title: Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes.
abstract: OBJECTIVE
  To investigate the long-term safety and efficacy of empagliflozin, a sodium glucose cotransporter 2 inhibitor; sitagliptin; and metformin in patients with type 2 diabetes.
  
  
  METHODS
  In this randomized, open-label, 78-week extension study of two 12-week, blinded, dose-finding studies of empagliflozin (monotherapy and add-on to metformin) with open-label comparators, 272 patients received 10 mg empagliflozin (166 as add-on to metformin), 275 received 25 mg empagliflozin (166 as add-on to metformin), 56 patients received metformin, and 56 patients received sitagliptin as add-on to metformin.
  
  
  RESULTS
  Changes from baseline in HbA1c at week 90 were -0.34 to -0.63% (-3.7 to -6.9 mmol/mol) with empagliflozin, -0.56% (-6.1 mmol/mol) with metformin, and -0.40% (-4.4 mmol/mol) with sitagliptin. Changes from baseline in weight at week 90 were -2.2 to -4.0 kg with empagliflozin, -1.3 kg with metformin, and -0.4 kg with sitagliptin. Adverse events (AEs) were reported in 63.2-74.1% of patients on empagliflozin and 69.6% on metformin or sitagliptin; most AEs were mild or moderate in intensity. Hypoglycemic events were rare in all treatment groups, and none required assistance. AEs consistent with genital infections were reported in 3.0-5.5% of patients on empagliflozin, 1.8% on metformin, and none on sitagliptin. AEs consistent with urinary tract infections were reported in 3.8-12.7% of patients on empagliflozin, 3.6% on metformin, and 12.5% on sitagliptin.
  
  
  CONCLUSIONS
  Long-term empagliflozin treatment provided sustained glycemic and weight control and was well tolerated with a low risk of hypoglycemia in patients with type 2 diabetes.
authors.affiliation: Corresponding author: Ele Ferrannini, ferranni@ifc.cnr.it.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Andreas
authors.initials: A
authors.lastname: Berk
authors.forename: Stefan
authors.initials: S
authors.lastname: Hantel
authors.forename: Sabine
authors.initials: S
authors.lastname: Pinnetti
authors.forename: Thomas
authors.initials: T
authors.lastname: Hach
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1; D005960:Glucosides / Q000008:administration & dosage*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C570240:empagliflozin