Diabetes frequently accompanies heart failure (HF) and HF is observed in up to 15% of patients with type 2 diabetes (T2D). The relationship between diabetes and the heart is, however, complex. It has long been known that diabetes is an important risk factor for coronary artery disease, resultant myocardial ischemia and infarctions leading to HF. But the direct effect of diabetes on the heart muscle is less clear.
The existence of a non-ischemic diabetic cardiomyopathy, disease of the cardiac muscle that is directly related to diabetes and not due to coronary atherosclerosis, has been a longstanding topic for debate. The recent EMPAREG-OUTCOME study in which patient assignment to the sodium-glucose co-transporter-2 (SGLT-2) inhibitor, empagliflozin, was associated with a reduction in HF hospitalizations by 35%1 (for unclear reasons) has reignited this discussion. Continue reading →
Both type 2 diabetes (T2D) and heart failure (HF) are on the rise and reaching epidemic proportions. This is no surprise as the two conditions are physiologically related. Both are associated with an aging population, dietary indiscretions and sedentary lifestyles. However, debate continues about whether or not an essential diabetic cardiomyopathy exists or if the HF frequently observed in diabetics is due to common comorbid conditions such as coronary artery disease or hypertension. In any case, the epidemiology of the two conditions runs in parallel. HF is currently the most frequent hospital discharge diagnosis provided in US patients over the age of 65 and the prevalence of T2D is about 25% in this age group.
Diabetic kidney disease (DKD) patients have an increased cardiovascular (CV) risk in addition to their increased risk of progression to end-stage renal disease. Recognizing that the FDA and other regulatory agencies have great interest in both the CV and renal safety and efficacy of compounds under development, pharmaceutical companies should consider inclusion of an appropriate approach to adjudication of potential CV events early in the course of planning for development of drugs to treat DKD.
Adapting current regulatory perspectives
From the regulatory perspective, there is a lot of emphasis focused on looking at both CV and renal risks during the development of type 2 diabetes treatments.1 However, no specific guidance exists for clinically-evident endpoints in DKD. Continue reading →
Of the 422 million people in the world with type 1 and 2 diabetes, 20-30% will develop diabetic nephropathy, also called diabetic kidney disease (DKD) – the leading cause of renal failure in the western world1.
From the perspective of drug developers, testing new therapies to prevent, treat or reverse this serious complication relies on biomarkers for timely and accurate patient identification and efficacy or safety monitoring.
Jennifer Ennis, MD, medical director at LabCorp and D. Walt Chandler, PhD, executive director at LabCorp, recently shared their thoughts on today’s biomarkers to detect and monitor DKD.
Practicing physicians frequently obtain laboratory assessments of kidney function in their routine management of patients with diabetes. Two tests that are commonly performed are the estimated glomerular filtration rate (eGFR) and the urinary albumin to creatinine ratio (ACR). Results of these tests are often used to determine patient eligibility for clinical trials of drugs to treat patients with diabetic kidney disease (DKD).
One challenge that drug developers and clinical trialists face is in choosing eGFR and ACR criteria that support the aims of the clinical study—without hindering recruitment.
To address this issue, researchers at Covance and LabCorp queried a LabCorp database of 329,841 diabetic patients to analyze real-world data. They wanted to understand the distribution of eGFR and ACR values among diabetic patients in the United States and assess how these laboratory parameters predicted renal disease progression.
Pharmacokinetic (PK) data guide the safe and effective management of a drug treatment; however, with diabetic patients, PK studies can be especially challenging. Varying degrees of kidney disease in patients can affect the PK characteristics of the drug and the reliability of the study results.
From screening patients to determining doses, testing a drug for diabetic patients involves several important considerations.
The importance of early work
Even before a drug reaches the clinical stages, early work can help set the stage. Preclinical research is very important in identifying agents with activity in the diabetic spectrum, while studies in early toxicology provide valuable direction as to whether the risks are acceptable in the diabetic population.
Given that most diabetic drugs affect the kidneys, performing an early renal study on a model can determine if the drug has a future in the diabetic space and may help guide earlier go/no-go decisions ‒ before allocating additional resources to the efforts. Continue reading →
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Going Virtual: Evolving Real World Evidence Study Design for Speed, Flexibility and Lower Cost
Using a traditional clinical-site recruitment approach is no longer the only option in observational research. With the increased adoption of electronic informed consent methods by the FDA, it is now feasible to conduct real world evidence (RWE) studies using a virtual model that eliminates entirely the need for clinical sites.
Join us to learn how to lower cost and improve the efficacy of current, site-based RWE studies as well as:
The implications of electronic informed consent by the FDA
What is required to conduct a prospective virtual RWE study
How to use electronic data for a retrospective virtual RWE study