Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A meta-analysis of the randomized placebo-controlled trials

Arch Intern Med. 1996 Feb 12;156(3):259-64.


Background: Numerous studies demonstrate the efficacy of the combination therapy of insulin and sulfonylurea in subjects with type II diabetes mellitus. However, two recent meta-analyses of randomized trials during the last decade provided inconsistent conclusions and failed to resolve the controversy.

Objective: To assess the efficacy of insulin and sulfonylurea combination therapy in type II diabetes mellitus by performing meta-analysis of only the controlled studies selected according to specific strict criteria.

Methods: A computerized literature survey was conducted using the MEDLINE database from January 1980 through March 1992 with the search headings of "sulfonylurea" and "insulin" and "combination therapy in diabetes mellitus. "A manual search was also performed using references from each retrieved report. Case reports, review articles, editorials, and citations reported in non-English-language journals without English translations were excluded. Forty-three citations were obtained. Four strict inclusion criteria were used to select studies: randomized, placebo-controlled trials (oral agent plus insulin vs placebo plus insulin); homogeneous target population (subjects with type II diabetes); intervention using the same sulfonylurea agent in a combination therapy; and uniform outcome measures to evaluate efficacy such as body weight; values for serum glucose, glycohemoglobin, and C peptide; daily insulin dosage; and lipid concentrations. More stringent qualitative subcriteria were then used to eliminate bias in the final unanimous selection by two blinded reviewers. Data were pooled and analyzed using Student's t test and Winer's combined test.

Results: Sixteen studies satisfied the inclusion criteria. Metabolic control improved with the combination therapy as reflected by a significant lowering of fasting serum glucose values (P < .01) and glycohemoglobin concentrations (P < .025). Moreover, improved metabolic control was achieved with a significantly smaller daily insulin dose (P < .01) and without a significant change in body weight. Finally, the combination therapy enhanced the endogenous insulin secretion as expressed by an increase in fasting serum C peptide concentration (P < .05).

Conclusions: Combination therapy with insulin and sulfonylurea may be a more appropriate and a suitable option to insulin monotherapy in subjects with non-insulin-dependent diabetes in whom primary or secondary failure to sulfonylurea developed. It may also be a more cost-effective way of long-term management in this group of subjects, especially in the elderly.

Publication types

  • Meta-Analysis

MeSH terms

  • Blood Glucose / metabolism
  • Body Weight
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / therapeutic use*
  • Male
  • Randomized Controlled Trials as Topic
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome


  • Blood Glucose
  • C-Peptide
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds