Langerhans Cell Histiocytosis of the Suprasellar Region: Diagnosis on Thyroid Cytology.

Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D) and weight gain. Transcranial biopsy is necessary, to define diagnosis and guide treatment decisions, but is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was done through thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose avidity on positron emission tomography/-computed tomography (FDG-PET/-CT), and volume increase during follow-up.

[Obstetrics and Gynecology. Management and screening for gestational diabetes : what's new in 2023]. / Gynécologie-obstétrique. Prise en charge et dépistage du diabète gestationnel : ce qui a changé en 2023.

Gestational diabetes (GDM) is becoming increasingly common as a result of the increase in overweight, obesity and maternal age among pregnant women. As a result, in order to provide early hygienic and dietary management, it is recommended that targeted screening be carried out in the first trimester of pregnancy, based on the identification of risk factors in women. In the absence of risk factors, screening for gestational diabetes should be carried out for all pregnant women between 24 and 28 weeks' gestation. During pregnancy, the safest pharmacological treatment remains insulin, and the term of delivery should take account of additional risk factors, insulin requirements, fœtal growth kinetics and the balance of GDM. In the longer term, gestational diabetes should be regarded as a metabolic and cardiovascular warning sign.

Dû à l'augmentation du surpoids, de l'obésité et de l'âge maternel chez les femmes enceintes, le diabète gestationnel (DG) est de plus en plus fréquent. De ce fait, afin d'offrir une prise en charge hygiénodiététique précoce, il est recommandé d'effectuer un dépistage ciblé au premier trimestre de la grossesse pour identifier les facteurs de risque. En leur absence, le dépistage du DG doit être réalisé chez toutes les femmes enceintes entre 24 et 28 SA. Au cours de la grossesse, le traitement pharmacologique le plus sécuritaire reste l'insuline et le terme d'accouchement doit tenir compte des facteurs de risque surajoutés, des besoins en insuline, de la cinétique de croissance fœtale et de l'équilibre du DG. À plus long terme, le DG doit être considéré comme une alerte métabolique et cardiovasculaire.

S100A9 exerts insulin-independent antidiabetic and anti-inflammatory effects.

Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency leading to hyperglycemia and several metabolic defects. Insulin therapy remains the cornerstone of T1DM management, yet it increases the risk of life-threatening hypoglycemia and the development of major comorbidities. Here, we report an insulin signaling-independent pathway able to improve glycemic control in T1DM rodents. Co-treatment with recombinant S100 calcium-binding protein A9 (S100A9) enabled increased adherence to glycemic targets with half as much insulin and without causing hypoglycemia. Mechanistically, we demonstrate that the hyperglycemia-suppressing action of S100A9 is due to a Toll-like receptor 4-dependent increase in glucose uptake in specific skeletal muscles (i.e., soleus and diaphragm). In addition, we found that T1DM mice have abnormal systemic inflammation, which is resolved by S100A9 therapy alone (or in combination with low insulin), hence uncovering a potent anti-inflammatory action of S100A9 in T1DM. In summary, our findings reveal the S100A9-TLR4 skeletal muscle axis as a promising therapeutic target for improving T1DM treatment.

[Diabetology: what's new in 2023]. / Diabétologie: ce qui a changé en 2023.

Diabetology is a continuously evolving discipline, many molecules are developed and treatment recommendations change often according to the latest published studies. It is therefore often difficult for the primary care physician to be up to date. After lifestyle measures that must always be preferred before any drug, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects. The purpose of this article is to guide the primary care physician to choose the most suitable pharmacological treatment for each patient, in the light of the 2023 novelties in the field of diabetes.

