SGLT2 Inhibitors and the Risk of Hospitalization for Fournier's Gangrene: A Nested Case-Control Study.

Introduction: Based on post-marketing surveillance, concern has been raised that sodium-glucose cotransporter 2 inhibitors (SGLT2i) may increase the risk of necrotizing fasciitis of the perineum (Fournier's gangrene, FG). As a result of the low incidence of FG, data from clinical trials may be insufficient to robustly assess this issue because of the relatively limited numbers of participants. Real-world evidence may help clarify the association between SGLT2i and FG in the type 2 diabetes (T2D) population.

Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients.

Background: Some patients with chronic kidney disease do not respond adequately to erythropoiesis-stimulating agent (ESA) treatment; these patients are referred to as ESA hyporesponders. There is no widely accepted contemporary definition for chronic ESA hyporesponse. The study objective was to propose and validate an operational definition for chronic ESA hyporesponse.

Incretin-mimetic therapies and pancreatic disease: a review of observational data.

Background/objective: Signals from the FDA Adverse Event Reporting System (AERS) and pre-clinical and human pancreata obtained from organ donors have suggested that incretin-based therapies used to treat type 2 diabetes mellitus, such as glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, may increase the risk of acute pancreatitis (AP) and pancreatic cancer (PC). However, data from observational studies and randomized trials have been conflicting. We conducted a literature review to identify and summarize all observational data published assessing the pancreatic safety of incretins.

Meta-analysis of clinical trial safety data in a drug development program: answers to frequently asked questions.

Background: Meta-analyses of clinical trial safety data have risen in importance beyond regulatory submissions. During drug development, sponsors need to recognize safety signals early and adjust the development program accordingly, so as to facilitate the assessment of causality. Once a product is marketed, sponsors add postapproval clinical trial data to the body of information to help understand existing safety concerns or those that arise from other postapproval data sources, such as spontaneous reports.

An assessment of the association between carvedilol exposure and severe hypersensitivity reactions, angioedema, and anaphylactic reactions: a retrospective nested case-control analysis.

Background: There is limited information in the literature regarding the risk of severe hypersensitivity reactions due to different β-blocking agents. Most of the available information addresses the potential for increased severity of anaphylaxis or poor response to treatments among patients receiving β-blocking agents.

Objective: The objective of this study was to estimate the incidence rates of severe hypersensitivity reactions (angioedema and anaphylactic reactions) for various β-blockers and to examine the risk of severe hypersensitivity reactions in patients exposed to carvedilol extended-release compared with carvedilol and compared with other β-blockers.

Antidiabetic medication use and prevalence of chronic kidney disease among patients with type 2 diabetes mellitus in the United States.

Objectives: The aims of this study were to estimate the proportion of patients with type 2 diabetes mellitus (DM) in the United States with different stages of chronic kidney disease (CKD) and to describe glycemic control and antidiabetic drug use among them.

Methods: Using data from the Fourth National Health and Nutrition Examination Survey (NHANES IV) for the years 1999 through 2004, we performed a cross-sectional analysis of patients with type 2 DM aged >or=20 years at the time of the survey interview. CKD stages were categorized according to the classification system established by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative.

An assessment of the effect of thiazolidinedione exposure on the risk of myocardial infarction in type 2 diabetic patients.

Purpose: To determine the likelihood of myocardial infarction (MI) in type 2 diabetic patients exposed to rosiglitazone and pioglitazone, separately, compared to other antidiabetic therapies.

Methods: A case-control analysis nested within the cohort of type 2 diabetic subjects from the Integrated Healthcare Information Services (IHCIS) claims database. Incident cases of MI were matched to three controls each on age (+/-5 years), gender, and year of first diabetes diagnosis.

The incidence of heart failure among nondiabetic patients with and without impaired fasting glucose.

Objective: The purpose of this study was to elucidate the relationship between fasting plasma glucose (FPG), development of diabetes, and incident heart failure (HF) in a large, community sample of nondiabetic subjects.

Research Design And Methods: From Kaiser Permanente Northwest medical records, we identified 10,113 subjects with an FPG level of 100-125 mg/dl in 1997 or 1998 who were free of diabetes and HF and matched them to an equal number of subjects with an FPG level of <100 mg/dl on sex and 5-year age groups. Subjects were followed until a new diagnosis of HF was entered into the medical record, death, termination of health plan membership, or December 31, 2005, whichever came first.

The risk of myopathy associated with thiazolidinediones and statins in patients with type 2 diabetes: a nested case-control analysis.

Background: The implementation of more aggressive goals for low-density lipoprotein cholesterol lowering in subjects with type 2 diabetes (T2D) and the expected increase in the use of statins is likely to increase the concomitant use of thiazolidinediones (TZDs) and statins.

Objective: This study evaluated whether concomitant use of TZDs and statins is associated with an increased risk of myopathic events in subjects with T2D.

Methods: This was a nested case-control study in subjects with T2D.

Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000-2007.

Background: The risk of coronary heart disease (CHD) in users of antidiabetic agents must be quantified to permit reasoned therapeutic choices.

Objectives: To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas.

Methods: We conducted a retrospective cohort study of MI and CR in the PharMetrics database.

Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and nondiabetic patients.

Background: Estimates of myopathy rates in the literature are based on adverse events reported in clinical trials, which may not be representative of the clinical practice setting.

