Conclusion
Our review found that, compared with metformin, second- and third-generation sulfonylureas may not affect all-cause or cardiovascular mortality but may decrease the risk of nonfatal macrovascular outcomes among patients with type 2 diabetes. These agents may also increase the risk of hypoglycemia. However, the available data were too few and inconsistent to provide firm evidence concerning patient-important outcomes.
The most widely used guidelines recommend metformin as a first-line antidiabetic drug.1,52,53 This recommendation may be influenced by the results of the UKPDS trial for the subgroup of overweight and obese participants. However, this trial was of limited size and possibly biased in its reporting of the comparison of sulfonylurea and metformin, because it apparently did not adhere to the predefined statistical analysis plan described in the design article. Additional factors, such as sulfonylurea’s likely association with weight gain, as well as a number of potentially biased retrospective analyses, have all made sulfonylurea less used as monotherapy.2,39,54
Sulfonylurea is now largely prescribed as a part of a combination regimen.54 The use of sulfonylurea has to a large extent been replaced with the novel and, with respect to hard outcomes, as yet unproven but more expensive, dipeptidyl peptidase IV inhibitors.54 Future glucose-lowering interventions in type 2 diabetes need to be based on evidence from high-quality, long-term randomized clinical trials assessing patient-important outcomes.
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