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According to their selectivity for sodium-glucose cotransporters (SGLT) 1 and 2, gliflozins could be subdivided into two additional categories: pure SGLT2 inhibitors, which are highly selective for SGLT2, and dual SGLT1/2 inhibitors which, in addition to SGLT2, exhibit strong inhibitory activity for SGLT1.This article aims to discuss whether the pharmacological differences between the two subtypes of gliflozins could be translated into different efficacy and safety characteristics that might be important for clinical practice.In large cardiovascular outcome trials, dual inhibitors have shown a unique efficacy profile in terms of reducing glycemia in patients with severe renal impairment and decreasing the risk of atherosclerotic outcomes. These features do not characterize selective SGLT2 inhibitors and could be attributed to the parallel inhibition of SGLT1. The increased risk of diarrhea and severe hypoglycemia observed only with dual inhibitors is probably related to their action in the gut and brain, respectively. However, differences in populations included in various studies should be considered when attempting to translate their findings into clinical practice; therefore, head-to-head trials are needed to shed more light on this issue and provide clear guidance to clinicians.

The management of hyperglycemia in patients admitted to hospital is mainly based on insulin therapy. However, the positive and rapid effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiorenal outcomes raises the possibility that they might confer benefits to hospitalized patients. In recent, well designed, randomized trials (SOLOIST-WHF and EMPULSE) recruiting inpatients with heart failure (HF), SGLT2i demonstrated the potential to improve survival and quality of life and reduce the number of HF events, time to first HF event, hospitalizations, and urgent visits for HF compared with placebo. They were also well tolerated, whereas incidence of diabetic ketoacidosis was low. In EMBODY, empagliflozin was shown to be protective against the deleterious effects of cardiac injury in patients with acute myocardial infarction. In DARE-19, the administration of dapagliflozin to inpatients with cardiometabolic risk factors and COVID-19 was based on the hypothesis that the anti-inflammatory properties of SGLT2i could alleviate organ damage. Although the findings did not reach statistical significance, the efficacy and safety profiles of the drug were encouraging. These promising findings in the field of cardiometabolic medicine set the stage for future research to explore whether the benefits of gliflozins can expand to inpatients with non-cardiometabolic disorders, including sepsis, cirrhotic ascites, and malignancies. The concept of inpatient use of SGLT2i has evolved greatly over the past few years. The latest evidence suggests that SGLT2i may be effective and safe in the hospital setting, provided patients are carefully selected and closely monitored. Real-world data will prove whether present hope about inpatient use of gliflozins will transform into future confidence.

Objective The efficacy of renal sympathetic denervation (RDN) has been affirmed by a number of recent clinical studies, despite controversies in this field over the last five years. Therefore, it is of paramount importance that hypertension experts debate the merits of RDN by revealing and expressing their personal beliefs and perspectives regarding this procedure. Methods A cross-sectional survey was conducted among Greek leaders of the Hypertension Excellence Centers with the use of a closed-type questionnaire specifically designed to elicit information and evaluate the respondent's views and perspectives about RDN efficacy, safety and ideal target patient population. Results A total of 36 participants completed the survey. Based on the results, RDN was considered efficient (91.7%) and safe (94.5%), while the overwhelming majority of the participants felt confident in the long-term efficacy (88.9%) of the intervention and that it lacks reliable predictors of blood pressure response (94.5%). Patients with resistant (91.7%), ultra-resistant (94.4%), and uncontrolled hypertension (80.6%) were suggested as ideal candidates for RDN. Establishing a close co-operation between interventionalists and hypertension experts was considered essential to ensure the efficacy (97.2%) as well as the safety (97.3%) of the procedure. Conclusion The vast majority of Greek hypertension experts surveyed were convinced of the efficacy and safety of RDN based on the preponderance of available scientific and clinical data. Identification of the ideal patient group remains controversial. Respondents generally agreed on the necessity of building close collaborative relationships between interventionalists and hypertension experts in order to improve RDN clinical outcome.

