Sulfonylureas increase the secretion of insulin from pancreatic beta cells, significantly lower blood glucose, and reduce A1C levels by 1% to 2%.6 Because hypoglycemia is a serious risk with sulfonylureas, they should be used conservatively in the elderly.2 Avoid using sulfonylurea formulations with long half-lives or active metabolites, which can cause severe and prolonged hypoglycemia.8,9
Glyburide is broken down into active metabolites that accumulate in patients who have renal insufficiency; it should be avoided in older adults due to the risk of life-threatening hypoglycemic events.10 Glipizide has no active metabolites and has the lowest risk of hypoglycemia in the setting of decreased renal function, making it the preferred sulfonylurea for use in the elderly.3,10
Thiazolidinediones (TZDs) reduce insulin resistance and decrease hepatic glucose production without increasing the risk of hypoglycemia. These agents effectively lower A1C levels by 1% to 1.5%.11 Despite their efficacy, TZDs have limited benefit because of adverse effects. Serious complications include fluid retention that can exacerbate or lead to worsening heart failure, weight gain, macular edema, and hepatic failure.
Specifically, with pioglitazone, there is also a slightly increased risk of bladder cancer.2 In one study involving more than 30,000 patients taking pioglitazone, an increase in bladder cancer was noted among those using the medication for more than 2 years.12 Still, the hazard ratio was only 1.2, with 90 cases diagnosed over the course of the study. A prudent strategy would be to avoid its use in those with high risk of developing bladder cancer. TZDs are contraindicated in patients with New York Heart Association class III or IV heart failure.8
Increased fracture risk has been identified in both men and women and is a concerning adverse effect in the elderly.8 Fracture risk with TZDs has been approximately twice that of placebo, noted in a study of older women where the fracture rate was 5.1% vs 2.5%, respectively.11 TZDs can be of value in lowering A1C levels without the risk of hypoglycemia. But, due to their adverse effect profile, use TZDs cautiously in older adults at risk for heart failure, falls, or fractures.3
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