Aim: To examine the options for add-on therapy in patients with type 2 diabetes whose disease is no longer adequately controlled by lifestyle interventions and oral antidiabetic drug (OAD)monotherapy.
Methods: This analysis included a subset of patients receiving prior OAD monotherapy from 2 phase 3, 26-week, randomized, double-blind, double-dummy, active-control, parallel-group, multicenter, multinational trials. Prior to randomization, patients not already receiving either metformin or glimepiride were switched to monotherapy with one of these drugs, and the dose was titrated to defined targets. Patients were then randomized to liraglutide (1.8 mg, 1.2 mg, or 0.6 mg once daily), placebo (OAD monotherapy plus placebo), or active comparator (rosiglitazone or glimepiride). For this analysis, only the liraglutide 1.8-mg dose was included. The primary outcome measure was change in glycosylated hemoglobin (HbA1c) from baseline. Secondary endpoints included in this analysis are percentage of patients achieving HbA1c < 7%, change in fasting plasma glucose, systolic blood pressure, body weight, beta-cell function, hypoglycemic episodes, and nausea.
Results: There was a significant reduction in HbA1c in patients previously treated with OAD monotherapy (P < 0.0001) and significantly more patients achieved HbA1c < 7% (P = 0.0005) with the addition of liraglutide than with rosiglitazone. In addition, rosiglitazone plus glimepiride was associated with significantly more weight gain (P < 0.0001) than liraglutide plus glimepiride (P = 0.04). For patients on metformin monotherapy, the addition of liraglutide or glimepiride resulted in similar levels of glycemic control; however, patients receiving glimepiride had significantly greater weight gain (P < 0.0001) and higher rates of minor hyperglycemia.
Conclusion: Given the combination of effective glycemic control and weight benefits, liraglutide is a good option for early add-on therapy for patients on OAD monotherapy.
Trial registration: ClinicalTrials.gov NCT00318422 NCT00318461.