NCT01055223

Fracture Risk With Thiazolidinediones

The Association Between Exposure to Spironolactone or Amiloride and Fracture Risk Among Subjects Treated With Thiazolidinediones

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 98,483 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

Conditions

• Fractures, Bone
• Type II Diabetes

Interventions

Type	Name	Description
DRUG	TZD only (RSG or PIO or troglitazone)	Drug exposure will be inferred from prescription claims. Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion.
DRUG	TZD + spironolactone	Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion. In order to be eligible for inclusion in this category, the prescription days supply for TZD and spirinolactone must overlap by at least 30 days.
DRUG	TZD + amiloride	Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion. In order to be eligible for inclusion in this category, the prescription days supply for TZD and Amiloride must overlap by at least 30 days.

Timeline

• Start date: 2009-05-01
• Primary completion: 2010-03-01
• Completion: 2010-03-01
• First posted: 2010-01-25
• Last updated: 2017-05-30
• Results posted: 2011-04-18