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February 12, 1996

Efficacy of Insulin and Sulfonylurea Combination Therapy in Type II Diabetes: A Meta-analysis of the Randomized Placebo-Controlled Trials

Author Affiliations

From the Carl T. Hayden Veterans Affairs Medical Center and the University of Arizona School of Medicine, Tucson.

Arch Intern Med. 1996;156(3):259-264. doi:10.1001/archinte.1996.00440030049007

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.(Arch Intern Med. 1996;156:259-264)

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