title: Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes.
abstract: To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes.
  
  
  
  In this single-centre, double-blind trial, we randomized 50 obese adults without diabetes (aged 18-70 years; body mass index 30-45 kg/m2) to oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo. MRI was used to assess change in body composition. Participants were instructed to follow a balanced diet and exercise moderately.
  
  
  
  Of 25 dapagliflozin/exenatide- and 25 placebo-treated participants, 23 (92.0%) and 20 (80.0%) completed 24 weeks of treatment, respectively. At baseline, the mean participant age was 52 years, 61% were female, the mean body weight was 104.6 kg, and 73.5% of participants had prediabetes (impaired fasting glucose or impaired glucose tolerance). After 24 weeks, for dapagliflozin/exenatide versus placebo: the difference in body weight change was -4.13 kg (95% confidence interval -6.44, -1.81; P < .001), which was mostly attributable to adipose tissue reduction without lean tissue change; 36.0% versus 4.2% of participants achieved ≥5% body weight loss, respectively; and prediabetes was less frequent with active treatment (34.8% vs 85.0%, respectively; P < .01). The difference in SBP change for dapagliflozin/exenatide versus placebo was -6.7 mm Hg. As expected, nausea and injection-site reactions were more frequent with dapagliflozin/exenatide than with placebo. Only two and three participants, respectively, discontinued because of adverse events.
  
  
  
  Compared with placebo, dapagliflozin/exenatide dual therapy reduced body weight, frequency of prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Lundkvist
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: C David
authors.initials: CD
authors.lastname: Sjöström
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Sam
authors.initials: S
authors.lastname: Amini
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pereira
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Johnsson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Eriksson
mesh_terms: D000273:Adipose Tissue / Q000000981:diagnostic imaging; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001823:Body Composition; D001835:Body Weight; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D018149:Glucose Intolerance / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use*; D011236:Prediabetic State / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D014688:Venoms / Q000627:therapeutic use*; D015431:Weight Loss
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; C529054:dapagliflozin; D000077270:Exenatide
keywords: dapagliflozin; exenatide; obesity; prediabetes