Meta-analysis of individual patient data to assess the risk of hypoglycaemia in people with type 2 diabetes using NPH insulin or insulin glargine

Diabetes Obes Metab. 2010 Sep;12(9):772-9. doi: 10.1111/j.1463-1326.2010.01232.x.


Aim: To estimate absolute and relative incidence rates of hypoglycaemia when using once-daily evening or morning regimens of insulin glargine (glargine) versus once-daily evening NPH insulin (NPH) using individual patient data (IPD).

Materials and methods: Randomized controlled trials with accessible IPD and including white European people with type 2 diabetes (T2DM) using glargine or NPH once-daily (with oral glucose-lowering drugs) were identified. Two study pools were analysed: evening glargine versus evening NPH (pool 1); and morning glargine versus evening NPH (pool 2). The number-needed-to-treat to avoid hypoglycaemia was calculated for glargine versus NPH.

Results: In study pool 1 (n = 2711), the risk of nocturnal hypoglycaemia was approximately halved with glargine compared with NPH [odds ratios (OR): 0.44-0.52, p < 0.001-0.047]. This led to a significant reduction in anytime risk of symptomatic hypoglycaemia [plasma glucose (PG) <3.9 mmol/l, OR: 0.64, p = 0.018; PG <2.0 mmol/l, OR: 0.51, p < 0.001]. In study pool 2 (n = 470), although a strong numerical reduction in all types of nocturnal hypoglycaemia was observed (OR: 0.16-0.64), statistical significance was reached only for symptomatic hypoglycaemia with PG <3.9 mmol/l (p < 0.001). Eight (pool 1) or five (pool 2) people with T2DM needed to use glargine rather than NPH to avoid one person from experiencing a nocturnal symptomatic hypoglycaemic event within a median of about 25 weeks of starting insulin.

Conclusions: This meta-analysis of open-label studies provides confidence that reductions of around 50% of risk for nocturnal hypoglycaemia can be achieved with using glargine instead of NPH.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / analogs & derivatives*
  • Insulin Glargine
  • Insulin, Isophane / administration & dosage
  • Insulin, Isophane / adverse effects*
  • Insulin, Long-Acting
  • Male
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Treatment Outcome


  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine
  • Insulin, Isophane