SULFONYLUREA USE AND RISK OF HIP FRACTURES AMONG ELDERLY MEN AND WOMEN WITH TYPE 2 DIABETES

Transcription

1 SULFONYLUREA USE AND RISK OF HIP FRACTURES AMONG ELDERLY MEN AND WOMEN WITH TYPE 2 DIABETES Swapnil N. Rajpathak 1, Chunmay Fu 1, Kimberly G. Brodovicz 1, Samuel S. Engel 1, Kate Lapane 2 1 Merck Sharp & Dohme Corp., Whitehouse Station, NJ 2 University of Massachusetts Medical School, Worcester, MA ISPOR, May 2013, New Orleans LA 1

2 SULFONYLUREA USE IN TYPE 2 DIABETES Sulfonylureas (SU) used to treat type 2 diabetes for over 50 years o 35% of patients use SU (monotherapy or combination with other drugs 1 ) Glipizide, glyburide, chlorpropamide, gliclazide, and glimepiride Mechanism of action: Stimulation of insulin secretion from pancreatic β-cells o Potent mechanism with high efficacy (HbA1c reduction) Common side effects hypoglycemia, weight gain o Hypoglycemia is common, and possibly related to other outcomes (CHD, falls/fractures) 2 and with high economic burden o Beer s criteria (AGS) for drug use in elderly 3 o Avoid use of glyburide and chlorpropamide 1 Dodd AH et al. Curr Med Res Opin Jul;25(7): Ginde et al. Diabetes Care 2008; 31; AGS Expert Panel. JAGS 2012 Apr;60(4):

3 HYPOGLYCEMIA, SU AND FRACTURES Fall-related fractures, especially that of hip, result in high morbidity and mortality in the elderly 1 Hypoglycemia and fracture risk Recent data suggest those with history of hypoglycemic events have greater risk of fall-related fractures; OR: 1.70 (95% CI: ) 2 Direct association between SU and fracture risk Recent Systematic Review 3 o Limited evidence o Existing studies limited by methodological issues: o Insufficient fracture events o Fracture not primary endpoint o Exclusion of elderly o Inappropriate comparisons 1 Barrett-Connor E. Am J Med 1995; 98: 2A 3S to 2A 8S. 2 Johnston et al. DOM ; Lapane K, Rajpathak S et al ; Drugs and Aging 2013 epub ahead of print

4 STUDY OBJECTIVE To evaluate the association between SU and risk of developing hip fracture among elderly patients with type 2 diabetes

5 METHODS Retrospective database study o Administrative insurance claims database for commercially-insured population (Ingenix /OptumInsight) o Information on demographics, patient clinical encounters, pharmaceutical dispensation, medical claims, etc. Study population o o Elderly men and women aged 65 years Type 2 diabetes (ICD xx) Study window period (Jan 2002-Dec 2005) o Index date: Jan 1, 2002 o Patients classified as SU users and non-users at baseline

6 Sample Selection Patients aged 65 years with type 2 diabetes (ICD-9 diagnosis) on oral anti-diabetic drug(s) on Jan 1, 2002 (n=144,867) EXCLUSIONS o Patients with <30 days drug supply (n = 29,327) o Patients using any insulin during study period (n=30,040) o Patients with no treatment changes after index date (n=42,645) o Patients with history of hip fracture at baseline (n=108) n = 42,747 SU Users n = 20,668 1:1 Propensity Score Matching* Non-SU Users n = 22,079 SU Users n = 13,189 Non-SU Users n = 13,189 *Age, gender, health insurance, region, CHD, stroke, osteoporosis, dementia, hypertension, and use of steroids, benzodiazepines, anti-depression, anti-psychotic, anti-convulsant therapy (Greedy technique) 6

7 METHODS Assessment of outcomes o Hip fracture (ICD xx) o Observation period (Jan 2002-Dec 2005) Secondary analysis: Association between diagnosed hypoglycemia and hip fracture risk o Hypoglycemia: ICD-9 (251.0, 250.2) and algorithm from Ginde et al 1 Multivariable conditional logistic regression analysis All data analyses were conducted using SAS ver Ginde et al. BMC Endocr Disord 8:4, 2008

8 Baseline Characteristics: SU users vs. non-users Characteristics SU Users Non Users P-value* (13,189) (13,189) Age, years 72.4 (6.2) 72.5 (6.4) 0.38 Women Co-morbid conditions CHD Stroke Osteoporosis <.0001 Dementia Hypertension Hypoglycemia** <.0001 Concomitant medication use Anti-depressants Benzodiazepines Antipsychotics Lipid lowering treatment Anti-convulsant therapy Opioids Steroids Numbers are Mean (SD) or Proportions (%) ; * paired t-test or chi-square test; **Not use d in PS calculation 8

9 Distribution of Sulfonylureas Drug N of Patients % Glyburide 6, Glipizide 5, Glimepiride 1, Others Others include Tolazamide, Tolbutamide, Acetohexamide, Chlorpropamide 9

10 Association Between SU use and Hip Fracture SU Users Non-SU ALL N =13,189 N =13,189 Hip fracture cases, N (%) Unadjusted PS matched conditional LR model OR % CI Multivariable PS matched conditional LR model* OR % CI MEN N = 7,122 N = 6,903 Hip fracture cases, N Multivariable PS adjusted unconditional LR model* OR % CI NA WOMEN N = 6,067 N = 6,286 Hip fracture cases, N Multivariable PS adjusted unconditional LR model* OR % CI NA *Adjusted for gender, dementia, osteoporosis, and use of anti-psychotic, anti-depressants, opioids, steroids and history of hypoglycemia. 10

11 Secondary Analysis: Diagnosed Hypoglycemia and Hip Fracture Diagnosed Hypoglycemia Yes No ALL N =1,036 N =25,342 Hip fracture cases, N Unadjusted model OR % CI Multivariable model* OR % CI Also adjusted for SU use OR % CI AMONG SU USERS N=688 N=12,501 Hip fracture cases, N Multivariable model* OR % CI All estimates based on unconditional LR ; *Adjusted for age, gender, region, dementia, history of hypoglycemia, osteoporosis, and use of anti-psychotic, anti-depressants, opioids and steroids. 11

12 LIMITATIONS Observational nature of the study o Residual confounding (measured or unmeasured) Relatively few cases of hip fractures Use of pharmacy claims database o Pharmacy claims do not confirm drug use o All events (drug fills, fractures, hypoglycemia) may not be captured o Possible incompleteness of data among elderly o Cannot directly relate the hip fracture to hypoglycemic episode Generalizability of the study

13 CONCLUSIONS SU use was associated with ~50% increased risk of hip fracture in elderly patients with type 2 diabetes Similar risk among men and women Patients with diagnosed hypoglycemia had higher risk of hip fractures These findings need to be confirmed in future studies To further investigate the interrelationships of SU, hypoglycemia, falls/fractures