25298165
OBJECTIVE	To evaluate glucose-lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycaemia , a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted .
METHODS	A total of 316 patients , with type 2 diabetes diagnosed for 12months 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 5mg once daily and metformin twice daily ( uptitrated to 2000mg/day maximum ) or to linagliptin monotherapy .
METHODS	The primary endpoint was change in HbA1c concentration from baseline at week 24 ( per-protocol completers ' cohort : n = 245 ) .
RESULTS	The mean ( standard deviation ) age and HbA1c at baseline were 48.8 ( 11.0 ) years and 9.8 ( 1.1 ) % , respectively .
RESULTS	At week 24 , the meanstandard error ( s.e. ) HbA1c decreased from baseline by -2.80.1 % with linagliptin/metformin and -2.00.1 % with linagliptin ; a treatment difference of -0.8 % ( 95 % confidence interval -1.1 to -0.5 ; p < 0.0001 ) .
RESULTS	Similar results were observed in a sensitivity analysis based on intent-to-treat principles : adjusted means.e .
RESULTS	changes in HbA1c of -2.70.1 % and -1.80.1 % , respectively ; treatment difference of -0.9 % ( 95 % CI -1.3 to -0.6 ; p < 0.0001 ) .
RESULTS	A treatment response of HbA1c < 7.0 % was achieved by 61 and 40 % of patients in the linagliptin/metformin and linagliptin groups , respectively .
RESULTS	Few patients experienced drug-related adverse events ( 8.8 and 5.7 % of patients in the linagliptin/metformin and linagliptin groups , respectively ) .
RESULTS	Hypoglycaemia occurred in 1.9 and 3.2 % of patients in the linagliptin/metformin and linagliptin groups , respectively ( no severe episodes ) .
RESULTS	Body weight decreased significantly with the combination therapy ( -1.3 kg between-group difference ; p = 0.0033 ) .
CONCLUSIONS	Linagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia , an understudied group , elicited significant improvements in glycaemic control with a low incidence of hypoglycaemia , weight gain or other adverse effects .
CONCLUSIONS	These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycaemia may be effectively managed with oral , non-insulin therapy .

