reach statistical significance. Levels of LDL-cholesterol, HDL-cholesterol, and triglycerides were unaltered, significantly increased, and decreased, respectively, by EMPA, but the differences were not statistically significant compared with the placebo. Empagliflozin for 12 months notably reduced the homeostatic model assessment of insulin resistance (HOMA-IR), remnant-like particle cholesterol (RLP-C), and hsCRP by 43%, 52% and 54%, respectively. The time courses of these reductions significantly differed from those of the placebo. Systolic and diastolic blood pressure were also significantly reduced by EMPA compared with the placebo. We applied multiple linear regression analysis to determine which factors were associated with changes in hsCRP induced by EMPA. The results revealed that alterations in hsCRP values (log [hsCRP at 12 months] minus log [hsCRP at month 0]) were significantly associated with changes in HOMA-IR, RLP-C, systolic blood pressure, HDL-C and ALT.ConclusionEmpagliflozin decreased hs-CRP and lowered levels of remnant related lipoproteins probably via ameliorating insulin resistance. The cardiovascular benefits conferred by EMPA might be driven at least partly by anti-inflammatory effects, and this mechanism might cooperate with other EMPA-induced changes including reduced blood pressure, to achieve the degree of cardioprotection revealed by the EMPA-REG OUTCOME trial.Trial registration UMIN Clinical Registry (UMIN000021552). Registered 21 March 2016, https://upload.umin.ac.jp/UMIN000021552
Highlights
Inflammation might be a pathological mediator of cardiovascular events in patients with type 2 diabetes and high cardiovascular risk
Levels of body mass index (BMI), hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GTP) were slightly but not significantly reduced by EMPA compared with the placebo
This study showed that the sodium– glucose cotransporter 2 inhibitor (SGLT2) inhibitor, EMPA, decreases highsensitivity C-reactive protein (hsCRP), lowers levels of remnant lipoproteins and ameliorates insulin resistance
Summary
Inflammation might be a pathological mediator of cardiovascular events in patients with type 2 diabetes and high cardiovascular risk. Ridker et al [3] recently showed that antiinflammatory therapy with canakinumab, which targets the interleukin-1β innate immunity pathway, leads to a significantly lower rate of recurrent CV events than a placebo, independently of lowering LDL-cholesterol. They showed that the magnitude of the reduction in highsensitivity C-reactive protein (hsCRP) after a single dose of canakinumab might provide a simple clinical method with which to identify individuals who are likely to benefit from continued treatment; that is, lower is better for reducing inflammation with canakinumab [4]
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