title: Effect of Dapagliflozin With and Without Acipimox on Insulin Sensitivity and Insulin Secretion in T2DM Males.
abstract: OBJECTIVE
  To investigate the effect of lowering the plasma glucose and free fatty acid (FFA) concentrations with dapagliflozin and acipimox, respectively, on insulin sensitivity and insulin secretion in T2DM individuals.
  
  
  METHODS
  Fourteen male T2DM patients received an oral glucose tolerance test and euglycemic hyperinsulinemic clamp at baseline and were treated for 3 weeks with dapagliflozin (10 mg per day). During week 3, acipimox (250 mg four times per day) treatment was added to dapagliflozin. The oral glucose tolerance test and insulin clamp were repeated at the end of weeks 2 and 3.
  
  
  RESULTS
  Dapagliflozin caused glucosuria and significantly lowered the plasma glucose concentration (by 35 mg/dL; P < .01), whereas the fasting plasma FFA concentration was unaffected. Acipimox caused a further decrease in the fasting plasma glucose concentration (by 20 mg/dL; P < .01) and a significant decrease in the fasting plasma FFA concentration. Compared to baseline, insulin-mediated glucose disposal increased significantly at week 2 (from 4.48 ± 0.50 to 5.30 ± 0.50 mg/kg · min; P < .05). However, insulin-mediated glucose disposal at week 3 (after the addition of acipimox) did not differ significantly from that at week 2. Glucose-stimulated insulin secretion at week 2 increased significantly compared to baseline, and it increased further and significantly at week 3 compared to week 2.
  
  
  CONCLUSIONS
  Lowering the plasma glucose concentration with dapagliflozin improves both insulin sensitivity and β-cell function, whereas lowering plasma FFA concentration by addition of acipimox to dapagliflozin improves β-cell function without significantly affecting insulin sensitivity.
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Merovci
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Abdul-Ghani
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Solis-Herrera
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daniele
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.affiliation: Division of Diabetes (A.Me., M.A.-G., C.S.-H., J.X., G.D., D.T., R.A.D.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Institute of Biomedical Engineering (A.Ma.), National Research Council, 35127 Padova, Italy.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D000960:Hypolipidemic Agents; D007328:Insulin; D011719:Pyrazines; C529054:dapagliflozin; C027696:acipimox