Effects of 6 weeks of treatment with dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo‐controlled, exploratory study. Issue 7 (12th March 2021)

• Record Type: Journal Article
• Authors: Oldgren, Jonas; Laurila, Sanna; Åkerblom, Axel; Latva‐Rasku, Aino; Rebelos, Eleni; Isackson, Henrik; Saarenhovi, Maria; Eriksson, Olof; Heurling, Kerstin; Johansson, Edvin; Wilderäng, Ulrica; Karlsson, Cecilia; Esterline, Russell; Ferrannini, Ele; Oscarsson, Jan; Nuutila, Pirjo
• Is Part Of: Diabetes, obesity & metabolism. Volume 23:Issue 7(2021)
• Page Start: 1505
• Page End: 1517
• Publication Date: 2021-03-12
• Subjects: dapagliflozin -- SGLT2 inhibitor -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.14363
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aim: To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. Materials and Methods: Patients with type 2 diabetes on metformin treatment were randomized to double‐blind, 6‐week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [ 11 C]‐acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [ 18 F]‐6‐thia‐heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. Results: Evaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m 2 and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (−0.095 [−0.145, −0.043] J/g/min) and LV oxygen consumption were significantly reduced (−0.30 [−0.49, −0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was −3.19 (−6.32, −0.07) mL/m 2 ( p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (−3.92% [−7.57%, −0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] μmol/g/min; p = .018), while cardiac uptake was unchanged. Conclusions: This exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.