Anti-inflammatory effects of empagliflozin in patients with type 2 diabetes and insulin resistance

• Published in: Diabetology and metabolic syndrome Vol. 10; no. 1; p. 93
• Main Author: Hattori, Sachiko
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.12.2018; BioMed Central; BMC
• Subjects: Alanine; Alanine transaminase; Aspartate aminotransferase; Blood pressure; C-reactive protein; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Complications and side effects; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetics; Diagnosis; Drug therapy; Empagliflozin; Fasting; Glucose; Health aspects; High density lipoprotein; High sensitivity CRP; Inflammation; Insulin; Insulin resistance; Lipoproteins; Low density lipoprotein; Patient outcomes; Patients; Proteins; Risk factors; Sodium-glucose co-transporter-2 inhibitor; Software; Standard deviation; Statistical analysis; Triglycerides; Type 2 diabetes; γ-Glutamyltransferase; Sodium-glucose co-transporter-2 inhibitor; High sensitivity CRP; Insulin resistance
• ISSN: 1758-5996; 1758-5996
• DOI: 10.1186/s13098-018-0395-5

Inflammation might be a pathological mediator of cardiovascular events in patients with type 2 diabetes and high cardiovascular risk. We 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. Empagliflozin 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. Empagliflozin 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. UMIN Clinical Registry (UMIN000021552). Registered 21 March 2016, https://upload.umin.ac.jp/UMIN000021552.