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

Annals of Internal Medicine, 05/25/2011

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.


  • MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases.
  • 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.
  • Primary end points were change in HbA1c level, change in weight, and frequency of severe hypoglycemia.


  • 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 glucagon–like 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.

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