Linagliptin improved glycaemic control without weight gain or hypoglycaemia in patients with type 2 diabetes inadequately controlled by a combination of metformin and pioglitazone: a 24-week randomized, double-blind study

M Bajaj, R Gilman, S Patel, J Kempthorne-Rawson, D Lewis-D'Agostino, H-J Woerle, M Bajaj, R Gilman, S Patel, J Kempthorne-Rawson, D Lewis-D'Agostino, H-J Woerle

Abstract

Aims: To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type 2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone.

Methods: This was a multi-centre, phase 3, randomized, double-blind, placebo-controlled study comparing linagliptin 5 mg once daily (n = 183) and placebo (n = 89) as add-on to metformin and pioglitazone. The primary endpoint was the change from baseline in glycated haemoglobin (HbA1c ) after 24 weeks.

Results: The placebo-corrected adjusted mean (se) change in HbA1c from baseline to 24 weeks was -6 (1) mmol/mol [-0.57 (0.13)%] (P < 0.0001). In patients with baseline HbA1c ≥ 53 mmol/mol (7.0%), 32.4% of patients in the linagliptin group and 13.8% in the placebo group achieved HbA1c < 53 mmol/mol (7.0%) (odds ratio 2.94; P = 0.0033). The placebo-corrected adjusted mean (se) change from baseline in fasting plasma glucose at week 24 was -0.57 (0.26) mmol/l [-10.4 (4.7) mg/dl] (P = 0.0280). The incidence of serious adverse events was 2.2% with linagliptin and 3.4% with placebo. Investigator-defined hypoglycaemia occurred in 5.5% of the linagliptin group and 5.6% of the placebo group. No meaningful changes in mean body weight were noted for either group.

Conclusions: Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinically meaningful improvements in glycaemic control, without an additional risk of hypoglycaemia or weight gain (Clinical Trials Registry No: NCT 00996658).

Trial registration: ClinicalTrials.gov NCT00996658.

© 2014 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Figures

Figure 1
Figure 1
Patient allocation. FAS, full analysis set.
Figure 2
Figure 2
Adjusted mean change from baseline in HbA1c over time (full analysis set, last observation carried forward). Linagliptin 5 mg once daily (•); placebo (○).
Figure 3
Figure 3
Adjusted mean change from baseline in fasting plasma glucose over time (full analysis set, last observation carried forward). Linagliptin 5 mg once daily (•); placebo (○).
Figure 4
Figure 4
Percentage of patients achieving HbA1c < 53 mmol/mol, < 48 mmol/mol or ≥ 6 mmol/mol reduction after 24 weeks (full analysis set, non-completers were considered treatment failures). Linagliptin 5 mg once daily (■); placebo (□).

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