The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial
Sepehr Gohari, Tara Reshadmanesh, Hadi Khodabandehloo, Amir Karbalaee‐Hasani, Hassan Ahangar, Shahram Arsang‐Jang, Faramarz Ismail‐Beigi, Mohsen Dadashi, Samin Ghanbari, Homa Taheri, Mojtaba Fathi, Muhammad Javad Muhammadi, Reyhaneh Mahmoodian, Atieh Asgari, Mohammadreza Tayaranian, Mehdi Moharrami, Mahsa Mahjani, Bijan Ghobadian, Hossein Chiti, Sheida Gohari
Abstract
Abstract Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured. A total of 95 patients (41.05% male, mean age 62.85 ± 7.91 years, mean HbA 1c 7.89 ± 0.96%) with concomitant T2DM and coronary artery disease (CAD) were randomized (1:1) to receive empagliflozin (10 mg/daily) or placebo. Patients treated with empagliflozin had lower levels of interleukin 6 (IL-6) (adjusted difference (adiff): − 1.06 pg/mL, 95% CI − 1.80; − 0.32, P = 0.006), interleukin 1 β (IL-1 β ) and high-sensitive C-reactive protein (Hs-CRP) (adiff: − 4.58 pg/mL and − 2.86 mg/L; P = 0.32 and 0.003, respectively) compared to placebo. There were elevations in super oxidase dismutase (SOD) activity, glutathione (GSHr), and total antioxidant capacity (TAC) with empagliflozin (adiff: 3.7 U/mL, 0.57 muM, and 124.08 mmol/L, 95% CI 1.36; 6.05, 0.19; 0.95, and 47.98; 200.18, P = 0.002, 0.004, and 0.002, respectively). While reactive oxygen species (ROS) improved significantly (adiff: − 342.51, 95% CI − 474.23; − 210.79, P < 0.001), the changes in catalase activity (CAT), malondialdehyde (MDA), or protein carbonyl groups (PCG) were not significant. Moreover, the P-selectin antigen expression on platelet surface was significantly reduced (adiff: − 8.81, 95% CI − 14.87; − 2.75, P = 0.005). Markers of glycemic status (fasting blood glucose, HbA 1c , and HOMA-IR (homeostatic model assessment for insulin resistance) significantly improved (P < 0.001). Among patients with T2DM and CAD, 6-month treatment with empagliflozin can mitigate inflammation, platelet activity and oxidative stress and is associated with clinical cardiovascular benefits. Trial Registration Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective