Early intervention and intensive management of patients with diabetes, cardiorenal, and metabolic diseases

Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression. To address this gap, we convened a Task Force of experts in cardiology, nephrology, endocrinology, and primary care to develop recommendations for early identification and intervention in obesity, diabetes, and other cardiorenal and metabolic diseases. The recommendations include screening and diagnosis, early interventions with lifestyle, and when and how to implement medical therapies. These recommendations are organized into primary and secondary prevention along the continuum from obesity through the metabolic syndrome, prediabetes, diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular disease (ASCVD) and atrial fibrillation, chronic kidney disease (CKD), and heart failure (HF). The goal of early and intensive intervention is primary prevention of comorbidities or secondary prevention to decrease further worsening of disease and reduce morbidity and mortality. These efforts will reduce clinical inertia and may improve patients\u27 well-being and adherence

Efficacy and safety of insulin glargine/lixisenatide (iGlarLixi) fixed-ratio combination in older adults with type 2 diabetes.

Abstract Aims This study assessed the efficacy and safety of iGlarLixi (a titratable, fixed-ratio combination of insulin glargine [iGlar] plus lixisenatide) in older patients with type 2 diabetes. Methods This post hoc analysis used patient-level data from patients aged ≥65 years from the phase III LixiLan-O and LixiLan-L studies, which compared iGlarLixi with iGlar and lixisenatide (LixiLan-O only). Efficacy endpoints were changes in glycated hemoglobin A1C, fasting plasma glucose, postprandial glucose, weight, and achievement of A1C Results In both trials, older patients treated with iGlarLixi achieved significantly greater reductions in A1C at Week 30 than comparators. Treatment with iGlarLixi mitigated insulin-associated weight gain and lixisenatide-associated gastrointestinal events. Results were largely comparable between patients aged ≥65 versus Conclusions iGlarLixi provides significant improvements in glycemic control in patients aged ≥65 years without increasing hypoglycemia risk. As a once-daily injection, it simplifies treatment regimens and may contribute to improved adherence in this patient population

The CardioMetabolic Health Alliance Working Toward a New Care Model for the Metabolic Syndrome

AbstractThe Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a “call to action” activity focused on defining new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future

Bile Acid Sequestrants for Lipid and Glucose Control

Bile acids are generated in the liver and are traditionally recognized for their regulatory role in multiple metabolic processes including bile acid homeostasis, nutrient absorption, and cholesterol homeostasis. Recently, bile acids emerged as signaling molecules that, as ligands for the bile acid receptors farnesoid X receptor (FXR) and TGR5, activate and integrate multiple complex signaling pathways involved in lipid and glucose metabolism. Bile acid sequestrants are pharmacologic molecules that bind to bile acids in the intestine resulting in the interruption of bile acid homeostasis and, consequently, reduction in low-density lipoprotein cholesterol levels in hypercholesterolemia. Bile acid sequestrants also reduce glucose levels and improve glycemic control in persons with type 2 diabetes mellitus (T2DM). This article examines the mechanisms by which bile acid–mediated activation of FXR and TGR5 signaling pathways regulate lipid and glucose metabolism and the potential implications for bile acid sequestrant–mediated regulation of lipid and glucose levels in T2DM

Overcoming obstacles in risk factor management in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is characterized by progressively worsening hyperglycemia that leads to microvascular and macrovascular complications. Optimal management of T2DM aims to simultaneously control hyperglycemia, hypertension, and dyslipidemia to reduce the overall risk. However, a large proportion of patients in clinical practice do not reach treatment targets. Some of the obstacles to achieving treatment targets include high medication costs, costs associated with health insurance, poor patient adherence to medication, patient fear of potential adverse effects, improper patient education, and failure by health care providers to appropriately initiate or intensify therapy (clinical inertia). Possible causes of clinical inertia include the influence exerted on physicians by reluctant patients and the influence of media-driven attention and the negative spin of clinical trial results on physicians' prescribing behavior and on patients' attitudes towards treatment. This negative publicity can be disproportionate to the overall body of scientific evidence and may, therefore, prove to be unfounded in the long-term. There is clear evidence of the benefits of the effective management of T2DM to achieve goals. Overcoming the obstacles to achieving treatment targets may include use of strategies such as early intensive treatment and combination therapy with drugs with complementary mechanisms of action

Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine

Abstract: Estimates suggest that there are currently 122.8 million adults 65–99 years of age living with diabetes, of whom 90–95% are diagnosed with type 2 diabetes (T2D). Over the past two decades, a greater understanding of the complex and multifactorial pathogenesis of T2D has resulted in the development and introduction of new-generation classes of glucose-lowering therapies, which are now extensively endorsed by prevailing guidelines and are increasingly being used worldwide. These newer agents may further assist in the effective pharmacological management of T2D through the provision of patient-centered care that acknowledges multimorbidity and is respectful of and responsive to individual patient preferences and barriers. Given these considerations, the therapeutic approach in older patients with T2D is complex, particularly in those who have functional dependence, frailty, dementia, or who are at end-of-life. It is currently too early to draw conclusions on the long-term use of newer glucose-lowering agents in this population, as their efficacy and safety in older adults remains largely unknown. In this review, we will discuss considerations for the use of glucose-lowering treatments in older adults, with particular focus on the use of basal insulin and glucagon-like peptide-1 receptor agonists, and the rationale for the use of combination therapy comprising these agents. Finally, we will review clinical data from studies of the fixed-ratio combination of insulin glargine and lixisenatide in older patients with T2D. Funding: Sanofi US, Inc

Correction to: Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine (Advances in Therapy, (2019), 36, 12, (3321-3339), 10.1007/s12325-019-01126-x)

On page 3331 of the original article, the word, ‘‘/LYXUMIA’’ has been removed from the section RATIONALE FOR COMBINATION THERAPY COMPRISING GLP-1 RAs AND BASAL INSULIN and the associated reference, numbered 100, has been corrected to: Xultophy® (insulin degludec/liraglutide) [summary of product characteristics]. Bagsvaerd, Denmark: Novo Nordisk A/S https://www.ema.europa.eu/ en/documents/product-information/xultophyepar- product-information_en.pdf. Accessed November 2019