The Synergistic Treatment of Heart and Kidney Disease.

New Glucose-Lowering Agents for Diabetic Kidney Disease.

New Medications for the Treatment of Diabetes

Diabetes is a global emergency involving >463 million people as of 2019 and a projection for growth to nearly 700 million by 2045. The vast majority of people (>95%) with diabetes have type 2 diabetes. Despite what is known about effective lifestyle and pharmacologic interventions, the number of

Chronic kidney disease (CKD) affects around 10% of the global population and is most often caused by diabetes. Diabetes with CKD (diabetic kidney disease, DKD) is a progressive condition that may cause kidney failure and which contributes significantly to the excess morbidity and mortality in these patients. DKD is treated with direct disease-targeting therapies like blockers of the renin–angiotensin system, sodium–glucose cotransporter-2 (SGLT-2) inhibitors and non-steroidal mineralocorticoid receptor antagonists as well as indirect therapies impacting hyperglycaemia, dyslipidaemia, obesity and hypertension, which all together reduce disease progression. While no glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are currently indicated to improve kidney outcomes, accumulating evidence from cardiovascular outcomes trials (CVOTs) corroborates a kidney-protective effect in people with T2D and CKD, and GLP-1 RAs are now mentioned in international treatment guidelines for type 2 diabetes (T2D) with CKD. GLP-1 RAs are indicated to improve glycaemia in people with T2D; certain GLP-1 RAs are also approved for weight management and to reduce cardiovascular risk in T2D. Ongoing pivotal trials are assessing additional indications, including T2D with CKD. In this article, we review and discuss kidney outcomes from a multitude of completed clinical trials as well as real-world evidence and ongoing clinical trials.

ObjectiveTo compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide...

Contemporary management of advanced chronic kidney disease: An evidence-based review.

Time to Follow the Evidence: Glycemic Control and Cardiovascular Benefits of New Diabetes Medications

Chapter 14 - Glucagon-like peptide-1 receptor agonists: role in the prevention and treatment of diabetes-related cardiovascular complications

To assess treatment eligibility for, and received treatment with, sodium-glucose co-transporter 2 inhibitors (SGLT2) and glucagon-like peptide-1 (GLP-1) receptor agonists according to the 2019 the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus report and the 2019 European Society of Cardiology (ESC) guidelines in a nationwide sample of patients with type 2 diabetes. Both sets of guidelines included the treatment indications of heart failure, chronic kidney disease, and atherosclerotic cardiovascular disease while only the 2019 ESC guidelines also recommended treatment based on high or very high cardiovascular risk. The analyses included 435 000 patients with type 2 diabetes identified from the Swedish National Diabetes Register (2020-21). According to the 2019 ESC guidelines, 79.5% were recommended any of the two drugs (SGLT2 inhibitors: 37.2%; SGLT2 inhibitors or GLP-1 receptor agonists: 40.9%; GLP-1 receptor agonists: 1.4%). According to the 2019 ADA/EASD consensus report, 48.8% were recommended any of the two drugs (SGLT2 inhibitors: 37.2%; GLP-1 receptor agonists: 11.6%). Of those who had been recommended any of the two drugs, 33.7% had received the recommended treatment according to the 2019 ESC guidelines and 25.4% according to the 2019 ADA/EASD consensus report. In this nationwide study, the proportion of patients with type 2 diabetes who were recommended treatment with an SGLT2 inhibitor or a GLP-1 receptor agonist was approximately 80% according to the 2019 ESC guidelines and around half according to the 2019 ADA/EASD consensus report. Uptake of these recommendations in routine clinical practice was limited.

Evolution of Mineralocorticoid Receptor Antagonists in the Treatment of Chronic Kidney Disease Associated with Type 2 Diabetes Mellitus.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Optimising Access to Care for Patients with Heart and Kidney Diseases: A World Heart Federation and International Society of Nephrology White Paper

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of incretin-based therapies for the management of hyperglycemia and, in some cases, cardiovascular risk in people with type 2 diabetes. These agents act on multiple physiological pathways involved in type 2 diabetes with the effect of increasing insulin secretion and decreasing glucagon to control glucose levels (1,2). They also transiently slow gastric emptying, reduce appetite, and facilitate weight loss and other metabolic improvements (3). Consensus recommendations from the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) and American Association of Clinical Endocrinologists/American College of Endocrinology advocate that GLP-1 receptor agonists, among other therapies, should be considered as a second-line treatment option in people with type 2 diabetes when glucose levels are not well controlled on metformin (4–6). Additionally, in patients with type 2 diabetes and atherosclerotic cardiovascular disease or chronic kidney disease, a GLP-1 receptor agonist or sodium–glucose cotransporter 2 (SGLT2) inhibitor with proven cardiovascular benefit is recommended as a first-line therapy for the reduction of cardiovascular risk (4–6). GLP-1 receptor agonists may also be used as a first-line treatment in those who cannot use metformin or when reduced renal function precludes metformin use (human-based GLP-1 receptor agonists only) (4–6). In particular, the recommendations favor GLP-1 receptor agonists and SGLT2 inhibitors because they have a low risk of hypoglycemia and promote weight loss (5). Several GLP-1 receptor agonists are available in the United States and worldwide, some of which are analogs of human GLP-1 (dulaglutide, liraglutide, and semaglutide), whereas others are exendin-based (exenatide and lixisenatide) (7–13). The GLP-1 receptor agonist albiglutide was also approved, but has been withdrawn for commercial reasons. Until recently, all GLP-1 receptor agonists were administered by subcutaneous injection, although a once-daily oral formulation …

Aim The 2024 European Society of Cardiology (ESC) guidelines recommend initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists in patients with chronic coronary syndrome (CCS) and type 2 diabetes mellitus (T2DM), irrespective of glycated haemoglobin levels or pre-existing glucose-lowering therapies. This audit evaluated the proportion of T2DM patients undergoing elective coronary artery bypass grafting (CABG) discharged on these medications. Method A retrospective, single-institution audit was conducted between 01/09/2024 and 31/10/2024. We reviewed pre-operative and discharge medications for patients with T2DM who underwent elective CABG, either as a standalone procedure or in combination with other procedures. Data on patient demographics, allergies, and glucose-lowering therapies before admission and on discharge were collected. Results Of the 78 patients who underwent an elective CABG during the study period, 35% (n=27) had a diagnosis of T2DM. Among these, 26% (n=7) were already on an SGLT2 inhibitor or GLP-1 receptor agonist before admission. 37% (n=10) were discharged on either SGLT2 inhibitors only (n=8) or a combination of both medications (n=2). Dapagliflozin, the most prescribed SGLT2 inhibitor (n=6), was initiated in 3 patients during admission, owing to heart failure. Conclusions The first audit cycle revealed that the ESC guidelines were not being adhered to, with only 37% of eligible patients discharged on SGLT2 inhibitors or GLP-1 receptor agonists. Non-adherence to guidelines may stem from limited education following recent release. Educational interventions are underway to improve clinician familiarity with the guideline, which could enhance cardiovascular outcomes for patients with T2DM and CCS. A re-audit is planned for February 2025.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1a), and non-steroidal mineralocorticoid receptor antagonists (ns-MRA) are promising treatments for chronic kidney disease. This umbrella review of network meta-analyses evaluated their effects on cardiovascular outcomes, kidney disease progression, and adverse events, using the TOPSIS method to identify the optimal intervention based on P-scores. A total of 19 network meta-analyses and 44 randomized controlled trials involving 86,150 chronic kidney disease patients were included. Compared to placebo, SGLT2i were associated with reduced risks of cardiovascular events [Hazard ratio (HR): 0.776, 95% confidence intervals (CI): 0.727-0.998], kidney disease progression (HR: 0.679, 95% CI: 0.629-0.733), acute kidney injury (HR: 0.873, 95% CI: 0.773-0.907), and serious adverse events (HR: 0.881, 95% CI: 0.847-0.916). GLP1a and ns-MRA were also associated with significant reductions in cardiovascular and kidney-specific composite outcomes. Indirect evidence showed that SGLT2i demonstrated a lower risk of kidney disease progression compared to GLP1a (HR: 0.826, 95% CI: 0.716-0.952) and ns-MRA (HR: 0.818, 95% CI: 0.673-0.995), representing the best intervention across all endpoints. In conclusion, while SGLT2i, GLP1a, and ns-MRA all reduce cardiovascular and kidney disease risks in chronic kidney disease, SGLT2i appears to provide the most favorable balance of efficacy and safety.