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.

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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.

Objective. To evaluate the association of glucocorticoids and other purported risk factors with the development of tuberculosis. Methods. We conducted a case-control study of tuberculosis cases identified during 1990 -2001 using the General Practice Research Database in the United Kingdom. Cases were patients with a first time diagnosis of tuberculosis accompanied by at least 6 months of treatment with at least 3 different tuberculosis medications. Up to 4 controls were matched to each case on age, sex, the practice attended by the case, index date, and amount of prior computerized records. Results. The study encompassed 497 new cases of tuberculosis and 1,966 controls derived from 16,629,041 person-years at risk (n ‫؍‬ 2,757,084 persons). The adjusted odds ratio (OR) of tuberculosis for current use of a glucocorticoid compared with no use was 4.9 (95% confidence interval [95% CI] 2.9 -8.3). The adjusted ORs for use of <15 mg and >15 mg of prednisone or its equivalent daily dose were 2.8 (95% CI 1.0 -7.9) and 7.7 (95% CI 2.8 -21.4), respectively. Adjusted ORs of tuberculosis were 2.8 for patients with a body mass index (BMI) <20 compared with normal BMI; 1.6 for current smokers compared with nonsmokers; and 3.8, 3.2, 2.0, and 1.4 for those with history of diabetes, emphysema, bronchitis, and asthma, respectively, compared with those without such history (all P values <0.05). Conclusion. These results indicate that patients treated with glucocorticoids have an increased risk of developing tuberculosis, independent of other risk factors. Low adiposity, diabetes, current smoking, and obstructive pulmonary disorders are also important independent risk factors for tuberculosis.

Risk factors for cardiovascular disease as well as myocardial infarction and other vascular diseases occur with higher incidence in patients with psoriasis than in the general population. Further work is needed to investigate whether these associations involve causal factors related to psoriasis or its treatment.

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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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.