La diabétologie est une discipline en évolution continue, de nombreuses molécules sont développées et les recommandations de traitement changent fréquemment en fonction des dernières études publiées. Il est donc souvent difficile pour le médecin de premier recours d'être à jour. Après les mesures du style de vie qu'il faut toujours privilégier avant toute approche médicamenteuse, la metformine reste la base pharmacologique du traitement. Les recommandations actuelles préconisent d'instaurer un inhibiteur du SGLT2 ou un agoniste du récepteur du GLP-1 après la metformine car ces molécules ont montré des effets bénéfiques cardiovasculaires et rénaux. Le but de cet article est de fournir une aide au médecin de premier recours dans le choix du traitement pharmacologique le plus adapté à chaque patient, à la lumière des nouveautés 2023 dans le domaine du diabète.

Circadian organization of lipid landscape is perturbed in type 2 diabetic patients.

Lipid homeostasis in humans follows a diurnal pattern in muscle and pancreatic islets, altered upon metabolic dysregulation. We employ tandem and liquid-chromatography mass spectrometry to investigate daily regulation of lipid metabolism in subcutaneous white adipose tissue (SAT) and serum of type 2 diabetic (T2D) and non-diabetic (ND) human volunteers (n = 12). Around 8% of ≈440 lipid metabolites exhibit diurnal rhythmicity in serum and SAT from ND and T2D subjects. The spectrum of rhythmic lipids differs between ND and T2D individuals, with the most substantial changes observed early morning, as confirmed by lipidomics in an independent cohort of ND and T2D subjects (n = 32) conducted at a single morning time point. Strikingly, metabolites identified as daily rhythmic in both serum and SAT from T2D subjects exhibit phase differences. Our study reveals massive temporal and tissue-specific alterations of human lipid homeostasis in T2D, providing essential clues for the development of lipid biomarkers in a temporal manner.

Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

GLP-1 receptor agonists effect on cognitive function in patients with and without type 2 diabetes.

Glucagon-like peptide 1 (GLP-1) is a hormone of the incretin family, secreted in response to nutrient ingestion, and plays a role in metabolic homeostasis. GLP-1 receptor agonist has a peripheral and a central action, including stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. Through their mechanism, their use in the treatment of type 2 diabetes has been extended to the management of obesity, and numerous trials are being conducted to assess their cardiovascular effect. Type 2 diabetes appears to share common pathophysiological mechanisms with the development of cognitive disorders, such as Alzheimer's and Parkinson's disease, related to insulin resistance. In this review, we aim to examine the pathological features between type 2 diabetes and dementia, GLP-1 central effects, and analyze the relevant literature about the effect of GLP-1 analogs on cognitive function of patients with type 2 diabetes but also without. Results tends to show an improvement in some brain markers (e.g. hippocampal connections, cerebral glucose metabolism, hippocampal activation on functional magnetic resonance imaging), but without being able to demonstrate a strong correlation to cognitive scores. Some epidemiological studies suggest that GLP-1 receptor agonists may offer a protective effect, by delaying progression to dementia when diabetic patients are treated with GLP-1 receptor agonists. Ongoing trials are in progress and may provide disease-modifying care for Alzheimer's disease and Parkinson's disease patients in the future.

Role of Oxidative Stress and Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) has become a widely studied subject due to its increasing prevalence and links to diseases such as type 2 diabetes and obesity. It has severe complications, including nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and portal hypertension that can lead to liver transplantation in some cases. To better prevent and treat this pathology, it is important to understand its underlying physiology. Here, we identify two main factors that play a crucial role in the pathophysiology of NAFLD: oxidative stress and the key role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). We discuss the pathophysiology linking these factors to NAFLD pathophysiology.

[The diabetic foot : a complex and multidisciplinary management]. / Pied diabétique : une prise en charge complexe et multidisciplinaire.

Diabetic foot syndrome is a common complication in people with diabetes and peripheral sensory impairment. This complex situation requires early clinical detection by various health care professionals, but also by patients and their relatives. The clinical course, the severity of the prognosis and the management will be determined by the speed of the diagnosis. In the case of confirmed disease, multidisciplinary management is necessary. The most important intervention, both for prevention and treatment, is the discharge of the affected foot.

