The effect of dapagliflozin on apolipoprotein B and glucose fluxes in patients with type 2 diabetes and well‐controlled plasma LDL cholesterol. Issue 6 (27th February 2020)

• Record Type: Journal Article
• Authors: Bouter, Kristien E. C.; van Bommel, Erik J. M.; Jansen, Hans; van Harskamp, Dewi; Schierbeek, Henk; Ackermans, Mariëtte T.; Serlie, Mireille J.; Schimmel, Alinda W. M.; Nieuwdorp, Max; Dallinga‐Thie, Geesje M.; van Raalte, Daniël H.
• Is Part Of: Diabetes, obesity & metabolism. Volume 22:Issue 6(2020)
• Page Start: 988
• Page End: 996
• Publication Date: 2020-02-27
• Subjects: apolipoprotein B -- dapagliflozin -- glucose -- insulin sensitivity -- LDL cholesterol -- lipolysis -- sodium‐glucose co‐transporter‐2 inhibitor -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13990
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aim: To dissect the effects of the sodium‐glucose linked transporter 2 inhibitor dapagliflozin on lipid metabolism and assess whether these effects could potentially offset cardiovascular benefit with this drug‐class. Materials and Methods: We assessed the effect of dapagliflozin on lipid metabolism in 11 adults with uncomplicated type 2 diabetes. After 4 weeks of statin wash‐out and 4 weeks of rosuvastatin 10 mg treatment, participants were treated with dapagliflozin 10 mg once‐daily for 5 weeks. Before and after dapagliflozin, plasma lipids were measured and very low‐density lipoprotein (VLDL)‐1 and VLDL‐2 apolipoprotein (Apo)B fluxes were assessed using (5.5.5‐ 2 H3 )‐leucine tracer infusion. In addition, hepatic and peripheral insulin sensitivity as well as insulin‐mediated inhibition of peripheral lipolysis were measured during a two‐step hyperinsulinemic‐euglycaemic clamp using (6, 6‐ 2 H2 )‐glucose and (1, 1, 2, 3, 3‐ 2 H5 )‐glycerol tracers. Results: Rosuvastatin decreased all plasma lipids significantly: total cholesterol from 4.5 (3.2–6.2) to 3.1 (2.5–3.8) mmol/L, LDL cholesterol from 2.6 (1.7–3.4) to 1.5 (1.1–2.2) mmol/L, HDL cholesterol from 1.34 (0.80–2.02) to 1.19 (0.74–1.89) mmol/L and triglycerides from 0.92 (0.31–3.91) to 0.79 (0.32–2.10) mmol/L . The addition of dapaglifozin to rosuvastatin did not raise either LDL cholesterol or total cholesterol, and only increased HDL cholesterol by 0.08 (−0.03–0.13) mmol/L ( P = 0.03). In line with this, dapagliflozin did not affect VLDL‐1 or VLDL‐2 ApoB fluxes. Fasting endogenous glucose production tended to increase by 0.9 (−3.4–3.1) μmol kg −1 min −1 ( P = 0.06), but no effect on hepatic and peripheral insulin sensitivity or on peripheral lipolysis was observed. Conclusions: Dapagliflozin has no effect on plasma LDL‐cholesterol levels or VLDL‐apoB fluxes in the context of optimal lipid‐lowering treatment, which will thus not limit cardiovascular benefit when lipids are adequately controlled.