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

Diabet Med. 2005 Apr;22(4):374-81. doi: 10.1111/j.1464-5491.2005.01511.x.

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 A1c (A1c), 2-h post-prandial blood glucose (BG), hypoglycaemia rate (episodes/patient/30 days), incidence (% patients experiencing > or = 1 episode) of overall and nocturnal hypoglycaemia.

Results: At endpoint, A1c 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 A1c 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 A1c, 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • Circadian Rhythm
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Delivery Systems
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / adverse effects
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use*
  • Insulin Glargine
  • Insulin Lispro
  • Insulin, Long-Acting
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Weight Gain / drug effects

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • Insulin, Long-Acting
  • Insulin Glargine
  • Metformin