Sodium-glucose cotransporter-2 inhibition for heart failure with preserved ejection fraction and chronic kidney disease with or without type 2 diabetes mellitus: a narrative review.

BACKGROUND: Heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) are common and interrelated conditions, each with a significant burden of disease. HF and kidney disease progress through pathophysiologic pathways that culminate in end-stage disease, for which T2DM is a major risk factor. Intervention within these pathways can disrupt disease processes and improve patient outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been investigated in patient populations with combinations of T2DM, CKD, and/or HF. However, until recently, the effect of these agents in patients with HF with preserved ejection fraction (HFpEF) was not well studied. MAIN BODY: The aim of this review is to summarize key information regarding the interaction between HFpEF, CKD, and T2DM and discuss the role of SGLT2 inhibition in the management of patients with comorbid HFpEF and CKD, with or without T2DM. Literature was retrieved using Boolean searches for English-language articles in PubMed and Google Scholar and included terms related to SGLT2is, HFpEF, T2DM, and CKD. The reference lists from retrieved articles were also considered. CONCLUSION: SGLT2is are efficacious and safe in treating HFpEF in patients with comorbid CKD with and without T2DM. The totality of evidence from clinical trials data suggests there are benefits in using SGLT2is across the spectrum of left ventricular ejection fractions, but there may be a potential for different renal effects in the different ejection fraction groups. Further analysis of these clinical trials has highlighted the need to obtain more accurate phenotypes for patients with HF and CKD to better determine which patients might respond to guideline-directed medical therapies, including SGLT2is. CI confidence interval, EF ejection fraction, eGFR estimated glomerular filtration rate, HF heart failure, HHF hospitalization for HF, HR hazard ratio, LVEF left ventricular ejection fraction, SGLT2i sodium-glucose cotransporter-2 inhibitor, UACR urine albumin-creatinine ratio. a Mean value, unless otherwise stated, b SGLT2i vs. placebo, c Data reanalyzed using more conventional endpoints (≥ 50% sustained decrease in eGFR, and including renal death) (UACR at baseline not stated in trial reports).

Overuse of long-acting ß2-agonist/inhaled corticosteroids in patients with chronic obstructive pulmonary disease: time to rethink prescribing patterns.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality globally. In the major revision of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report, the scientific committee concluded that the use of long-acting ß2-agonist/inhaled corticosteroids (LABA/ICS) is not encouraged in patients with COPD. However, current prescribing patterns reveal significant use of LABA/ICS. In this paper, the evidence behind the current practice and the latest treatment recommendations is reviewed. We compare the efficacy and safety of combination therapy with long-acting muscarinic antagonist (LAMA) and LABA vs LABA/ICS and note that LAMA/LABA combinations have reduced the annual rate of moderate/severe exacerbations, delayed the time to first exacerbation, and increased post-dose FEV1 vs ICS-based regimens. The GOLD 2023 report recommends treatment with LABA and LAMA combination (preferably as a single inhaler) in patients with persistent dyspnea, with initiation of ICS in patients based on the symptoms (dyspnea and exercise intolerance as indicated by modified Medical Research Council [mMRC] score ≥ 2 and COPD Assessment Test [CAT™] > 20), blood eosinophil count (≥ 300 cells/µL), and exacerbation history (history of hospitalizations for exacerbations of COPD and ≥ 2 moderate exacerbations per year despite appropriate long-acting bronchodilator maintenance therapy). We describe practical recommendations for primary care physicians to optimize therapy for their patients and prevent overuse of ICS-based regimens. We advocate adherence to current recommendations and a greater focus on effective treatments to successfully control symptoms, minimize exacerbation risk, preserve lung function, maximize patient outcomes, and reduce the burden of drug-related adverse events.

Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs associated with continued respiratory symptoms and airflow limitation. COPD causes symptoms such as breathlessness, cough, and production of phlegm, and, if not properly managed, these symptoms may get worse and result in flare-ups, also termed exacerbations. COPD management includes controlling symptoms while reducing the risk of exacerbations. COPD treatments include bronchodilators and inhaled corticosteroids (ICS). Bronchodilators help by widening the airways, making it easier to breathe. The two types of bronchodilators are long-acting muscarinic antagonists (LAMAs; these drugs prevent closing of the airways) and long-acting ß₂-agonists (LABAs; these drugs relax the muscles around the airways to help keep the airways open for a longer time). ICS may reduce swelling in the airways in some patients with COPD. However, the use of ICS-based regimens as the first treatment choice has been linked to health risks and is not in keeping with the recent national and international recommendations. In this narrative review, we examine why the use of ICS-based regimens is still growing and explore, based on available evidence, and why this treatment course may not be optimal for most patients with COPD. We discuss how the treatment for COPD has changed over time, and our findings support the use of LAMA and LABA as the first course of therapy in many patients with COPD. We conclude that greater adherence to the treatment guidelines can help to improve treatment outcomes for many patients with COPD.

