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 ).

CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes.

The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10-12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year's focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23-24, 2023 ( http://www.cvot.org ).

Report from the CVOT Summit 2021: new cardiovascular, renal, and glycemic outcomes.

The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18-19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year's focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1-5, and STEP 1-5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed.Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10-11, 2022 ( http://www.cvot.org ).

Effects of analogue insulin in multiple daily injection therapy of type 2 diabetes on postprandial glucose control and cardiac function compared to human insulin: a randomized controlled long-term study.

BACKGROUND: The prevention of cardiovascular disease, including diastolic cardiac dysfunction with its high prevalence and ominous prognosis, is a therapeutic challenge for patients with type 2 diabetes. Both short and long-acting insulin analogues (AI) have been shown to reduce glucose variability and provide potential benefit for cardiovascular disease although the effects on cardiac function have not yet been evaluated. This long-term, prospective, randomized controlled trial in patients with type 2 diabetes (T2D) tested the hypothesis that a multiple daily injection regimen (MDI) with AI improves postmeal glucose excursions in comparison to human insulin (HI) and that the effects of AI improve diastolic cardiac function. METHODS: For 36 months, MDI treatment in 109 T2D patients was adapted every 3 months (targets: fasting glucose ≤ 110 mg/dl, postmeal glucose ≤ 150 mg/dl) in both groups: AI (insulin detemir and insulin aspart, n = 61) and HI (NPH-insulin and regular HI, n = 48). Diastolic cardiac function (myocardial velocity E' using tissue Doppler imaging and the mitral inflow ratio E/A) and vascular function were assessed before and 2 h after a standardized breakfast (48 g carbohydrates). At baseline, both groups were comparable with regards to demographic, cardiac and metabolic data. Analysis of data included traditional statistics as well as the use of a multiple imputation technique shown in brackets [ ]. RESULTS: At 36 months, the primary endpoint, postmeal glucose, decreased by 20 ± 62 mg/dl, p = 0.038 [p = 0.021] with AI and increased insignificantly with HI (inter-group p = 0.032 [p = 0.047]) to postmeal glucose levels of 161 ± 39 with AI vs. 195 ± 54 mg/dl with HI (inter-group p = 0.002 [p = 0.010]) whereas the levels of fasting glucose and HbA1c were comparable. With AI, postmeal E' improved by 0.6 ± 1.4 cm/s, p = 0.009 [p = 0.002] and fasting E' by 0.4 ± 1.4 cm/s, p = 0.069 [p = 0.013], however, E' remained unchanged with HI. These changes were consistent with those of the traditional parameter E/A. CONCLUSIONS: MDI with AI results in better postmeal glucose control compared to HI. The treatment with AI is associated with improved diastolic cardiac function. ClinicalTrials.gov (NTC00747409).

What is the role of general internists in the tertiary or academic setting?

The changing demography of European populations mandates a vital role for internists in caring for patients in each level of healthcare. Internists in the tertiary or academic setting are highly ranked in terms of their responsibilities: they are clinicians, educators, researchers, role models, mentors and administrators. Contrary to the highly focused approach of sub-specialties, general internists working in academic settings can ensure that coordinated care is delivered in the most cost-conscious and efficient way. Moreover, internal medicine is one of the most appropriate specialties in which to teach clinical reasoning skills, decision-making and analytical thinking, as well as evidence based, patient oriented medicine. Internists deal with challenging patients of the new millennium with a high burden of chronic diseases and polypharmacy; practice personalised medicine with a wide scientific background and so they are the perfect fit to establish and implement new tools for scientific research. In conclusion, internal medicine is developing a new identity as a specialty in its own right. The European Federation of Internal Medicine supports the concept of academic internists and calls upon the member countries to construct academic (general) internal medicine departments in their respective countries. As 'internal medicine is the cornerstone of every national healthcare system', academic (general) internal medicine should strive to be the cornerstone of every integrated, patient-centred, modern medical care and training system.

The role of co-morbidity in the selection of antidiabetic pharmacotherapy in type-2 diabetes.

