Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.
OBJECTIVE
To investigate the efficacy and tolerability of empagliflozin as an add-on to metformin therapy in patients with type 2 diabetes.


METHODS
Patients with HbA1c levels of ≥7% to ≤ 10% (≥53 to ≤86 mmol/mol) while receiving metformin (≥1,500 mg/day) were randomized and treated with once-daily treatment with empagliflozin 10 mg (n = 217), empagliflozin 25 mg (n = 213), or placebo (n = 207) for 24 weeks. The primary end point was the change in HbA1c level from baseline at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24.


RESULTS
At week 24, adjusted mean (SE) changes from baseline in HbA1c were -0.13% (0.05)% (-1.4 [0.5] mmol/mol) with placebo, -0.70% (0.05)% (-7.7 [0.5] mmol/mol) with empagliflozin 10 mg, and -0.77% (0.05)% (-8.4 [0.5] mmol/mol) with empagliflozin 25 mg (both P < 0.001). Empagliflozin significantly reduced MDG level and systolic and diastolic blood pressure (BP) versus placebo. Adjusted mean (SE) changes from baseline in weight were -0.45 kg (0.17 kg) with placebo, -2.08 kg (0.17 kg) with empagliflozin 10 mg, and -2.46 kg (0.17 kg) with empagliflozin 25 mg (both P < 0.001). Adverse events (AEs) were similar across groups (placebo 58.7%; empagliflozin 49.5-57.1%). Confirmed hypoglycemic AEs were reported in 0.5%, 1.8%, and 1.4% of patients receiving placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Events consistent with urinary tract infections were reported in 4.9%, 5.1%, and 5.6% of patients, and events consistent with genital infections were reported in 0%, 3.7%, and 4.7% of patients, respectively.


CONCLUSIONS
Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin therapy significantly improved glycemic control, weight, and BP, and were well-tolerated.
University of Tübingen, Tübingen, Germany hans-ulrich.haering@med.uni-tuebingen.de.
Hans-Ulrich
HU
Häring
Diabetes-und Nierenzentrum, Dormagen, Germany.
Ludwig
L
Merker
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Elke
E
Seewaldt-Becker
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Marc
M
Weimer
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Thomas
T
Meinicke
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Uli C
UC
Broedl
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Hans J
HJ
Woerle
D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001835:Body Weight; D015331:Cohort Studies; 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; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D013997:Time Factors
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; C570240:empagliflozin