Le syndrome du pied diabétique est une complication fréquente chez les personnes ayant un diabète et une atteinte de la sensibilité périphérique. Cette situation complexe nécessite une détection clinique précoce, par les divers professionnels de la santé mais aussi par les patients et leurs proches. L'évolution clinique, la gravité du pronostic et la prise en charge seront déterminées par la rapidité du diagnostic. En cas d'atteinte confirmée, une prise en charge multidisciplinaire est nécessaire. L'intervention la plus importante, tant pour la prévention que le traitement, est la décharge du pied atteint.

[Non-Alcoholic Fatty Liver Disease and Diabetes: the bad marriage]. / Stéatopathie non alcoolique (NAFLD) et diabète : le mauvais mariage.

NAFLD, whose prevalence keeps growing, is strongly linked with type 2 diabetes (T2D) through insulin resistance and oxidative stress. A multifactorial association with T1D has recently been found. NAFLD screening aims to identify non-alcoholic steatohepatitis (NASH) and fibrosis and to better refer to liver specialists. It is recommended for patients at higher risk, such as those with T2D. NAFLD treatment cornerstone is weight loss, obtained through lifestyle interventions, obesity pharmacotherapy, and bariatric surgery. When treating patients suffering from NAFLD and T2D, we should prioritize GLP-1 analogues and PPAR agonists, capable of regressing NASH, and SGLT2i, efficient on liver steatosis.

La stéatopathie non alcoolique (NAFLD), dont la prévalence est à la hausse, est une pathologie fortement liée au diabète de type 2 (DT2) par la résistance à l'insuline et le stress oxydatif. Une association multifactorielle avec le diabète de type 1 (DT1) a été récemment mise en évidence. Le dépistage de la NAFLD vise l'identification des formes plus sévères (NASH avec fibrose) et une orientation correcte vers les hépatologues. Il s'adresse à des sous-groupes à risque, dont les patients avec un DT2. La pierre angulaire du traitement de la NAFLD est la perte pondérale, les mesures hygiéno-diététiques, la pharmacologie de l'obésité ou la chirurgie bariatrique. Pour les patients avec NAFLD et DT2, il faut considérer en priorité les analogues du GLP-1 et les agonistes PPAR, capables de faire régresser la NASH, et les iSGLT2, efficaces sur la simple stéatose.

The impact of transsphenoidal surgery on pituitary function in patients with non-functioning macroadenomas.

PURPOSE: Transsphenoidal surgery for non-functioning pituitary adenomas (NFPAs) can alter pituitary function. We assessed the rates of improvement and deterioration of pituitary function by axis and searched for predictive factors of these outcomes. METHODS: We reviewed consecutive medical files from patients having had transsphenoidal surgery for NFPA between 2004 and 2018. Pituitary functions and MRI imaging were analyzed prior and after surgery. The occurrence of recovery and new deficit were documented per axis. Prognostic factors of hormonal recovery and new deficits were searched. RESULTS: Among 137 patients analyzed, median tumor size of the NFPA was 24.8 mm and 58.4% of patients presented visual impairment. Before surgery, 91 patients (67%) had at least one abnormal pituitary axis (hypogonadism: 62.4%; hypothyroidism: 41%, adrenal insufficiency: 30.8%, growth hormone deficiency: 29.9%; increased prolactin: 50.8%). Following surgery, the recovery rate of pituitary deficiency of one axis or more was 46% and the rate of new pituitary deficiency was 10%. Rates of LH-FSH, TSH, ACTH and GH deficiency recovery were 35.7%, 30.4%, 15.4%, and 45.5% respectively. Rates of new LH-FSH, TSH, ACTH and GH deficiencies were 8.3%, 1.6%, 9.2% and 5.1% respectively. Altogether, 24.6% of patients had a global pituitary function improvement and only 7% had pituitary function worsening after surgery. Male patients and patients with hyperprolactinemia upon diagnosis were more likely to experience pituitary function recovery. No prognostic factors for the risk of new deficiencies were identified. CONCLUSION: In a real-life cohort of patients with NFPAs, recovery of hypopituitarism after surgery is more frequent than the occurrence of new deficiencies. Hence, hypopituitarism could be considered a relative indication for surgery in patients with NFPAs.

