TITLE

Effect of Antihyperglycemic Agents Added to Metformin and a Sulfonylurea on Glycemic Control and Weight Gain in Type 2 Diabetes: A Network Meta-analysis

AUTHOR(S)
Gross, Jorge L.; Kramer, Caroline K.; Leitão, Cristiane B.; Hawkins, Neil; Viana, Luciana V.; Schaan, Beatriz D.; Pinto, Lana C.; Rodrigues, Ticiana C.; Azevedo, Mirela J.
PUB. DATE
May 2011
SOURCE
Annals of Internal Medicine;5/17/2011, Vol. 154 Issue 10, p672
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea. Purpose: To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea. Data Sources: MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases. Study Selection: Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A1c (HbA1c) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea. Data Extraction: Primary end points were change in HbA1c level, change in weight, and frequency of severe hypoglycemia. Data Synthesis: Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA1c level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagonlike peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents. Limitations: Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions. Conclusion: There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patient's clinical characteristics. Primary Funding Source: Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
ACCESSION #
60796046

 

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