N/A
N=98,483
Fracture Risk With Thiazolidinediones
Fractures, Bone · Type II Diabetes
Bottom Line
View on ClinicalTrials.gov: NCT01055223 ↗Enrolled (actual)
98,483
Serious AEs
—
Results posted
Apr 2011
Primary outcome: Primary: Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD — 4325; 105; 12; 1 fractures
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- TZD only (RSG or PIO or troglitazone) (Drug); TZD + spironolactone (Drug); TZD + amiloride (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Mar 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD |
4325; 105; 12; 1; 17296; 292 | — |
| PRIMARY Number of Low Impact Fractures in Males and Females After 12 Months of Exposure to TZD |
2619; 64; 8; 0; 10496; 181 | — |
| SECONDARY Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 6 Months of Exposure to TZD |
2163; 48; 2; 1; 8615; 148 | — |
| SECONDARY Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 12 Months of Exposure to TZD |
1285; 29; 0; 0; 5115; 94 | — |
| SECONDARY Number of Hip Fractures Combined in Males and Females After 6 Months of Exposure to TZD |
92; 6; 387; 4 | — |
| SECONDARY Number of Hip Fractures Combined in Males and Females After 12 Months of Exposure to TZD |
44; 2; 182; 1 | — |
Summary
Treatment with thiazolidinediones (TZD) has recently been reported to possibly increase the risk of fractures in a randomized trial exploring the efficacy of rosiglitazone (RSG), metformin, or glyburide encompassing 4360 patients with type 2 diabetes.
It is hypothesized that spironolactone, a diuretic that is broadly used for the treatment of fluid retention and edema associated with TZD, has a potential protective effect against bone fractures. However, to our knowledge, this has not been tested in diabetic patients treated with TZD. Amiloride is another diuretic that shares with spironolactone the anti mineralocorticoid ion gated channels activity and will be analysed in this study with regard to possible protective effect against bone fracture in combination with TZD.
This study is a nested case-control study conducted among type 2 diabetes subjects exposed to TZD. The study aims to explore if the risk of fracture is reduced among type 2 diabetic subjects exposed to spironolactone and TZD. The study will compare the odds of any low impact fracture, and hand, foot, upper arm, wrist, and hip fracture incidence in subjects treated with TZD+spironolactone and TZD+amiloride compared to subjects treated with TZD only.
The study population will consist of type 2 diabetes patients aged 18 -65 years old exposed to TZD. To be eligible for the study, a subject must have had at least one International Classification of Disease (ICD)-9 code for type 2 diabetes and have at least 6 months or at least 12 months of exposure to TZD (rosiglitazone [RSG], pioglitazone [PIO] or troglitazone) during their follow-up time available in the database.
Eligibility Criteria
Inclusion Criteria
- At least one ICD-9 code for type 2 diabetes
- At least 6 months or at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database (The subject's study period begin date will be defined as the earliest date of their first TZD prescription. Subjects included in the study are required to have at least six months of follow-up time in the database prior to their first TZD prescription)
Exclusion Criteria
- Subjects with a diagnosis of Paget's disease and osteomalacia
- A history of fracture, osteoporosis or cancer prior to the first prescription of TZD (study begin date)
Data sourced from ClinicalTrials.gov (NCT01055223). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.