CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

Prioritizing obesity treatment: expanding the role of cardiologists to improve cardiovascular health and outcomes.

Obesity is a major risk factor for cardiovascular disease, yet management remains poor. Cardiologists and healthcare professionals treating people with high cardiovascular risk are in a position to address overweight and obesity to improve cardiovascular health. There are several treatment options for obesity, which are associated with numerous health benefits. Modest weight reductions of 5-10% improve cardiovascular risk factors, with greater weight loss bringing about greater benefits. Anti-obesity medications can support weight reduction when lifestyle modifications alone are insufficient. The weight loss induced by these treatments can improve cardiovascular risk, and some therapies - such as glucagon-like-peptide-1 analogues - may promote these benefits independently of weight loss. Bariatric surgery can induce greater weight losses than other treatment modalities and is associated with numerous health benefits, but newer medications such as semaglutide and those in development, such as tirzepatide, produce robust weight loss efficacy that is approaching that of bariatric surgery. Healthcare professionals must approach this disease with compassion and collaborate with patients to develop sustainable plans that improve health and maintain weight loss over the long term.

Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial.

AIM: To compare the efficacy and safety of once-weekly (OW) semaglutide versus thrice-daily (TID) insulin aspart (IAsp) in participants with inadequately controlled type 2 diabetes (T2D) treated with insulin glargine (IGlar) and metformin. MATERIALS AND METHODS: SUSTAIN 11 (NCT03689374) was a randomized (1:1), parallel, open-label, multinational, phase 3b trial. After a 12-week run-in to optimize once-daily IGlar U100, 1748 adults with T2D (HbA1c >7.5% to ≤10.0%) were randomized to OW semaglutide or TID IAsp as add-on to optimized IGlar and metformin for 52 weeks. The primary outcome was change in HbA1c from randomization to week 52. Confirmatory secondary endpoints included the occurrence of severe hypoglycaemic episodes and change in body weight (BW). Safety was assessed. RESULTS: HbA1c (randomization: 8.6% [70.0 mmol/mol]) decreased by 1.5% points (16.6 mmol/mol) and 1.2% points (13.4 mmol/mol) with semaglutide (n = 874) and IAsp (n = 874), respectively (estimated treatment difference [ETD] -0.29% points [95% confidence interval {CI} -0.38; -0.20]; P < .0001 for non-inferiority). Few severe hypoglycaemic episodes were recorded in either group, with no statistically significant difference between the groups. Change in BW from randomization (87.9 kg) to week 52 was in favour of semaglutide (-4.1 kg) versus IAsp (+2.8 kg) (ETD -6.99 kg [95% CI -7.41; -6.57]). A higher proportion of participants experienced adverse events with semaglutide (58.5%) versus IAsp (52.1%); most were mild to moderate. CONCLUSIONS: In this basal insulin-treated population, OW semaglutide improved glycaemic control to a greater extent than TID IAsp and provided numerically greater weight loss.

Cardiovascular outcome trials in obesity: A review.

Obesity is a global epidemic associated with over 200 health complications and a significant risk of developing cardiovascular disease (CVD), partly by increasing classical risk factors such as lipid and glucose levels and blood pressure. Weight loss through lifestyle interventions, pharmacotherapy and/or bariatric surgery improves CV risk factors. Cardiovascular outcome trials (CVOTs) of anti-obesity medications aim to evaluate the CV safety and benefits of pharmacotherapy. Many CVOTs in obesity have either failed to demonstrate a CV benefit or have been terminated prematurely because of safety issues, prompting regulatory agencies to define new requirements (based on those for CVOTs in type 2 diabetes [T2D]). CVOTs of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in T2D have demonstrated that some GLP-1RAs reduce CV risk and may help inform future CVOTs in obesity, given the approval of liraglutide 3.0 mg for obesity. In this review, the evidence for the link between obesity and CVD is considered in the context of studies showing that weight loss improves markers of CV risk and risk of adverse CV events. The review also examines the CVOTs in obesity that have been conducted to date and those under way, such as the SELECT trial with subcutaneous semaglutide of 2.4 mg.

Traumatic hemipelvectomy in children: report on 2 survivors with urological involvement.

Traumatic hemipelvectomy through the sacroiliac joint is a devastating injury, mainly because of motor vehicle accidents. Recent improvements in prehospital trauma care have increased the chances of survival for victims. Besides amputation of the lower limb, associated complications usually involve digestive and urological systems. We report on 2 pediatric patients from 2 different European countries. PATIENT 1: A 9-year-old boy suffered uprooting of his left lower limb, laceration of the rectum and anal sphincter, as well as an injury to distal urethra with partial loss of cavernous bodies. Initial management included a colostomy and an essay of contention by means of a polypropylene prosthesis that had to be removed in the following months. After several attempts at urethral reconstruction, he underwent a Mitrofanoff derivation. PATIENT 2: An 18-month-old girl lost her left lower limb and suffered severe lacerations of bladder and rectum. Among other measures, management included a colostomy, a skin graft, and 2 attempts at reconstruction of her bladder neck, including a modified Casale procedure (cecum and ileocecal appendix were in a high position that made a Mitrofanoff derivation impossible) and a Malone procedure. To the authors' knowledge, she would be the youngest reported survivor of this kind of injury.

Engaging and empowering patients to manage their type 2 diabetes, Part II: Initiatives for success.

Type 2 diabetes (T2D) has reached pandemic proportions. The impact of it and its long-term sequelae represent a significant burden for many healthcare systems around the world, and a significant number of patients struggle to achieve the internationally recommended targets for the modifiable risk factors that optimize healthy outcomes. In the first part of this two-part review, the scene was set showing that there seems to be a knowledge, attitude, and practice (KAP) gap hindering successful management of T2D. Although theoretical knowledge about how T2D should be managed exists, the attitude of patients and healthcare professionals seems to influence the practicalities of implementing life-enhancing changes for patients living with diabetes. Following the chronic care model, macro-level initiatives such as Finland's national diabetes program, "The Development Programme for the Prevention and Care of Diabetes" (DEHKO), encourage a coordinated, supportive policy and financial environment for healthcare system change, and are advocated by the International Diabetes Federation. Over a 10-year period, the DEHKO program aims to demonstrate that a top-down population approach to prevention, focusing on reducing obesity, increasing physical activity, and encouraging healthier eating habits, may improve the overall health of the nation. However, the patient is the focus of day-to-day management of T2D, and innovative strategies that use a community (meso-level) approach to encourage self-management, or that embrace new technologies to access diabetes self-management education or support networks, are likely to be the way forward. Such measures may close the apparent KAP gap and bring about real and measurable benefits in quality of life and life expectancy. The second part of this review describes some of the many and varied initiatives designed to engage and empower patients to self-manage their T2D, with the aim of increasing the proportion of patients reaching health-related targets. This will ultimately impact on national health systems and the quality of life of the nation.