An analysis of early insulin glargine added to metformin with or without sulfonylurea: impact on glycaemic control and hypoglycaemia

Diabetes Obes Metab. 2011 Sep;13(9):814-22. doi: 10.1111/j.1463-1326.2011.01412.x.


Aim: To evaluate the benefits of initiating insulin at an earlier versus later treatment stage, and regimens with/without sulfonylurea (SU).

Methods: Pooled analysis of 11 prospective randomized clinical trials, including 2171 adults with uncontrolled type 2 diabetes initiating insulin glargine following a specific titration algorithm. Clinical outcomes were glycated haemoglobin A1c (HbA1c) reduction, per cent achieving HbA1c ≤ 7.0%, weight gain and hypoglycaemic events. Statistical analysis compared outcomes 24 weeks after basal insulin initiation in patients previously uncontrolled on 0/1 oral antidiabetic drug (OAD) versus 2 OADs, and in patients taking metformin (MET) or SU alone or in combination at baseline. A meta-analysis was also conducted.

Results: For the pooled analysis, patients on 0/1 OAD and those on MET monotherapy at baseline had the largest 24-week reductions in HbA1c following the addition of insulin glargine (∼0.44 U/kg). Of patients failing MET/SU monotherapy and MET + SU in combination, 68.1, 50.4 and 56.4% achieved HbA1c ≤ 7.0%, respectively (p = 0.0006). Weight gain was lowest when basal insulin was added to MET. Patients on 0/1 OAD at baseline had significantly less symptomatic hypoglycaemia when basal insulin was added than those on 2 OADs (p = 0.0007). Despite higher insulin doses, those taking MET alone had less hypoglycaemia than those taking SU or MET + SU. Results were confirmed in the meta-analysis.

Conclusion: Adding insulin glargine to MET monotherapy early in treatment may provide efficacy/safety benefits over regimens including SU. This may reflect treatment earlier in the disease and supports the inclusion of insulin as a second step in the American Diabetes Association/European Association for the Study of Diabetes treatment algorithm.

Publication types

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

MeSH terms

  • Algorithms
  • Blood Glucose / drug effects*
  • Blood Glucose / physiology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / drug effects*
  • Glycated Hemoglobin A / physiology
  • Humans
  • Hypoglycemia / drug therapy*
  • Hypoglycemia / physiopathology
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives*
  • Insulin / pharmacology
  • Insulin Glargine
  • Insulin, Long-Acting
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacology
  • Middle Aged
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Sulfonylurea Compounds / administration & dosage*
  • Sulfonylurea Compounds / pharmacology
  • Treatment Outcome


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