Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia

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.Merck SA, Lyon, Franc

Use of depot medroxyprogesterone acetate and fracture risk

Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited.; We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk.; We conducted a case-control analysis using the United Kingdom-based General Practice Research Database.; Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008.; Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders.; We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (<2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1.; This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures

Mortality of patients with multiple sclerosis: a cohort study in UK primary care

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001–2006 and validated using patients’ original records where possible. We also included MS cases during 1993–2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4–2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46–2.38) vs. HR 1.31 (95 % CI 0.93–1.84), respectively. The most commonly recorded cause of death in MS patients was ‘MS’ (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients. Electronic supplementary material The online version of this article (doi:10.1007/s00415-014-7370-3) contains supplementary material, which is available to authorized users

The association between thyroid disorders and incident gout: population-based case-control study

Thyroid hormones influence kidney function and thereby might alter serum urate levels, a major risk factor for gouty arthritis.; To assess the risk of developing incident gout in association with hypothyroidism or hyperthyroidism.; Retrospective population-based case-control analysis.; UK-based Clinical Practice Research Datalink, a primary care research database.; We identified adult patients with a diagnosis of incident gout between 1990 and 2014. We matched one control to each gout case in terms of age, sex, general practice, calendar time, and years of active history in the database.; We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for developing gout in association with hypo- or hyperthyroidism and adjusted for potential confounders.; The study population encompassed 68,159 incident gout cases, of whom 78.8% were male, and the same number of matched controls. There was no increased risk of gout in patients with hypothyroidism: adjusted OR of gout of 1.12 (95% CI 1.05-1.20) compared with no hypothyroidism. Current short-term treatment of thyroid hormone replacement therapy was associated with an adjusted OR of gout of 1.54 (95% CI 1.24-1.92), compared with no treatment. Neither hyperthyroidism nor current treatment with thyroid suppression therapy was associated with gout (adjusted OR, 1.08 [95% CI 0.95-1.22] and 0.82 [95% CI 0.57-1.17], respectively).; This large observational study does not provide evidence that hypothyroidism or hyperthyroidism, irrespective of treatment, is associated with a clinically relevant increased risk of developing incident gout. There may be an exception among patients with newly diagnosed and treated hypothyroidism

Diabetes in Patients With Idiopathic Parkinson's Disease

OBJECTIVE—Previous observational studies reported inconsistent results on the association between diabetes and Parkinson's disease, and data on the risk of developing incident diabetes in relation to Parkinson's disease are scarce. We aimed at comparing the diabetes prevalence between patients with or without Parkinson's disease and at exploring the risk of developing incident diabetes associated with Parkinson's disease

Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database

Objective To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel

Częstość chorób wątroby u chorych na cukrzycę typu 2 leczonych doustnymi lekami przeciwcukrzycowymi

OBJECTIVE. We evaluated liver disease in conventionally treated type 2 diabetic patients to provide a reference against which reports of liver disease related to novel oral antidiabetic treatments could be compared. RESEARCH DESIGN AND METHODS. In this follow-up study, patients with type 2 diabetes who were treated with oral antidiabetic agents were identified from the U.K.-based General Practice Research Database and were followed to determine whether they developed liver disease. The specific types and etiologies of liver disorders were determined. Incidence rates were calculated based on the accumulated exposure time to oral antidiabetic agents. RESULTS. Among 44,406 type 2 diabetic patients, 605 had a computer diagnosis of liver disease with an incidence rate of 53.2/10,000 person-years (95% CI 49.2&#150;57.6). Of the 605 subjects, 186 had nonsympWSTĘP. W badaniu oceniane były przypadki uszkodzenia wątroby u chorych na cukrzycę typu 2 leczonych tradycyjnymi doustnymi środkami przeciwcukrzycowymi. Celem próby była ponowna analiza danych dotyczących zależności uszkodzeń wątroby od stosowania doustnych leków przeciwcukrzycowych. MATERIAŁ I METODY. Do badania zakwalifikowano chorych na cukrzycę typu 2 leczonych doustnymi lekami przeciwcukrzycowymi. Korzystano z Brytyjskiej Bazy Danych. Chorzy byli obserwowani w kierunku ewentualnego rozwoju chorób wątroby. Określono typ i etiologię rozpoznanych schorzeń, a ich częstość obliczano na podstawie skumulowanego czasu trwania terapii doustnej. WYNIKI. Spośród 44 406 chorych na cukrzycę typu 2 u 605 potwierdzono po przeprowadzeniu badania komputerowego występowanie choroby wątroby, wskaźnik zapadalności wynosił 53,2/10 000 osobolat (95% CI 49,2&#8211;57,6). U 186 z nich choroba miała postać łagodnych, przejściowych, bezobjawowych epizodów, u 249 występowały czynniki predysponujące, natomiast u 113 stwierdzono istnienie innych przyczyn uszkodzenia wątroby. Oceniono, że u 57 pacjentów uszkodzenie wątroby było prawdopodobnie spowodowane stosowaniem leków, wskaźnik zapadalności wynosił 5,0/10 000 osobolat (3,9&#8211;6,5). Rozpoznanie to potwierdzono w 11 przypadkach, u 8 chorych stwierdzono stłuszczenie wątroby spowodowane cukrzycą, u pozostałych chorych przyczyna pozostała nierozpoznana. Terapię doustnymi środkami przeciwcukrzycowymi kontynuowało 51 z 57 chorych, u 2 nie potwierdzono, że przyjmowane leki wywołały uszkodzenie wątroby, przy wskaźniku zapadalności wynoszącym 0,2/10 000 osobolat (< 0,1&#8211;0,6). WNIOSKI. W badanej populacji choroby wątroby występowały często. U wielu chorych dodatkowo występowały inne schorzenia, które mogą powodować uszkodzenie wątroby

Helping everyone do better: a call for validation studies of routinely recorded health data.

There has been a surge of availability and use for research of routinely collected electronic health data, such as electronic health records, health administrative data, and disease registries. Symptomatic of this surge, in 2012, Pharmacoepidemiology and Drug Safety (PDS) published a supplemental issue containing several reviews of validated methods for identifying health outcomes using routine health data,1 focusing on databases feeding the US Mini-Sentinel Program