Objective: The objective of this study was to estimate the prevalence of myopathic events, particularly myalgia, myositis, and rhabdomyolysis in a community-based practice among a cohort of subjects with or without diabetes, some of whom received statin treatment.

Methods: In this retrospective data analysis, we identified members of a health maintenance organization (HMO) who initiated statin treatment between 1997 and 2004 and classified them into 2 groups: those subjects with diabetes and those without.

The risk of coronary heart disease in type 2 diabetic patients exposed to thiazolidinediones compared to metformin and sulfonylurea therapy.

Purpose: To evaluate whether the risk of coronary heart disease (CHD) differs among adult diabetic patients treated with thiazolidinediones (TZDs) and similar patients treated with combined oral metformin and sulfonylurea (M + S) therapy.

Methods: We conducted a retrospective cohort study involving 25 140 diabetic patients aged 18 and older who had at least one pharmacy claim for a TZD or combined M + S therapy between 1 January 1999 and 30 June 2002. We used propensity score matching to adjust for observable differences between initiators of combined M + S therapy and TZD initiators.

The association between fibrate use, change in high-density lipoprotein cholesterol, and the risk of cardiovascular disease: a retrospective chart review involving up to 8 years of follow-up.

Background: Clinical trials have indicated that the use of fibric acid derivatives confers a benefit against cardiovascular disease (CVD) in selected populations. However, whether fibrates provide a CVD risk reduction independent of changes in the traditional lipoprotein fractions and other known CVD risk factors is not clear.

Objective: This study examined whether the use of fibrate therapy in a general clinical setting provided cardiovascular benefits independent of changes in the traditional lipoprotein fractions.

The independent correlation between high-density lipoprotein cholesterol and subsequent major adverse coronary events.

Background: There is substantial evidence from clinical trials that lowering low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular risk. There is less evidence for the salutatory effects of raising high-density lipoprotein cholesterol (HDL-C). The predictive strength of an initial HDL-C measurement and its change over time for major adverse coronary events is not well understood.

The metabolic syndrome and schizophrenia: a review.

The clinical phenomenon described as the metabolic syndrome has received considerable attention both in the recent medical literature and popular press. Many of the sequelae of events attributable to newer atypical antipsychotics are consistent with the metabolic syndrome definition. This article describes and summarizes the information available on metabolic syndrome in the mental illness disease area and the proposed mechanisms for the increased prevalence of the metabolic syndrome in this population.

Atypical antipsychotic therapy and hyperlipidemia: a review.

Ziprasidone (Geodon), risperidone (Risperdal), and aripiprazole (Abilify) appear to be associated with a relatively low risk for hyperlipidemia, whereas quetiapine (Seroquel), olanzapine (Zyprexa), and clozapine (Clozaril) are associated with a relatively high risk for hyperlipidemia. Possible underlying causes of lipid dysregulation include weight gain, dietary changes, and glucose intolerance. Given the multiple cardiovascular risk factors reported for patients with schizophrenia, great care must be exercised to minimize the additional risk for hyperlipidemia when choosing antipsychotic therapy.

Antidiabetic therapy and the risk of heart failure in type 2 diabetic patients: an independent effect or confounding by indication.

Purpose: This study assesses the effect of the type of antidiabetic treatment on the risk of developing congestive heart failure (CHF) in type 2 diabetes.

Methods: The study was derived from the U.K.

Major CHD risk factors predominate among African-American women who are eligible for lipid-lowering drug therapy under the new ATP III guidelines.

Background: Coronary heart disease remains the leading cause of morbidity and death among African-Americans. We studied the cardiovascular risk factor distributions among African-American men and women deemed eligible for lipid-lowering treatment under the new Adult Treatment Panel Guidelines (ATPIII).

Design And Methods: A sub-sample of African-American NHANES III subjects aged 20-79 years, with known cardiovascular risk factors and LDL-C levels was identified (n=4,213).

The incidence of congestive heart failure associated with antidiabetic therapies.

Background: Increased risk for CHF in persons with type 2 diabetes is well established. Our objectives were to estimate the CHF risk associated with specific therapies for diabetes and to determine the differences in incidence rates of CHF associated with adding various antidiabetic agents.

Methods: Subjects were members of the Kaiser Permanente Northwest (KPNW) diabetes registry as of 1 January 1998, with no prior history of CHF (n = 8063).

The incidence of congestive heart failure in type 2 diabetes: an update.

Objective: The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up.

Research Design And Methods: We performed a retrospective cohort study of 8,231 patients with type 2 diabetes and 8,845 nondiabetic patients of similar age and sex who did not have CHF as of 1 January 1997, following them for up to 72 months to estimate the CHF incidence rate. In the diabetic cohort, we constructed a Cox regression model to identify risk factors for CHF development.

The effects of antipsychotic therapy on serum lipids: a comprehensive review.

Objectives: The purpose of this paper is to review the literature since 1970 documenting the effects of antipsychotic agents on serum lipids, including a discussion of possible mechanisms for the observed phenomena, the clinical significance and recommendations for monitoring hyperlipidemia during antipsychotic therapy.

Results: High-potency conventional antipsychotics (e.g.

Glycemic control from 1988 to 2000 among U.S. adults diagnosed with type 2 diabetes: a preliminary report.

Objective: To describe the changes in demographics, antidiabetic treatment, and glycemic control among the prevalent U.S. adult diagnosed type 2 diabetes population between the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and the initial release of NHANES 1999-2000.