title: Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes.
abstract: OBJECTIVE
  We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor, empagliflozin, added to multiple daily injections of insulin (MDI insulin) in obese patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Patients inadequately controlled on MDI insulin ± metformin (mean HbA1c 8.3% [67 mmol/mol]; BMI 34.8 kg/m(2); insulin dose 92 international units/day) were randomized and treated with once-daily empagliflozin 10 mg (n = 186), empagliflozin 25 mg (n = 189), or placebo (n = 188) for 52 weeks. Insulin dose was to remain stable in weeks 1-18, adjusted to meet glucose targets in weeks 19-40, then stable in weeks 41-52. The primary end point was change from baseline in HbA1c at week 18. Secondary end points were changes from baseline in insulin dose, weight, and HbA1c at week 52.
  
  
  RESULTS
  Adjusted mean ± SE changes from baseline in HbA1c were -0.50 ± 0.05% (-5.5 ± 0.5 mmol/mol) for placebo versus -0.94 ± 0.05% (-10.3 ± 0.5 mmol/mol) and -1.02 ± 0.05% (-11.1 ± 0.5 mmol/mol) for empagliflozin 10 mg and empagliflozin 25 mg, respectively, at week 18 (both P < 0.001). At week 52, further reductions with insulin titration resulted in changes from baseline in HbA1c of -0.81 ± 0.08% (-8.9 ± 0.9 mmol/mol), -1.18 ± 0.08% (-12.9 ± 0.9 mmol/mol), and -1.27 ± 0.08% (-13.9 ± 0.9 mmol/mol) with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively, and final HbA1c of 7.5% (58 mmol/mol), 7.2% (55 mmol/mol), and 7.1% (54 mmol/mol), respectively. More patients attained HbA1c <7% (<53 mmol/mol) with empagliflozin (31-42%) versus placebo (21%; both P < 0.01). Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses (-9 to -11 international units/day) and weight (-2.4 to -2.5 kg) versus placebo (all P < 0.01) at week 52.
  
  
  CONCLUSIONS
  In obese, difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses, empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX juliorosenstock@dallasdiabetes.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT.
authors.forename: Ante
authors.initials: A
authors.lastname: Jelaska
authors.affiliation: Boehringer Ingelheim France, Reims, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Frappin
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT.
authors.forename: Afshin
authors.initials: A
authors.lastname: Salsali
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kim
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin