Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs

H M Colhoun, S J Livingstone, H C Looker, A D Morris, S H Wild, R S Lindsay, C Reed, P T Donnan, B Guthrie, G P Leese, J McKnight, D W M Pearson, E Pearson, J R Petrie, Sam Philip, N Sattar, F M Sullivan, P McKeigue, Scottish Diabetes Research Network (SDRN) Epidemiology group

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Abstract

AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p¿=¿3¿×¿10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.
Original languageEnglish
Pages (from-to)2929-2937
Number of pages9
JournalDiabetologia
Volume55
Issue number11
Early online date4 Sep 2012
DOIs
Publication statusPublished - Nov 2012

Fingerprint

rosiglitazone
pioglitazone
Hip Fractures
Thiazolidinediones
Glucose
Pharmaceutical Preparations
Mortality
Metformin
Scotland
Urinary Bladder Neoplasms
Type 2 Diabetes Mellitus

Keywords

  • fractures
  • hip fracture
  • pharmacoepidemiolgy
  • thiazolidinedione
  • type 2 diabetes

Cite this

Colhoun, H. M., Livingstone, S. J., Looker, H. C., Morris, A. D., Wild, S. H., Lindsay, R. S., ... Scottish Diabetes Research Network (SDRN) Epidemiology group (2012). Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs. Diabetologia, 55(11), 2929-2937. https://doi.org/10.1007/s00125-012-2668-0

Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs. / Colhoun, H M; Livingstone, S J; Looker, H C; Morris, A D; Wild, S H; Lindsay, R S; Reed, C; Donnan, P T; Guthrie, B; Leese, G P; McKnight, J; Pearson, D W M; Pearson, E; Petrie, J R; Philip, Sam; Sattar, N; Sullivan, F M; McKeigue, P; Scottish Diabetes Research Network (SDRN) Epidemiology group.

In: Diabetologia, Vol. 55, No. 11, 11.2012, p. 2929-2937.

Research output: Contribution to journalArticle

Colhoun, HM, Livingstone, SJ, Looker, HC, Morris, AD, Wild, SH, Lindsay, RS, Reed, C, Donnan, PT, Guthrie, B, Leese, GP, McKnight, J, Pearson, DWM, Pearson, E, Petrie, JR, Philip, S, Sattar, N, Sullivan, FM, McKeigue, P & Scottish Diabetes Research Network (SDRN) Epidemiology group 2012, 'Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs', Diabetologia, vol. 55, no. 11, pp. 2929-2937. https://doi.org/10.1007/s00125-012-2668-0
Colhoun, H M ; Livingstone, S J ; Looker, H C ; Morris, A D ; Wild, S H ; Lindsay, R S ; Reed, C ; Donnan, P T ; Guthrie, B ; Leese, G P ; McKnight, J ; Pearson, D W M ; Pearson, E ; Petrie, J R ; Philip, Sam ; Sattar, N ; Sullivan, F M ; McKeigue, P ; Scottish Diabetes Research Network (SDRN) Epidemiology group. / Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs. In: Diabetologia. 2012 ; Vol. 55, No. 11. pp. 2929-2937.
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abstract = "AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95{\%} CI 1.09, 1.28; p¿=¿3¿×¿10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95{\%} CI 1.03, 1.41) and women (OR 1.18; 95{\%} CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15{\%}) and in never-users (13{\%}). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.",
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AU - Looker, H C

AU - Morris, A D

AU - Wild, S H

AU - Lindsay, R S

AU - Reed, C

AU - Donnan, P T

AU - Guthrie, B

AU - Leese, G P

AU - McKnight, J

AU - Pearson, D W M

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AU - Petrie, J R

AU - Philip, Sam

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AU - Sullivan, F M

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N2 - AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p¿=¿3¿×¿10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

AB - AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p¿=¿3¿×¿10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

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KW - type 2 diabetes

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DO - 10.1007/s00125-012-2668-0

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JO - Diabetologia

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