Initial Combination of Empagliflozin and Linagliptin in Subjects With Type 2 Diabetes
Open Access
- 29 January 2015
- journal article
- research article
- Published by American Diabetes Association in Diabetes Care
- Vol. 38 (3), 394-402
- https://doi.org/10.2337/dc14-2365
Abstract
OBJECTIVE: To evaluate the efficacy and safety of empagliflozin/linagliptin in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: Subjects not receiving antidiabetes therapy for ≥12 weeks were randomized to empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 135), empagliflozin 10 mg (n = 134), or linagliptin 5 mg (n = 135) for 52 weeks. The primary end point was change from baseline in HbA1c at week 24. RESULTS: Mean HbA1c at baseline was 7.99–8.05% (64 mmol/mol). At week 24, adjusted mean (SE) changes from baseline in HbA1c with empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg were −1.08 (0.06)% (−11.8 [0.7] mmol/mol), −1.24 (0.06)% (−13.6 [0.7] mmol/mol), −0.95 (0.06)% (−10.4 [0.7] mmol/mol), −0.83 (0.06)% (−9.1 [0.7] mmol/mol), and −0.67 (0.06)% (−7.3 [0.7] mmol/mol), respectively. Reductions in HbA1c were significantly greater for empagliflozin 25 mg/linagliptin 5 mg compared with linagliptin 5 mg (P < 0.001) but not compared with empagliflozin 25 mg and were significantly greater for empagliflozin 10 mg/linagliptin 5 mg compared with the individual components (P < 0.001 for both). At week 24, 55.4%, 62.3%, 41.5%, 38.8%, and 32.3% of subjects with baseline HbA1c ≥7% (≥53 mmol/mol) reached HbA1c <7% with empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg, respectively. Efficacy was maintained at week 52. The proportion of subjects with adverse events (AEs) over 52 weeks was similar across groups (68.9–81.5%), with no confirmed hypoglycemic AEs. CONCLUSIONS: Reductions from baseline in HbA1c with empagliflozin/linagliptin were significantly different versus linagliptin and empagliflozin 10 mg but not versus empagliflozin 25 mg. Empagliflozin/linagliptin was well tolerated.Keywords
Funding Information
- Eli Lilly
- Boehringer Ingelheim
This publication has 19 references indexed in Scilit:
- Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trialThe Lancet Diabetes & Endocrinology, 2013
- Pathophysiologic Approach to Therapy in Patients With Newly Diagnosed Type 2 DiabetesDiabetes Care, 2013
- Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks' treatment with empagliflozin once daily in patients with type 2 diabetesDiabetes, Obesity and Metabolism, 2013
- Emerging DPP-4 inhibitors: focus on linagliptin for type 2 diabetesDiabetes, Metabolic Syndrome and Obesity, 2013
- Long-term safety and efficacy of linagliptin as monotherapy or in combination with other oral glucose-lowering agents in 2121 subjects with type 2 diabetes: up to 2 years exposure in 24-week phase III trials followed by a 78-week open-label extensionInternational Journal of Clinical Practice, 2012
- Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered ApproachDiabetes Care, 2012
- Empagliflozin, a novel selective sodium glucose cotransporter‐2 (SGLT‐2) inhibitor: characterisation and comparison with other SGLT‐2 inhibitorsDiabetes, Obesity and Metabolism, 2011
- Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trialDiabetes, Obesity and Metabolism, 2010
- (R)-8-(3-Amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a Novel Xanthine-Based Dipeptidyl Peptidase 4 Inhibitor, Has a Superior Potency and Longer Duration of Action Compared with Other Dipeptidyl Peptidase-4 InhibitorsThe Journal of pharmacology and experimental therapeutics, 2008
- Contraindications to metformin therapy in patients with Type 2 diabetes—a population‐based study of adherence to prescribing guidelinesDiabetic Medicine, 2001