Efficacy and Safety of Linagliptin As Add-on Therapy to Basal Insulin in Patients with Type 2 Diabetes

This multicenter, randomized, placebo-controlled, phase 3 study evaluated the efficacy and safety of the DPP-4 inhibitor linagliptin as add-on therapy to basal insulin alone or in combination with metformin and/or pioglitazone in patients with type 2 diabetes. A total of 1261 patients inadequately controlled on insulin glargine, insulin detemir, or NPH insulin were randomized to receive either linagliptin 5 mg qd or placebo for at least 52 weeks. The primary efficacy endpoint was the mean change in A1C from baseline to Week 24, during which time the basal insulin dose remained stable. This predefined interim analysis incorporates all safety and tolerability data up to the interim timepoint (mean exposure: linagliptin, 304 days; placebo, 296 days). Mean (SD) baseline characteristics were similar in the linagliptin vs placebo groups: age, 59.7 (9.9) vs 60.4 (10.0) yrs; BMI, 30.8 (5.4) vs 31.2 (5.0) kg/m2; A1C, 8.3% (0.9%) both; basal insulin dose, 41.6 (31.9) vs 40.1 (27.3) IU/day. The placebo-adjusted mean change in A1C from baseline to Week 24 was -0.65% (p<0.0001; Figure). The overall frequency of adverse events (linagliptin, 71.8%; placebo, 72.5%) and hypoglycemia (linagliptin, 25.7%; placebo, 27.3%) were similar in both groups. Mean (SE) body weight did not change significantly from baseline (linagliptin, -0.17 (0.11) kg; placebo, +0.13 (0.12) kg; p=0.07). In conclusion, the addition of linagliptin to patients inadequately controlled on basal insulin therapy achieved significant and clinically meaningful improvements in glycemic control without weight gain and no additional risk of hypoglycemia.