[News in diabetology: what's new in 2022]. / Diabétologie : ce qui a changé en 2022.

Diabetology is a constantly evolving discipline, many molecules appear on the market and treatment recommendations change quite frequently according to the latest published studies. It is therefore often difficult for the primary care physician to be up to date. After lifestyle measures that must of course be preferred before any drug approach, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects. The purpose of this article is to help the primary care physician to choose the most suitable pharmacological treatment for each patient, in the light of the 2022 novelties in the field of diabetes.

La diabétologie est une discipline en constante évolution. De nombreuses molécules apparaissent sur le marché et les recommandations de traitement changent assez fréquemment en fonction des dernières études publiées. Il est donc souvent difficile pour le médecin de premier recours d'être à jour. Après les mesures sur le style de vie, qu'il faut bien sûr privilégier avant toute approche médicamenteuse, la metformine reste la base pharmacologique du traitement. Les recommandations actuelles préconisent d'instaurer un inhibiteur du SGLT2 (sodium-glucose transporteur de type 2) ou un agoniste du récepteur du GLP-1 (Glucagon-like Peptide-1) après la metformine car ces molécules ont montré des effets bénéfiques cardiovasculaires et rénaux. Le but de cet article est d'aider le médecin de premier recours à choisir le traitement pharmacologique le plus adapté à chaque patient, à la lumière des nouveautés 2022 dans le domaine du diabète.

Non-alcoholic fatty liver disease in type 1 diabetes: Prevalence and pathophysiology.

Non-alcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in the general population with a global prevalence of 25%. It is often associated with metabolic syndrome and type 2 diabetes, as insulin resistance and hyperinsulinemia are known to be favoring factors. Recent studies have described growing incidence of NAFLD in type 1 diabetes (T1D) as well. Although increasing prevalence of metabolic syndrome in these patients seems to explain part of this increase in NAFLD, other underlying mechanisms may participate in the emergence of NAFLD. Notably, some genetic factors are more associated with fatty liver disease, but their prevalence in T1D has not been evaluated. Moreover, oxidative stress, poor glucose control and long-lasting hyperglycemia, as well as exogenous insulin administration play an important role in intrahepatic fat homeostasis. The main differential diagnosis of NAFLD in T1D is glycogenic hepatopathy, which needs to be considered mostly in T1D patients with poor glycemic control. This article aims to review the prevalence and pathophysiology of NAFLD in T1D and open perspectives for clinicians taking care of T1D patients with potential hepatopathy.

Interleukin-18 in metabolism: From mice physiology to human diseases.

Interleukin-18 (IL-18) is a classical member of the IL-1 superfamily of cytokines. As IL-1ß, IL-18 precursor is processed by inflammasome/caspase-1 into a mature and biologically active form. IL-18 binds to its specific receptor composed of two chains (IL-18Rα and IL-18Rß) to trigger a similar intracellular signaling pathway as IL-1, ultimately leading to activation of NF-κB and inflammatory processes. Independently of this IL-1-like signaling, IL-18 also specifically induces IFN-γ production, driving the Th1 immune response. In circulation, IL-18 binds to the IL-18 binding protein (IL-18BP) with high affinity, letting only a small fraction of free IL-18 able to trigger receptor-mediated signaling. In contrast to other IL-1 family members, IL-18 is produced constitutively by different cell types, suggesting implications in normal physiology. If the roles of IL-18 in inflammatory processes and infectious diseases are well described, recent experimental studies in mice have highlighted the action of IL-18 signaling in the control of energy homeostasis, pancreatic islet immunity and liver integrity during nutritional stress. At the same time, clinical observations implicate IL-18 in various metabolic diseases including obesity, type 1 and 2 diabetes and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). In the present review, we summarize and discuss both the physiological actions of IL-18 in metabolism and its potential roles in pathophysiological mechanisms leading to the most common human metabolic disorders, such as obesity, diabetes and NAFLD/NASH.

