sitagliptin-phosphate and Osteoporotic-Fractures

To examine fracture incidence among participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).. We used data from 14 671 participants in the TECOS study who were randomized double-blind to sitagliptin (n = 7332) or placebo (n = 7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment was examined using multivariable Cox proportional hazards regression.. The baseline mean (standard deviation) participant age was 65.5 (8.0) years, diabetes duration was 11.6 (8.1) years and glycated haemoglobin level was 7.2 (0.5)% [55.2 (5.5) mmol/mol], and 29.3% of participants were women and 32.1% were non-white. During 43 222 person-years' follow-up, 375 (2.6%; 8.7 per 1000 person-years) had a fracture; 146 were major osteoporotic fractures (hip, n = 34; upper extremity, n = 81; and clinical spine, n = 31). Adjusted analyses showed fracture risk increased independently with older age (P < .001), female sex (P < .001), white race (P < .001), lower diastolic blood pressure (P < .001) and diabetic neuropathy (P = .003). Sitagliptin, compared with placebo, was not associated with a higher fracture risk [189 vs 186 incident fractures: unadjusted hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.82 to 1.23, P = .944; adjusted HR 1.03, P = .745], major osteoporotic fractures (P = .673) or hip fractures (P = .761). Insulin therapy was associated with a higher fracture risk (HR 1.40, 95% CI 1.02-1.91; P = .035), and metformin with a lower risk (HR 0.76, 95% CI 0.59-0.98; P = .035).. Fractures were common among people with diabetes in the TECOS study, but were not related to sitagliptin therapy. Insulin and metformin treatment were associated with higher and lower fracture risks, respectively.

Topics: Age Factors; Aged; Blood Preservation; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Therapy, Combination; Female; Fractures, Bone; Glycated Hemoglobin; Hip Fractures; Humans; Hypoglycemic Agents; Incidence; Insulin; Male; Metformin; Middle Aged; Osteoporotic Fractures; Proportional Hazards Models; Risk Factors; Sex Factors; Sitagliptin Phosphate; White People

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).. To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study.. 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.. 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.. 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.. 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.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Male; Middle Aged; Osteoporotic Fractures; Risk Assessment; Risk Factors; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones