Sulfonylureas and Risk of Falls and Fractures: A Systematic Review

Abstract

Sulfonylureas have been linked to increased risk of hypoglycemia. Hypoglycemia may lead to falls, and falls may lead to fracture. However, studies quantifying the association between sulfonylureas and fractures are sparse and yield inconsistent results. The purpose of this article was to review the literature regarding sulfonylurea use and falls or fall-related fractures among older adults with type 2 diabetes mellitus and to delineate areas for future research. We searched MEDLINE (1966-March 2012) and CINAHL (1937-March 2012) for studies of patients with type 2 diabetes mellitus living in the community or nursing homes. The search algorithms combined three domains: (1) diabetic patients, (2) sulfonylurea medications, and (3) fractures or falls. We included only publications in English that pertained to human subjects. We found 9 randomized trials and 12 non-experimental studies that met the inclusion criteria. The guidelines provided by the Cochrane handbook or Agency for Healthcare Research and Quality (AHRQ) Methods Guide are too general to distinguish the quality of included non-experimental studies, so we developed several specific domains based on those general guidelines. These domains included study design, study population, follow-up time, comparison group, exposure definition, outcome definition, induction period, confounding adjustment, and attrition or missing data. The data were not amenable to a meta-analysis. No clinical trials included fracture as a primary endpoint. Most clinical trials excluded older adults. Most studies were not designed to evaluate the risk of sulfonylureas on fractures or falls. Studies did not show an increased risk of falls/fractures with sulfonylurea. The data available from existing studies suffer from methodological limitations including insufficient events, lack of primary endpoints, exclusion of older adults, and lack of clarity or inappropriate comparison groups. Future studies are needed to appropriately estimate the effect of sulfonylureas on falls or fall-related fractures in older adults who are at increased risk for hypoglycemia, the hypothesized mechanism for fractures related to sulfonylurea therapy.