Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 5; pp. 1963 - 1969
• Main Authors: Majumdar, Sumit R, Josse, Robert G, Lin, Mu, Eurich, Dean T
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.05.2016; Copyright by The Endocrine Society
• Subjects: Aged; Diabetes Mellitus, Type 2 - drug therapy; Female; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Incidence; Insulin - adverse effects; Insulin - therapeutic use; Male; Middle Aged; Original; Osteoporotic Fractures - epidemiology; Osteoporotic Fractures - etiology; Risk Assessment; Risk Factors; Sitagliptin Phosphate - adverse effects; Sitagliptin Phosphate - therapeutic use; Sulfonylurea Compounds - adverse effects; Sulfonylurea Compounds - therapeutic use; Thiazolidinediones - adverse effects; Thiazolidinediones - therapeutic use
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2015-4180

Context: Type 2 diabetes and osteoporosis are both common, chronic, and increase with age, whereas type 2 diabetes is also a risk factor for major osteoporotic fractures (MOFs). However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin). Objective: To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study. Design, Setting, and Subjects: A sitagliptin new user study design employing a nationally representative Unites States claims database of 72 738 insured patients with type 2 diabetes. We used 90-day time-varying sitagliptin exposure windows and controlled confounding by using multivariable analyses that adjusted for clinical data, comorbidities, and time-updated propensity scores. Main Outcomes: We compared the incidence of MOF (hip, clinical spine, proximal humerus, distal radius) in new users of sitagliptin vs nonusers over a median 2.2 years follow-up. Results: At baseline, the median age was 52 years, 54% were men, and median A1c was 7.5%. There were 8894 new users of sitagliptin and 63 834 nonusers with a total 181 139 person-years of follow-up. There were 741 MOF (79 hip fractures), with 53 fractures (4.8 per 1000 person-years) among new users of sitagliptin vs 688 fractures (4.0 per 1000 person-years) among nonusers (P = .3 for difference). In multivariable analyses, sitagliptin was not associated with fracture (adjusted hazard ratio 1.1, 95% confidence interval 0.8–1.4; P = .7), although insulin (P < .001), sulfonylureas (P < .008), and thiazolidinedione (P = .019) were each independently associated with increased fracture risk. Conclusions: Even in a young population with type 2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type 2 diabetes were associated with increased risk. These data should be considered when making treatment decisions for those with type 2 diabetes at particularly high risk of fractures. Even in a young population with type-2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type-2 diabetes were associated with increased risk.