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

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.