Metformin is, if not contraindicated and if tolerated, usually preferred over other antidiabetic drugs for the first line treatment of type-2 diabetes. The particular decision on which antidiabetic agent to use is based on variables such as efficacy, cost, potential side effects, effects on weight, comorbidities, hypoglycemia, risk, and patient preferences. However, there is no guidance how to consider these in the selection of antidiabetic drug treatment. In this work, we aimed to summarize available evidence and tried to give pragmatic treatment recommendations from a clinical practice perspective.There are clear contraindications for some drugs in those with impaired renal and liver function and precautions in those with heart failure for the use of metformin (NYHA III-IV) and glitazones. On the other hand, GLP-1 analogs, DPP-4 inhibitors and acarbose are generally less critical and can be used in the majority of patients. We identified the following gaps with respect to the selection of antidiabetic drug treatment in patients with co-morbid disease conditions: 1) Guidelines fail to give advice on the use of specific antidiabetic drugs in patients with co-morbidity. 2) The literature is deficient in studies documenting antidiabetic drug use in patients with severely impaired renal function, diabetic retinopathy, cerebrovascular disease and systolic heart failure. 3) Further there are no specific data on patients with multiple of these co-morbid disease conditions. We postulate that differential use of antidiabetic drugs in patients with co-morbid disease constellations will help to reduce treatment related complications and might improve prognosis.

Should antidiabetic treatment of type 2 diabetes in patients with heart failure differ from that in patients without?

AIMS: Patients with type 2 diabetes are at high risk for developing heart failure. Evidence-based treatment recommendations with respect to the specific benefits or possible hazards of antidiabetic treatment are scarce. METHODS AND RESULTS: In a systematic search we only identified randomized, controlled trials for thiazolidinediones. Further evidence is largely based on subgroup analyses of larger intervention studies in mostly systolic heart failure, on observational studies, or on registries. Acknowledging this lack of data, hyperglycaemia should be treated to appropriate guideline-recommended targets and hypoglycaemia avoided until this evidence becomes available. Thiazolidinediones should not be used because of an increased event rate in diabetic patients with established heart failure and a large increase in incident heart failure. All other glucose-lowering strategies might be used in patients with diabetes and heart failure, but specific precautions must be considered. CONCLUSIONS: The documented lack of data calls for specific trials, as diabetes and heart failure as well as their co-morbidities are highly prevalent and are becoming even more important with an increasing prevalence of obesity and an ageing population.

Comparison of usability and patient preference for insulin pen needles produced with different production techniques: "thin-wall" needles compared to "regular-wall" needles: an open-label study.

BACKGROUND: People with diabetes mellitus on insulin therapy increasingly prefer insulin pens over syringes and vials. Different types of pen needles are available for insulin pens, e.g., "thin-wall" needles, which have the same outer diameter but a relatively lager inner diameter compared to needles produced with a "regular-wall." METHODS: We conducted a multicenter open-label, single-arm study in patients (n = 97) with diabetes mellitus using insulin pens. The aim of our study was to evaluate pen user habits as well as to assess patient's appraisals and ratings considering two different types of 31-gauge pen-needles, so-called "thin-wall" needles or "regular-wall" needles." Patients twice underwent a 2-week intervention period, starting with a "regular-wall period" followed by a "thin-wall-period." After each period patients filled in questionnaires. RESULTS: In total, 97 diabetes patients (48% female; mean age, 56 years; range, 20-70 years) completed the study. Patients reported significantly less pain, less bleeding, less skin irritation, less injection strain, less residual insulin leakage from the needle tip after injection, and less needle occlusion when using "thin-wall needles" (P < 0.001). A higher proportion of patients expressed an overall preference for the "thin-wall" needles (78%) compared to the "regular-wall" needles (8%) (P < 0.001). CONCLUSIONS: Pen and pen needle handling, preparation, and execution of injections should be a part of repeated diabetes education and be re-evaluated on a regular basis. The "thin-wall" 31-gauge needle was found to be more user-friendly and consequently preferred by the patients. Additional larger-scale trials using blinded and randomized study designs are needed to validate these findings.