title: Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia.
abstract: OBJECTIVE
  To evaluate the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin added to metformin for 12 weeks in patients with type 2 diabetes.
  
  
  METHODS
  This dose-ranging, double-blind, placebo-controlled trial randomized 495 participants with type 2 diabetes inadequately controlled on metformin [haemoglobin A1c (HbA1c) >7 to ≤10%] to receive 1, 5, 10, 25, or 50 mg empagliflozin once daily (QD), or placebo, or open-label sitagliptin (100 mg QD), added to metformin for 12 weeks. The primary endpoint was change in HbA1c from baseline to week 12 (empagliflozin groups versus placebo).
  
  
  RESULTS
  Reductions in HbA1c of -0.09 to -0.56% were observed with empagliflozin after 12 weeks, versus an increase of 0.15% with placebo (baseline: 7.8-8.1%). Compared with placebo, empagliflozin doses from 5 to 50 mg resulted in reductions in fasting plasma glucose (-2 to -28 mg/dl vs. 5 mg/dl with placebo; p < 0.0001) and body weight (-2.3 to -2.9 kg vs. -1.2 kg; p < 0.01). Frequency of adverse events was generally similar with empagliflozin (29.6-48.6%), placebo (36.6%) and sitagliptin (35.2%). Hypoglycaemia rates were very low and balanced among groups. Most frequent adverse events with empagliflozin were urinary tract infections (4.0% vs. 2.8% with placebo) and pollakiuria (2.5% vs. 1.4% with placebo). Genital infections were reported only with empagliflozin (4.0%).
  
  
  CONCLUSIONS
  Once daily empagliflozin as add-on therapy to metformin was well tolerated except for increased genital infections and resulted in reductions in HbA1c, fasting plasma glucose and body weight in patients with type 2 diabetes inadequately controlled on metformin monotherapy.
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rosenstock
authors.forename: L J
authors.initials: LJ
authors.lastname: Seman
authors.forename: A
authors.initials: A
authors.lastname: Jelaska
authors.forename: S
authors.initials: S
authors.lastname: Hantel
authors.forename: S
authors.initials: S
authors.lastname: Pinnetti
authors.forename: T
authors.initials: T
authors.lastname: Hach
authors.forename: H J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000704:Analysis of Variance; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006400:Hematocrit / Q000379:methods; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
keywords: HbA1c; SGLT2 inhibitor; add-on therapy; blood pressure; body weight; empagliflozin; tolerability