Relationship between HbA1c and hypoglycaemia in patients with type 2 diabetes treated with different insulin regimens in combination with metformin

Diabetes Metab Res Rev. 2009 Mar;25(3):224-31. doi: 10.1002/dmrr.929.


Background: To examine the relationship between glycaemic control and hypoglycaemia in patients with type 2 diabetes treated with metformin (Met) and either insulin lispro mixtures, given twice or thrice daily (LM + Met), or insulin glargine, given once daily (G + Met).

Methods: Data from three randomized clinical trials were pooled to compare effects of LM + Met with G + Met.

Results: The LM + Met group achieved lower mean HbA(1c) (mean+/-SE, 7.2+/-0.1 vs. 7.7+/-0.1%, p<0.0001) and all meals combined post-prandial blood glucose (BG) (8.9+/-0.1 vs. 10.2+/-0.1 mmol/L, p<0.0001) compared with the G + Met group, but had higher fasting blood glucose (8.1+/-0.1 vs. 6.8+/-0.1 mmol/L, p<0.0001) and insulin requirement (0.7+/-0.01 vs. 0.6+/-0.01 U/kg, p<0.0001). Over the entire study period, daytime hypoglycaemia was higher for the LM + Met group (10.3 vs. 3.5 episodes/patient/year, p<0.0001) than for the G + Met group; however, nocturnal hypoglycaemia was lower (3.4 vs. 6.6 episodes/patient/year, p=0.003). At endpoint, daytime hypoglycaemia was higher for the LM + Met group (6.2 vs. 1.4 episodes/patient/year, p<0.0001); however, nocturnal hypoglycaemia was similar in both groups (1.9 vs. 3.0 episodes/patient/year). An inverse relationship was observed between all confirmed hypoglycaemia and HbA(1c) at endpoint; for every 1% reduction in HbA(1c), the increase (in slope) was 1.4 episodes/patient/year (p=0.04). Patients with confirmed hypoglycaemia had lower HbA(1c) than patients without hypoglycaemia (7.39 vs. 7.64%, respectively; decrement=0.26%, p=0.026).

Conclusions: These studies demonstrated an inverse relationship between HbA(1c) and 24-h and daytime hypoglycaemia. Lispro insulin mixtures provided lower HbA(1c) and post-prandial blood glucose values than glargine, but caused more daytime hypoglycaemia. Frequency of nocturnal hypoglycaemia was similar and severe hypoglycaemia was rare with both insulin regimens.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Fasting / blood
  • Female
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Hypoglycemia / blood*
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives*
  • Insulin Glargine
  • Insulin Lispro
  • Insulin, Long-Acting
  • Male
  • Metformin / administration & dosage*
  • Middle Aged


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