title: Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes.
abstract: OBJECTIVE
  To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes.
  
  
  METHODS
  We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment.
  
  
  RESULTS
  In the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% (P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring (CGM) of 148.8 mg/dL (8.3 mmol/L) (P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) (P = 0.002) in HbA1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3 mg/dL (9.5 mmol/L), and a decrease of 0.06% (0.65 mmol/mol) in HbA1c. The percentage of time in target glucose range 70-180 mg/dL (3.9-10.0 mmol/L) increased from baseline with sotagliflozin compared with placebo, to 68.2% vs. 54.0% (P = 0.003), while the percentage of time in hyperglycemic range >180 mg/dL (10.0 mmol/L) decreased from baseline, to 25.0% vs. 40.2% (P = 0.002), for sotagliflozin and placebo, respectively. Body weight decreased (1.7 kg) with sotagliflozin compared with a 0.5 kg gain (P = 0.005) in the placebo group.
  
  
  CONCLUSIONS
  As adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes.
authors.affiliation: Lexicon Pharmaceuticals, Inc., The Woodlands, TX arthur.sands@bcm.edu pstrumph@lexpharma.com.
authors.forename: Arthur T
authors.initials: AT
authors.lastname: Sands
authors.affiliation: Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Zambrowicz
authors.affiliation: Dallas Diabetes and Endocrine Center, Dallas, TX.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapuerta
authors.affiliation: Atlanta Diabetes Associates, Atlanta, GA.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Bode
authors.affiliation: University of Colorado Denver/Barbara Davis Center for Childhood Diabetes, Aurora, CO.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Garg
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
authors.forename: Phillip
authors.initials: P
authors.lastname: Banks
authors.affiliation: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY.
authors.forename: Rubina
authors.initials: R
authors.lastname: Heptulla
authors.affiliation: Creighton Diabetes Center, Omaha, NE.
authors.forename: Marc
authors.initials: M
authors.lastname: Rendell
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA.
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.affiliation: Lexicon Pharmaceuticals, Inc., The Woodlands, TX arthur.sands@bcm.edu pstrumph@lexpharma.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Strumph
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D003131:Combined Modality Therapy; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage*; D006027:Glycosides / Q000008:administration & dosage*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006027:Glycosides; D007004:Hypoglycemic Agents; D007328:Insulin; C529054:dapagliflozin; C575681:(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol