Trial Outcomes & Findings for Fracture Risk With Thiazolidinediones (NCT NCT01055223)

NCT ID: NCT01055223

Last Updated: 2017-05-30

Results Overview

ICD-9 codes (805-807.4x, 808-810.xx, 812-829.xx) were captured from Uniform Billing-92 records and Health Care Finance Administration records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription). For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.

Recruitment status

COMPLETED

Target enrollment

98483 participants

Primary outcome timeframe

From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 and December 31, 2008

Results posted on

2017-05-30

Participant Flow

Participant milestones

Participant milestones
Measure
TZD 6-month Cohort (Including TZD 12-month Cohort)
The study population consisted of type 2 diabetes patients 18-65 years old exposed to thiazolidinedione (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 of exposure to TZD (rosiglitazone \[RSG\], pioglitazone \[PIO\], or troglitazone) during their follow-up time available in the database. A subset of patients were followed for at least 12 months (Outcome measure results for this subset also presented). Dose information was not collected.
Overall Study
STARTED
98483
Overall Study
COMPLETED
98483
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Fracture Risk With Thiazolidinediones

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
TZD 6-month Cohort (Including TZD 12-month Cohort)
n=98483 Participants
The study population consisted of type 2 diabetes patients 18-65 years old exposed to thiazolidinedione (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 of exposure to TZD (rosiglitazone \[RSG\], pioglitazone \[PIO\], or troglitazone) during their follow-up time available in the database. A subset of patients were followed for at least 12 months (Outcome measure results for this subset also presented). Dose information was not collected.
Age, Continuous
52.2 Years
STANDARD_DEVIATION 8.33 • n=5 Participants
Sex: Female, Male
Female
37738 Participants
n=5 Participants
Sex: Female, Male
Male
60745 Participants
n=5 Participants

PRIMARY outcome

Timeframe: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 and December 31, 2008

Population: Type 2 diabetes patients 18-65 years old exposed to TZD. To be eligible for the study, a subject must have had at least one ICD-9 code for type 2 diabetes and have at least 6 months of exposure to TZD (RSG, PIO, or troglitazone) during their follow-up time available in the database.

ICD-9 codes (805-807.4x, 808-810.xx, 812-829.xx) were captured from Uniform Billing-92 records and Health Care Finance Administration records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription). For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.

Outcome measures

Outcome measures
Measure
TZD Alone
n=21621 Participants
Subjects with type 2 diabetes who had prescriptions for TZD only during their entire follow-up. Dose information was not collected.
TZD+Spironolactone
n=397 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and spironolactone during their entire follow-up. The prescription days supply for TZD and spirinolactone must overlap by at least 30 days. Dose information was not collected.
TZD+Amiloride
n=43 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and amiloride during their entire follow-up. The prescription days supply for TZD and amiloride must overlap by at least 30 days. Dose information was not collected.
Other
n=3 Participants
Subjects with type 2 diabetes with exposure to TZD, but did not fit into the TZD Alone, TZD+Spironolactone, or TZD+Amiloride treatment groups during their entire follow-up. The prescription days supply for TZD and other drugs must overlap by at least 30 days. Dose information was not collected.
Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD
Case
4325 fractures
105 fractures
12 fractures
1 fractures
Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD
Control
17296 fractures
292 fractures
31 fractures
2 fractures

PRIMARY outcome

Timeframe: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008

Population: The study population consisted 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 ICD-9 code for type 2 diabetes and have at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database.

ICD-9 codes (805-807.4x, 808-810.xx, 812-829.xx) were captured from Uniform Billing-92 records and Health Care Finance Administration records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription). For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.

Outcome measures

Outcome measures
Measure
TZD Alone
n=13115 Participants
Subjects with type 2 diabetes who had prescriptions for TZD only during their entire follow-up. Dose information was not collected.
TZD+Spironolactone
n=245 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and spironolactone during their entire follow-up. The prescription days supply for TZD and spirinolactone must overlap by at least 30 days. Dose information was not collected.
TZD+Amiloride
n=28 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and amiloride during their entire follow-up. The prescription days supply for TZD and amiloride must overlap by at least 30 days. Dose information was not collected.
Other
n=2 Participants
Subjects with type 2 diabetes with exposure to TZD, but did not fit into the TZD Alone, TZD+Spironolactone, or TZD+Amiloride treatment groups during their entire follow-up. The prescription days supply for TZD and other drugs must overlap by at least 30 days. Dose information was not collected.
Number of Low Impact Fractures in Males and Females After 12 Months of Exposure to TZD
Case
2619 fractures
64 fractures
8 fractures
0 fractures
Number of Low Impact Fractures in Males and Females After 12 Months of Exposure to TZD
Control
10496 fractures
181 fractures
20 fractures
2 fractures

SECONDARY outcome

Timeframe: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008

Population: The study population consisted 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 ICD-9 code for type 2 diabetes and have at least 6 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database.

ICD-9 codes (815.0x, 816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.

Outcome measures

Outcome measures
Measure
TZD Alone
n=10778 Participants
Subjects with type 2 diabetes who had prescriptions for TZD only during their entire follow-up. Dose information was not collected.
TZD+Spironolactone
n=196 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and spironolactone during their entire follow-up. The prescription days supply for TZD and spirinolactone must overlap by at least 30 days. Dose information was not collected.
TZD+Amiloride
n=20 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and amiloride during their entire follow-up. The prescription days supply for TZD and amiloride must overlap by at least 30 days. Dose information was not collected.
Other
n=3 Participants
Subjects with type 2 diabetes with exposure to TZD, but did not fit into the TZD Alone, TZD+Spironolactone, or TZD+Amiloride treatment groups during their entire follow-up. The prescription days supply for TZD and other drugs must overlap by at least 30 days. Dose information was not collected.
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 6 Months of Exposure to TZD
Case
2163 fractures
48 fractures
2 fractures
1 fractures
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 6 Months of Exposure to TZD
Control
8615 fractures
148 fractures
18 fractures
2 fractures

SECONDARY outcome

Timeframe: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008

Population: The study population consisted 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 ICD-9 code for type 2 diabetes and have at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database.

ICD-9 codes (815.0x, 816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.

Outcome measures

Outcome measures
Measure
TZD Alone
n=6400 Participants
Subjects with type 2 diabetes who had prescriptions for TZD only during their entire follow-up. Dose information was not collected.
TZD+Spironolactone
n=123 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and spironolactone during their entire follow-up. The prescription days supply for TZD and spirinolactone must overlap by at least 30 days. Dose information was not collected.
TZD+Amiloride
n=12 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and amiloride during their entire follow-up. The prescription days supply for TZD and amiloride must overlap by at least 30 days. Dose information was not collected.
Other
n=2 Participants
Subjects with type 2 diabetes with exposure to TZD, but did not fit into the TZD Alone, TZD+Spironolactone, or TZD+Amiloride treatment groups during their entire follow-up. The prescription days supply for TZD and other drugs must overlap by at least 30 days. Dose information was not collected.
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 12 Months of Exposure to TZD
Control
5115 fractures
94 fractures
12 fractures
2 fractures
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 12 Months of Exposure to TZD
Case
1285 fractures
29 fractures
0 fractures
0 fractures

SECONDARY outcome

Timeframe: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008

Population: The study population consisted 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 ICD-9 code for type 2 diabetes and have at least 6 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database.

ICD-9 codes (820.0x, 820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.

Outcome measures

Outcome measures
Measure
TZD Alone
n=479 Participants
Subjects with type 2 diabetes who had prescriptions for TZD only during their entire follow-up. Dose information was not collected.
TZD+Spironolactone
n=10 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and spironolactone during their entire follow-up. The prescription days supply for TZD and spirinolactone must overlap by at least 30 days. Dose information was not collected.
TZD+Amiloride
Subjects with type 2 diabetes who had prescriptions for TZD and amiloride during their entire follow-up. The prescription days supply for TZD and amiloride must overlap by at least 30 days. Dose information was not collected.
Other
Subjects with type 2 diabetes with exposure to TZD, but did not fit into the TZD Alone, TZD+Spironolactone, or TZD+Amiloride treatment groups during their entire follow-up. The prescription days supply for TZD and other drugs must overlap by at least 30 days. Dose information was not collected.
Number of Hip Fractures Combined in Males and Females After 6 Months of Exposure to TZD
Case
92 fractures
6 fractures
Number of Hip Fractures Combined in Males and Females After 6 Months of Exposure to TZD
Control
387 fractures
4 fractures

SECONDARY outcome

Timeframe: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008

Population: The study population consisted 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 ICD-9 code for type 2 diabetes and have at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database.

ICD-9 codes (820.0x, 820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records. Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription). For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.

Outcome measures

Outcome measures
Measure
TZD Alone
n=226 Participants
Subjects with type 2 diabetes who had prescriptions for TZD only during their entire follow-up. Dose information was not collected.
TZD+Spironolactone
n=3 Participants
Subjects with type 2 diabetes who had prescriptions for TZD and spironolactone during their entire follow-up. The prescription days supply for TZD and spirinolactone must overlap by at least 30 days. Dose information was not collected.
TZD+Amiloride
Subjects with type 2 diabetes who had prescriptions for TZD and amiloride during their entire follow-up. The prescription days supply for TZD and amiloride must overlap by at least 30 days. Dose information was not collected.
Other
Subjects with type 2 diabetes with exposure to TZD, but did not fit into the TZD Alone, TZD+Spironolactone, or TZD+Amiloride treatment groups during their entire follow-up. The prescription days supply for TZD and other drugs must overlap by at least 30 days. Dose information was not collected.
Number of Hip Fractures Combined in Males and Females After 12 Months of Exposure to TZD
Case
44 fractures
2 fractures
Number of Hip Fractures Combined in Males and Females After 12 Months of Exposure to TZD
Control
182 fractures
1 fractures

Adverse Events

TZD 6-month Cohort

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

TZD-12 Month Cohort

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

  • Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
  • Publication restrictions are in place

Restriction type: OTHER