title: Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  This study investigated the efficacy and tolerability of empagliflozin as add-on to pioglitazone ± metformin in patients with type 2 diabetes (T2DM).
  
  
  METHODS
  Patients with HbA1c ≥7 and ≤10% were randomized and treated with once daily empagliflozin 10 mg (n = 165), empagliflozin 25 mg (n = 168) or placebo (n = 165) as add-on to pioglitazone ± metformin for 24 weeks. Endpoints included changes from baseline in HbA1c (primary endpoint), fasting plasma glucose (FPG) and body weight at week 24.
  
  
  RESULTS
  Adjusted mean ± standard error changes in HbA1c were -0.6 ± 0.07% and -0.7 ± 0.07% with empagliflozin 10 mg and 25 mg, respectively, vs. -0.1 ± 0.07% with placebo (both p < 0.001). More patients with HbA1c ≥7% at baseline achieved HbA1c <7% with empagliflozin 10 mg (23.8%) and 25 mg (30.0%) vs. placebo (7.7%) (both p < 0.001). FPG decreased with empagliflozin (-0.94 mmol/l for 10 mg and -1.22 mmol/l for 25 mg) and increased with placebo (+0.36 mmol/l; both p < 0.001). Adjusted mean ± standard error changes in weight were -1.62 ± 0.21 kg and -1.47 ± 0.21 kg with empagliflozin 10 mg and 25 mg, respectively, vs. +0.34 ± 0.21 kg with placebo (both p < 0.001). Similar proportions of patients reported adverse events with empagliflozin (67.3-71.4%) and placebo (72.7%). Confirmed hypoglycaemia was reported by 1.2-2.4% of patients on empagliflozin and 1.8% on placebo.
  
  
  CONCLUSIONS
  Empagliflozin 10 mg and 25 mg once daily for 24 weeks as add-on to pioglitazone ± metformin reduced HbA1c, FPG and weight and were well tolerated in patients with T2DM.
authors.affiliation: Health Sciences Centre, Memorial University, Newfoundland, Canada.
authors.forename: C S
authors.initials: CS
authors.lastname: Kovacs
authors.forename: V
authors.initials: V
authors.lastname: Seshiah
authors.forename: R
authors.initials: R
authors.lastname: Swallow
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: H
authors.initials: H
authors.lastname: Rattunde
authors.forename: H J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: U C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones; D008687:Metformin; C570240:empagliflozin; D000077205:Pioglitazone
keywords: SGLT2; empagliflozin; glycaemic control; pioglitazone; type 2 diabetes; weight