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

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

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

Diabetes, use of antidiabetic drugs, and the risk of glioma

Prior epidemiologic studies suggest inverse relations between diabetes and glioma risk, but the underlying mechanisms, including use of antidiabetic drugs, are unknown.; We therefore performed a matched case-control analysis using the Clinical Practice Research Datalink (CPRD). We identified incident glioma cases diagnosed between 1995 and 2012 and matched each case with 10 controls on age, gender, calendar time, general practice, and years of active history in the CPRD. We performed conditional logistic regression to estimate odds ratios (ORs) with 95% CIs, adjusted for body mass index and smoking.; We identified 2005 cases and 20 050 controls. Diabetes was associated with decreased risk of glioma (OR = 0.74; 95% CI = 0.60-0.93), particularly glioblastoma (OR = 0.69; 95% CI = 0.51-0.94). Glioblastoma risk reduction was markedly pronounced among diabetic men (OR = 0.60; 95% CI = 0.40-0.90), most apparently for those with diabetes of long-term duration (OR for &gt;5 vs 0 y = 0.46; 95% CI = 0.26-0.82) or poor glycemic control (OR for HbA1c ≥8 vs &lt;6.5% = 0.20; 95% CI = 0.06-0.70). In contrast, the effect of diabetes on glioblastoma risk was absent among women (OR = 0.85; 95% CI = 0.53-1.36). No significant associations with glioma were found for use of metformin (OR for ≥30 vs 0 prescriptions = 0.72; 95% CI = 0.38-1.39), sulfonylureas (OR = 0.71; 95% CI = 0.39-1.30), or insulin (OR = 0.79; 95% CI = 0.37-1.69).; Antidiabetic treatment appears to be unrelated to glioma, but long-term diabetes duration and increased HbA1c both show decreased glioma risk. Stronger findings in men than women suggest low androgen levels concurrent with diabetes as a biologic mechanism

Association of smoking with amyotrophic lateral sclerosis risk and survival in men and women: a prospective study

<p>Abstract</p> <p>Background</p> <p>Previous epidemiologic studies have examined the association of smoking with amyotrophic lateral sclerosis (ALS) incidence, but their results have been inconsistent. Moreover, limited information exists on the association between smoking and survival in ALS patients. We evaluated the association of smoking with ALS incidence and survival in a population-based cohort.</p> <p>Methods</p> <p>We conducted a case-control study nested in the General Practice Research Database, a computerized clinical database in the United Kingdom. Cases were 1143 individuals with a diagnosis of ALS; 11,371 matched controls were selected among GPRD participants free of ALS. Predictors of survival were determined in the ALS cases. Smoking information was obtained from the computer database.</p> <p>Results</p> <p>Smoking was not associated with the risk of ALS in this population. The rate ratio (RR) of ALS comparing ever versus never smokers was 1.04, 95% confidence interval (CI) 0.80-1.34. In analysis stratified by gender, however, ever smoking was associated with ALS in women (RR 1.53, 95% CI 1.04-2.23) but not in men (RR 0.75, 95% CI 0.53-1.06). Mortality was 71% after 2.1 average years of follow-up. Old age and female sex were associated with lower survival. Smoking was a predictor of mortality only in women. Comparing ever versus never smokers, RR (95% CI) of death was 1.31 (1.04-1.65) in women, and 0.90 (0.72-1.11) in men.</p> <p>Conclusion</p> <p>In this large population-based study, smoking was associated with ALS risk and worse survival in women but not in men.</p

Diabetes, use of metformin, and the risk of meningioma

Background Metformin is a commonly used oral antidiabetic agent that has been associated with decreased cancer risk. However, data regarding the association between metformin use and the risk of meningioma are unavailable. Methods We conducted a matched case-control analysis using data from the U. K.-based Clinical Practice Research Datalink (CPRD) to analyse diabetes status, duration of diabetes, glycemic control, and use of metformin, sulfonylureas, and insulin in relation to the risk of meningioma. We conducted conditional logistic regression analyses to determine relative risks, estimated as odds ratios (ORs) with 95% confidence intervals (CIs) and adjusted for body mass index, smoking, history of arterial hypertension, myocardial infarction, and use of estrogens (among women). Results We identified 2,027 meningioma cases and 20,269 controls. For diabetes there was the suggestion of an inverse association with meningioma (OR = 0.89; 95% CI = 0.74 - 1.07), which was driven by an inverse relation among women (OR = 0.78; 95% CI = 0.62 - 0.98), in whom we also noted a suggestive inverse association with duration of diabetes (p-value for trend = 0.071). For metformin there was a suggestive positive relation, particularly after matching on duration of diabetes and HbA1c level (OR = 1.64; 95% CI = 0.89 - 3.04). Sulfonylureas showed no clear association (OR = 0.91; 95% CI = 0.46 - 1.80). For insulin there was the suggestion of an inverse relation, in particular when comparing a high vs. low number of prescriptions (OR = 0.58; 95% CI = 0.18 - 1.83). Conclusion Further studies are needed to solidify a possible inverse association between diabetes and meningioma risk and to clarify the role of antidiabetics in this context