title: Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin.
abstract: The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies.
  
  
  
  This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. Small dense (sd) LDL-C, large buoyant (lb) LDL-C, HDL2-C, and HDL3-C levels were determined using our established homogeneous assays. Statistical comparison of blood parameters before and after treatment was performed using the paired t test.
  
  
  
  Dapagliflozin and sitagliptin comparably decreased HbA1c (0.75 and 0.63%, respectively). Dapagliflozin significantly decreased body weight, systolic blood pressure, plasma triglycerides and liver transaminases, and increased adiponectin; sitagliptin did not alter these measurements. LDL-C and apolipoprotein (apo) B were not significantly changed by dapagliflozin, whereas HDL-C and apo AI were increased. Dapagliflozin did not alter concentrations of LDL-C, but sd LDL-C decreased by 20% and lb LDL-C increased by 18%. Marked elevation in lb LDL-C (53%) was observed in individuals (n = 20) whose LDL-C was elevated by dapagliflozin. However, sd LDL-C remained suppressed (20%). Dapagliflozin increased HDL2-C by 18% without affecting HDL3-C. Sitagliptin did not alter plasma lipids or lipoprotein subspecies.
  
  
  
  A SGLT-2 inhibitor, dapagliflozin suppresses potent atherogenic sd LDL-C and increased HDL2-C, a favorable cardiometabolic marker. Although LDL-C levels are elevated by treatment with dapagliflozin, this was due to increased concentrations of the less atherogenic lb LDL-C. However, these findings were not observed after treatment with dipeptidyl peptidase-4 inhibitor, sitagliptin. Trial registration UMIN Clinical Trials Registry (UMIN000020984).
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan. t-hayashi@med.showa-u.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Fukui
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakanishi
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Tomoyasu
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Osamura
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohara
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Reagent R&D department, Denka Seiken Co., Ltd., Nihonbashi Mitsui Tower, 1-1, Nihonbashi-Muromachi 2-chome, Chuo-ku, Tokyo, 103-8338, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan. hirano@med.showa-u.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D053439:Lipoproteins, HDL2 / Q000819:agonists / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage*; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*
chemical_list: D001559:Benzhydryl Compounds; D008078:Cholesterol, LDL; D005960:Glucosides; D007004:Hypoglycemic Agents; D053439:Lipoproteins, HDL2; D051247:Sodium-Glucose Transport Proteins; C529054:dapagliflozin; D000068900:Sitagliptin Phosphate
keywords: Dapagliflozin; High-density lipoprotein 2-cholesterol; Lipoprotein subspecies; Small dense low-density lipoprotein-cholesterol; Sodium-glucose co-transporter-2 inhibitor