Use of Thiazolidinediones and Fracture Risk

[Gatekeeper]

Use of Thiazolidinediones and Fracture Risk

Arch Intern Med. 2008;168( 8 ):820-825.

Background  Thiazolidinediones may adversely affect the skeleton owing to decreased bone formation and accelerated bone loss.

Methods   This study examines the association between the use of thiazolidinediones or other oral antidiabetic drugs and the risk of fracture. This nested case-control analysis uses the UK General Practice Research Database, including case patients with fracture aged 30 to 89 years with an incident fracture diagnosis between January 1994 and December 2005 and control subjects who were matched to case patients on age, sex, calendar time, and general practice attended. We assessed the odds ratios (ORs) of having a fracture associated with the use of rosiglitazone maleate, pioglitazone hydrochloride, other oral antidiabetic agents, or insulin.

Results   There were 1020 case patients with an incident low-trauma fracture and 3728 matched controls. After adjustment for age, body mass index, other antidiabetic drugs, comedication, and comorbidities, the ORs for users of 8 or more thiazolidinedione prescriptions (corresponding to approximately 12-18 months of therapy) compared with nonuse was 2.43 (95% confidence interval [CI], 1.49-3.95). Rosiglitazone (OR, 2.38; 95% CI, 1.39-4.09) and pioglitazone (OR, 2.59; 95% CI, 0.96-7.01) were used more frequently by case patients with fracture (predominantly hip and wrist fractures) than by controls. The association was independent of patient age and sex and tended to increase with thiazolidinedione dose. No materially altered relative fracture risk was found in association with the use of other oral antidiabetic drugs.

Conclusion  This analysis provides further evidence of a possible association between long-term use of thiazolidinediones and fractures, particularly of the hip and wrist, in patients with diabetes mellitus

rosiglitazone (Avandia, GlaxoSmithKline) or pioglitazone (Actos, Takeda)

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

[Gatekeeper]

Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial

The Lancet, Volume 373, Issue 9681, Pages 2125 - 2135, 20 June 2009

Background
Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the combination of the two over 5—7 years of follow-up. We also assessed comparative safety.

Methods
In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A1c (HbA1c) of 7·9% were randomly assigned to addition of rosiglitazone (n=2220) or to a combination of metformin and sulfonylurea (active control group, n=2227). The primary endpoint was cardiovascular hospitalisation or cardiovascular death, with a hazard ratio (HR) non-inferiority margin of 1·20. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00379769.

Findings
321 people in the rosiglitazone group and 323 in the active control group experienced the primary outcome during a mean 5·5-year follow-up, meeting the criterion of non-inferiority (HR 0·99, 95% CI 0·85—1·16). HR was 0·84 (0·59—1·18) for cardiovascular death, 1·14 (0·80—1·63) for myocardial infarction, and 0·72 (0·49—1·06) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 2·10, 1·35—3·27, risk difference per 1000 person-years 2·6, 1·1—4·1). Upper and distal lower limb fracture rates were increased mainly in women randomly assigned to rosiglitazone. Mean HbA1c was lower in the rosiglitazone group than in the control group at 5 years.

Interpretation
Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart failure and of some fractures, mainly in women. Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs.

Funding
GlaxoSmithKline plc, UK.