Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c ≤ 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials
Open Access
- 23 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Diabetes Therapy
- Vol. 11 (6), 1317-1330
- https://doi.org/10.1007/s13300-020-00819-9
Abstract
Introduction Clinical guidelines suggest a glycated hemoglobin A1c (HbA1c) target of ≤ 6.5% for type 2 diabetes patients with short duration of disease, few comorbidities and/or long life expectancy—provided this goal can be achieved safely. We explored whether initial combination treatment with the dipeptidyl peptidase-4 inhibitor linagliptin and metformin could provide better glycemic control (HbA1c ≤ 6.5%) than metformin alone without increasing hypoglycemia. Methods We pooled and analyzed individual patient data from two randomized clinical trials of early combination therapy with linagliptin and metformin versus metformin monotherapy. The primary outcome in both trials was the change in HbA1c from baseline to week 24. We evaluated the percentage of patients who achieved HbA1c ≤ 6.5% at week 24 and the incidence of adverse events. Results Most (> 70%) of the 1160 patients analyzed were treatment naive, and more than half had had diabetes for ≤ 1 year; mean baseline HbA1c was approximately 8.7%. Combination therapy with linagliptin and metformin resulted in more patients achieving HbA1c ≤ 6.5% than metformin alone, both for a metformin dose of 500 mg (40.1 vs. 22.9%, respectively, odds ratio [OR] 2.84, 95% confidence interval [CI] 1.87–4.32) and 1000 mg (49.5 vs. 35.4%, respectively, OR 2.28, 95% CI 1.54–3.40). Hypoglycemia occurred in < 3% of patients, with a comparable incidence between treatment groups. Other adverse events were also balanced between groups. Conclusion Early combination treatment with linagliptin and metformin can improve the chances of achieving tight glycemic control (HbA1c ≤ 6.5%) without increasing the risk of hypoglycemia or other adverse events. Trial Registration ClinicalTrials.gov, NCT00798161 and NCT01708902.Keywords
Funding Information
- Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance
This publication has 40 references indexed in Scilit:
- Current level of glycaemic control and its associated factors in patients with type 2 diabetes across Europe: data from the PANORAMA studyClinical Endocrinology, 2013
- Achievement of Goals in U.S. Diabetes Care, 1999–2010New England Journal of Medicine, 2013
- Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trialCurrent Medical Research and Opinion, 2012
- Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double‐blind, placebo‐controlled studyDiabetes, Obesity and Metabolism, 2012
- Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled studyDiabetes, Obesity and Metabolism, 2010
- Linagliptin (BI 1356), a potent and selective DPP‐4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetesDiabetic Medicine, 2010
- 10-Year Follow-up of Intensive Glucose Control in Type 2 DiabetesNew England Journal of Medicine, 2008
- Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 DiabetesNew England Journal of Medicine, 2008
- Effects of Intensive Glucose Lowering in Type 2 DiabetesNew England Journal of Medicine, 2008
- Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)The Lancet, 1998