Twice‐daily pre‐mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes

Abstract

Aims To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily in combination with metformin to that of once‐daily insulin glargine plus metformin in patients with Type 2 diabetes inadequately controlled with intermediate insulin, or insulin plus oral agent(s) combination therapy. Research design and methods Ninety‐seven patients were randomized in a multicentre, open‐label, 32‐week crossover study. Primary variables evaluated: haemoglobin A_1c (A_1c), 2‐h post‐prandial blood glucose (BG), hypoglycaemia rate (episodes/patient/30 days), incidence (% patients experiencing ≥ 1 episode) of overall and nocturnal hypoglycaemia. Results At endpoint, A_1c was lower with the insulin lispro mixture plus metformin compared with glargine plus metformin (7.54% ± 0.87% vs. 8.14% ± 1.03%, P < 0.001). Change in A_1c from baseline to endpoint was greater with the insulin lispro mixture plus metformin (−1.00% vs. −0.42%; P < 0.001). Two‐hour post‐prandial BG was lower after morning, midday, and evening meals (P < 0.001) during treatment with the insulin lispro mixture plus metformin. The fasting BG values were lower with glargine plus metformin (P = 0.007). Despite lower BG at 03.00 hours (P < 0.01), patients treated with the insulin lispro mixture plus metformin had a lower rate of nocturnal hypoglycaemia (0.14 ± 0.49 vs. 0.34 ± 0.85 episodes/patient/30 days; P = 0.002), although the overall hypoglycaemia rate was not different between treatments (0.61 ± 1.41 vs. 0.44 ± 1.07 episodes/patient/30 days; P = 0.477). Conclusion In patients with Type 2 diabetes and inadequate glucose control while on insulin or insulin and oral agent(s) combination therapy, treatment with a twice‐daily insulin lispro mixture plus metformin, which targets both post‐prandial and pre‐meal BG, provided clinically significant improvements in A_1c, significantly reduced post‐prandial BG after each meal, and reduced nocturnal hypoglycaemia as compared with once‐daily glargine plus metformin, a treatment that targets fasting BG.