New Paradigms for CKD Management in Patients With T2D.

LEARNING OBJECTIVES: At the end of the activity, participants will be able to: Identify the risks of kidney disease and their consequences in patients with type 2 diabetes (T2D). Appropriately screen for the presence of chronic kidney disease (CKD) in patients with T2D. Initiate evidence-based therapy to slow the progression of kidney disease in patients with T2D and CKD. Become familiar with the novel nonsteroidal mineralocorticoid receptor antagonist finerenone and its role in the treatment of patients with T2D and CKD.

CRS Diabetes: An Effective Model for Improving Family Medicine Resident Knowledge, Competence, and Performance in Diabetes Care.

The Chief Residents Summit on Intensifying Diabetes Management, now in its 15th year, has resulted in real-world improvements in patient outcomes and has shown itself to be an effective model for teaching diabetes to family medicine residents. This article describes the program and the evidence supporting its effectiveness.

Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how?

Oral semaglutide is the first US Food and Drug Administration-approved oral glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes (T2D). Prior articles within this supplement reviewed the PIONEER trial program, which demonstrated that oral semaglutide reduced glycated hemoglobin and body weight when given to patients with uncontrolled T2D on various background therapies, and had a safety profile consistent with subcutaneous GLP-1RAs. This article provides guidance on integrating oral semaglutide into clinical practice in primary care. Patient populations with T2D who may gain benefit from oral semaglutide include those with inadequate glycemic control taking one or more oral glucose-lowering medication (e.g. after metformin), patients for whom weight loss would be beneficial, patients at risk of hypoglycemia, those who would historically have been considered for treatment with a subcutaneous GLP-1RA, and those receiving basal insulin who require treatment intensification. Like other GLP-1RAs, oral semaglutide is contraindicated in those with personal/family history of medullary thyroid carcinoma, and in those with multiple endocrine neoplasia syndrome type 2, as noted in a boxed warning in the prescribing information. Oral semaglutide has not been studied in those with a history of pancreatitis, is not recommended in patients with suspected/confirmed pancreatitis, and is not indicated in type 1 diabetes. When initiating oral semaglutide, gradual dose escalation is recommended to minimize the risk of gastrointestinal adverse events. As food and excess liquid reduce oral semaglutide absorption, patients should swallow the tablet with up to 4 fl oz/120 mL of water on an empty stomach upon waking, and should wait at least 30 minutes before eating, drinking, or taking other oral medications. Those managing patients should be aware of the potential impact of these dosing conditions on concomitant medications. When counseling patients, it is important to discuss these administration instructions, realistic therapeutic expectations, and strategies for mitigation of gastrointestinal events. Oral semaglutide provides a new option for add-on to initial T2D therapy (or later in the treatment paradigm), with the potential to enable more patients to benefit from the improvements in glycemic control, reductions in body weight, and low risk of hypoglycemia afforded by GLP-1RAs.

GLP-1 receptor agonists in the treatment of type 2 diabetes: role and clinical experience to date.

Glucagon-like peptide-1 (GLP-1) is a hormone of the incretin system responsible for a variety of glucoregulatory effects, including glucose-dependent secretion of insulin and inhibition of glucagon release, the effects of which are impaired in people with type 2 diabetes (T2D). Targeting this deficiency using GLP-1 receptor agonists (GLP-1RAs) is a well-established approach in T2D, with over a decade of clinical experience now accrued. This article reviews the evidence for subcutaneous GLP-1RAs and their role in T2D treatment, and explores the rationale for an oral GLP-1RA from a primary care perspective. Clinical trials and real-world studies with subcutaneous GLP-1RAs indicate that these agents have good glycated hemoglobin (HbA1 c)-lowering efficacy, an inherently low potential for hypoglycemia, and reduce body weight. Cardiovascular outcomes trials have established cardiovascular safety, and three GLP-1RAs have been proven to reduce the risk of major adverse cardiovascular events (MACE) in patients with established cardiovascular disease or at high cardiovascular risk. The most common adverse events associated with GLP-1RAs are gastrointestinal effects, which tend to occur soon after initiation and decline over time. T2D treatment guidelines recommend GLP-1RAs as a therapeutic option in various settings, including in those patients: i) not achieving HbA1 c targets after first-line metformin and lifestyle modifications; ii) at high risk of/with established atherosclerotic cardiovascular disease (regardless of HbA1c; GLP-1RAs of proven benefit); iii) not achieving HbA1 c targets on basal insulin if not already receiving a GLP-1RA. Despite the known benefits of GLP-1RAs, adherence and persistence rates are suboptimal, potentially due in part to injection-related concerns. With some patients having a preference for oral medications, the development of an oral GLP-1RA is a logical approach to improving treatment options for patients with T2D. Co-formulation of semaglutide with an absorption enhancer has enabled the development and recent approval of the first oral GLP-1RA, oral semaglutide, which has the potential to expand use of GLP-1RAs in clinical practice.