Systematic Review and Meta-Analysis of the Usefulness of Epicardial Fat Thickness as a Non-Invasive Marker of the Presence and Severity of Nonalcoholic Fatty Liver Disease.

We performed a systematic review and meta-analysis to assess the association between epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD). This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) and was based on a registered protocol (CRD 4201809 5493). We searched Medline and Embase until December 2021 for studies reporting on the association between EFT and NAFLD. Qualitative reviews, meta-analyses and meta-regressions were performed to explore this association. Effect sizes are reported as standardized mean differences. We included 12 studies, comprising 3610 individuals. EFT was evaluated with trans-thoracic echocardiography in nine studies, two studies using cardiac computed tomography and one study using magnetic resonance imaging (MRI). The presence of NAFLD was evaluated using transabdominal liver ultrasound in nine studies. Other studies used histology, magnetic resonance spectroscopy and MRI-derived proton density fat fraction. Liver biopsy was performed to assess the severity of NAFLD in four studies. The random-effects meta-analysis indicated that, as compared to control patients with lean livers, patients with NAFLD displayed significantly higher EFT (standardized mean difference 0.61, 95% confidence interval: 0.47−0.75, p < 0.0001, I2 = 72%). EFT was further significantly higher in patients with severe liver steatosis versus patients with mild−moderate liver steatosis (standardized mean difference 1.21 95% confidence interval: 0.26−2.16, p < 0.001, I2 S = 96%). Through the meta-regression analysis, we found that patients with increasingly higher blood levels of aspartate aminotransferase displayed an increasingly higher depth of association. The current meta-analysis suggests that EFT may represent a useful surrogate for assessing the presence and severity of NAFLD in a non-invasive manner.

Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

Effectiveness of Therapeutic Patient Education Interventions in Obesity and Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis present a critical synthesis of the development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus qualitatively synthesized. Out of these, 47 were included in the quantitative synthesis. There was substantial heterogeneity in the reporting of these outcomes (I2 = 88.35%, Q = 317.64), with a significant improvement noted in serum HbA1c levels (standardized mean difference (SMD) = 0.272, 95% CI: 0.118 to 0.525, n = 7360) and body weight (SMD = 0.526, 95% CI: 0.205 to 0.846, n = 1082) in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (p < 0.001). These interventions should be implemented in healthcare and community settings to improve the health outcomes in patients suffering from obesity and DM.

Cardiovascular outcomes trials: a paradigm shift in the current management of type 2 diabetes.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes (T2D). Historical concerns about cardiovascular (CV) risks associated with certain glucose-lowering medications gave rise to the introduction of cardiovascular outcomes trials (CVOTs). Initially implemented to help monitor the CV safety of glucose-lowering drugs in patients with T2D, who either had established CVD or were at high risk of CVD, data that emerged from some of these trials started to show benefits. Alongside the anticipated CV safety of many of these agents, evidence for certain sodium-glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revealed potential cardioprotective effects in patients with T2D who are at high risk of CVD events. Reductions in 3-point major adverse CV events (3P-MACE) and CV death have been noted in some of these CVOTs, with additional benefits including reduced risks of hospitalisation for heart failure, progression of renal disease, and all-cause mortality. These new data are leading to a paradigm shift in the current management of T2D, with international guidelines now prioritising SGLT2 inhibitors and/or GLP-1 RAs in certain patient populations. However, clinicians are faced with a large volume of CVOT data when seeking to use this evidence base to bring opportunities to improve CV, heart failure and renal outcomes, and even reduce mortality, in their patients with T2D. The aim of this review is to provide an in-depth summary of CVOT data-crystallising the key findings, from safety to efficacy-and to offer a practical perspective for physicians. Finally, we discuss the next steps for the post-CVOT era, with ongoing studies that may further transform clinical practice and improve outcomes for people with T2D, heart failure or renal disease.