title: Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes: a randomized placebo-controlled trial.
abstract: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce glucose levels, body weight, and blood pressure, possibly resulting in cardiovascular protection. In phase III trials, SGLT2i were shown to increase HDL cholesterol. We aimed to evaluate whether the SGLT2i dapagliflozin affects HDL function in a randomized placebo-controlled trial.
  
  
  
  Thirty-three type 2 diabetic patients were randomized to receive dapagliflozin 10 mg or placebo for 12 weeks on top of their glucose lowering medications. The primary end-point was the change in cholesterol efflux capacity (CEC) from macrophages at study end versus baseline. Secondary endpoints were changes in: distribution of HDL subfractions, lipid profile, activity of enzymes that mediate HDL antioxidant properties (PON1 and ARE) and cholesterol metabolism (CETP), HbA1c, body weight and composition.
  
  
  
  Thirty-one patients completed the study, n = 16 in the placebo group and n = 15 in the dapagliflozin group. Patients randomized to dapagliflozin were older and had lower adiposity indexes, although these differences disappeared after correction for multiple testing. Therapy with dapagliflozin reduced HbA1c by 0.9% and body weight by 3.1 kg, mainly attributable to reduction of body water and lean mass. As compared to placebo, dapagliflozin reduced CEC (-6.7 ± 2.4 versus 0.3 ± 1.8%; p = 0.043), but this effect was no longer significant after adjusting for age and BMI. No change was detected in HDL cholesterol, HDL subfractions, activity of PON1, ARE, and CETP.
  
  
  
  Despite improvements in glucose control and reduction in body weight, therapy with dapagliflozin exerted no significant effect on HDL cholesterol levels and HDL functionality. Trial registration EudraCT 2014-004270-42; NCT02327039.
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy. gianpaolofadini@hotmail.com.
authors.forename: Gian Paolo
authors.identifier: 0000-0002-6510-2097
authors.initials: GP
authors.lastname: Fadini
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
authors.forename: Benedetta Maria
authors.initials: BM
authors.lastname: Bonora
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Zatti
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Vitturi
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marescotti
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Albiero
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D008076:Cholesterol, HDL; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin
keywords: Atherosclerosis; Body composition; Therapy