The United Kingdom General Practice Research Database (GPRD) is an office-based, computer-generated, medical resource designed from its inception to be used for epidemiologic research. A distinct version of the GPRD is maintained by the Boston Collaborative Drug Surveillance Program and has been the source of more than 130 scientific articles primarily addressing drug safety issues. We reviewed evidence related to the validity of the GPRD. Specifically, with our extensive experience with this automated database, we evaluated the quality and completeness of the data that it contains.

OBJECTIVETo evaluate whether use of oral hypoglycemic agents is associated with an altered breast cancer risk in women.RESEARCH DESIGN AND METHODSUsing the U.K.-based General Practice Research Database, we conducted a nested case-control analysis among 22,621 female users of oral antidiabetes drugs with type 2 diabetes. We evaluated whether they had an altered risk of breast cancer in relation to use of various types of oral hypoglycemic agents. Case and control patients with a recorded diagnosis of type 2 diabetes were matched on age, calendar time, and general practice, and the multivariate conditional logistic regression analyses were further adjusted for use of oral antidiabetes drugs, insulin, estrogens, smoking BMI, diabetes duration, and HbA1c (A1C).RESULTSWe identified 305 case patients with a recorded incident diagnosis of breast cancer. The mean ± SD age was 67.5 ± 10.5 years at the time of the cancer diagnosis. Long-term use of ≥40 prescriptions (>5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24–0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer.CONCLUSIONSA decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis.

OBJECTIVE -Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs. RESEARCH DESIGN AND METHODS-This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time.RESULTS -Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23-3.50) compared with current metformin use.CONCLUSIONS -Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin.

Long-term use of sulfonylureas, thiazolidinediones, or insulin was not associated with an altered risk of developing AD. There was a suggestion of a slightly higher risk of AD in long-term users of metformin.

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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 casecontrol 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 antidia-betic 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.

Context Animal studies suggest that the ␤-blocker propranolol increases bone formation, but data on whether use of ␤-blockers (with or without concomitant use of thiazide diuretics) is associated with reduced fracture risk in humans are limited. Objective To determine whether use of ␤-blockers alone or in combination with thiazides is associated with a decreased risk of fracture in adults. Design, Setting, and Participants Case-control analysis using the UK General Practice Research Database (GPRD). The study included 30601 case patients aged 30 to 79 years with an incident fracture diagnosis between 1993 and 1999 and 120819 controls, matched to cases on age, sex, calendar time, and general practice attended. Main Outcome Measures Odds ratios (ORs) of having a fracture in association with use of ␤-blockers or a combination of ␤-blockers with thiazides. Results The most frequent fractures were of the hand/lower arm (n=12837 [42.0%]) and of the foot (n=4627 [15.1%]). Compared with patients who did not use either ␤-blockers or thiazide diuretics, the OR for current use of ␤-blockers only (Ն3 prescriptions) was 0.77 (95% confidence interval [CI], 0.72-0.83); for current use of thiazides only (Ն3 prescriptions), 0.80 (95% CI, 0.74-0.86); and for combined current use of ␤-blockers and thiazides, 0.71 (95% CI, 0.64-0.79). Data were adjusted for smoking; body mass index; number of practice visits; and use of calcium channel blockers, angiotensin-converting enzyme inhibitors, antipsychotics, antidepressants, statins, antiepileptics, benzodiazepines, corticosteroids, and estrogens. Conclusions Our data suggest that current use of ␤-blockers is associated with a reduced risk of fractures, taken alone as well as in combination with thiazide diuretics. Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with ␤-blockers and thiazides.

We quantified incidence rates and characteristics of patients with rosacea diagnosed in clinical practice in a large epidemiological study using primary care data from the U.K. Smoking was associated with a substantially reduced risk of developing rosacea.