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Linagliptin/Metformin Combination vs Linagliptin Monotherapy for Type 2 Diabetes

Earlier treatment for poorly controlled type 2 diabetes patients is advocated…

Researchers from the University of Calgary, Alberta, Canada, evaluated glucose-lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycemia, a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted.

A total of 316 patients, with type 2 diabetes diagnosed for ≤12 months and with glycated haemoglobin (HbA1c) concentration in the range 8.5-12.0%, were randomized 1:1 to double-blind, free-combination treatment with linagliptin 5 mg once daily and metformin twice daily (uptitrated to 2000 mg/day maximum) or to linagliptin monotherapy. The primary endpoint was change in HbA1c concentration from baseline at week 24 (per-protocol completers’ cohort: n = 245).

The mean (standard deviation) age and HbA1c at baseline were 48.8 (11.0) years and 9.8 (1.1)%, respectively. At week 24, the mean ± standard error (s.e.) HbA1c decreased from baseline by -2.8 ± 0.1% with linagliptin/metformin and -2.0 ± 0.1% with linagliptin; a treatment difference of -0.8% (95% confidence interval -1.1 to -0.5; p <0.0001). Similar results were observed in a sensitivity analysis based on intent-to-treat principles: adjusted mean ± s.e. changes in HbA1c of -2.7 ± 0.1% and -1.8 ± 0.1%, respectively; treatment difference of -0.9% (95% CI -1.3 to -0.6; p <0.0001). A treatment response of HbA1c <7.0% was achieved by 61 and 40% of patients in the linagliptin/metformin and linagliptin groups, respectively. Few patients experienced drug-related adverse events (8.8 and 5.7% of patients in the linagliptin/metformin and linagliptin groups, respectively). Hypoglycemia occurred in 1.9 and 3.2% of patients in the linagliptin/metformin and linagliptin groups, respectively (no severe episodes). Body weight decreased significantly with the combination therapy (-1.3 kg between-group difference; p =0.0033).

The authors concluded that, “Linagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia, an understudied group, elicited significant improvements in glycemic control with a low incidence of hypoglycemia, weight gain or other adverse effects. These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycemia may be effectively managed with oral, non-insulin therapy.”

Practice Pearls:

  • Combination treatment of linagliptin with metformin can be very effective in term of glycemic control.
  • There were few adverse effects in this combination treatment.
  • Early initiation of combination of linagliptin with metformin would help patients achieving a mean HbA1C of 7.0% and reduce the risk of microvascular complications.

Ross S, Caballero A, Prato S et al. Initial combination of linagliptin and metformin compared with linagliptin monotherapy in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia: a randomized, double-blind, active-controlled, parallel group, multinational clinical trial. Diabetes, obesity and metabolism 2015; 17:136-44.