Fracture Risk With Thiazolidinediones

NCT ID: NCT01055223

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 98483 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2010-03-31

Brief 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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Type 2 diabetes subjects

Type 2 diabetes subjects

TZD only (RSG or PIO or troglitazone)

Intervention Type: DRUG

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.

TZD + spironolactone

Intervention Type: DRUG

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.

TZD + amiloride

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Other Identifiers

113332

Identifier Type: -

Identifier Source: org_study_id