Hypertension remains a major public health issue with inadequate control worldwide. The May Measurement Month (MMM) initiative by the International Society of Hypertension was implemented in Greece in 2019 aiming to raise hypertension awareness and control. Adult volunteers (≥18 years) were recruited through opportunistic screening in five urban areas. Information on medical history and triplicate sitting blood pressure (BP) measurements were obtained using validated automated upper-arm devices. Hypertension was defined as systolic BP ≥140 mmHg and/or diastolic ≥90 mmHg, and/or self-reported use of drugs for hypertension. A total of 5727 were analysed [mean age 52.7 (SD 16.6) years, men 46.5%, 88.3% had BP measurement in the last 18 months]. The prevalence of hypertension was (41.6%) and was higher in men and in older individuals. Among individuals with hypertension, 78.7% were diagnosed, 73.1% treated, and 48.3% controlled. Awareness, treatment, and control of hypertension were higher in women and in older individuals. Hypertensives had a higher body mass index (BMI) and were more likely to have diabetes, myocardial infarction and stroke, and less likely to smoke than normotensives (all P

This study aimed to assess the reliability of opportunistic screening programs in estimating the prevalence, treatment, and control rate of hypertension in the general population. Two recent epidemiological surveys obtained data on hypertension in the adult general population in Greece. The EMENO (2013–2016) applied a multi-stage stratified random sampling method to collect nationwide data. The MMM (2019) collected data through opportunistic (voluntary) screening in five large cities. Hypertension was defined as blood pressure (BP) ≥ 140/90 mmHg (single occasion; average of 2nd–3rd measurement; electronic devices) and/or use of antihypertensive drugs. Data from a total of 10,426 adults were analyzed (EMENO 4,699; MMM 5,727). Mean age (SD) was 49.2 (18.6)/52.7 (16.6) years (EMENO/MMM, p

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence and a significant burden of long-term complications. Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) are a novel treatment option for T2DM, exerting optimal effects on glucose control and weight loss, and pleiotropic actions. Pharmacogenetics, a promising research field of precision medicine, investigates how gene variations can affect individual response to drug therapy, assuming that the diverse genetic architecture of patients with T2DM could be partly associated with the considerable inter-individual variability in the therapeutic response to GLP-1 RAs. This review aims to summarize current evidence related to T2DM risk variants, affecting the incretin pathway, focus on the pharmacogenetics of the GLP-1 RA liraglutide, and discuss their potential clinical implications in the management of this complex disorder. Methods: A literature search was performed using electronic biomedical databases, and the findings of key studies are summarized and discussed in this narrative review. Results: Available evidence suggests the involvement of genetic polymorphisms in GLP-1 Rgene in variation in glycemic response, metabolic parameters and gastric emptying in people treated with liraglutide. Polymorphisms in CNR1, CTRB1/2, TMEM114 and CHST3 loci were also shown to be implicated in the disturbance of the incretin homeostasis in T2DM. These findings warrant further investigation by future studies. Conclusion: Robust findings from pharmacogenetic studies might be used to identify good responders to liraglutide treatment, in terms of both glycemic and weight control, thus reinforcing the patient-centered approach of T2DM management.

Prior studies have associated automated peritoneal dialysis (APD) with less effective volume and blood pressure (BP) control as compared with continuous ambulatory peritoneal dialysis (CAPD). Our study aimed to compare the volume status, ambulatory BP profile and severity of arterial stiffness between patients treated with CAPD versus APD. In a case-control design, 28 CAPD patients were matched in 1:1 ratio with 28 controls receiving APD for age, gender and diabetic status. Body composition was assessed with the method of bioimpendence spectroscopy. Twenty-four hours ambulatory BP monitoring with the Mobil-O-Graph device (IEM, Germany) was performed to determine peripheral and central hemodynamic parameters, heart rate-adjusted augmentation index (AIx75) and pulse wave velocity (PWV). Standardized office BP, antihypertensive medication use and extracellular-to-total body water ratio did not differ between CAPD and APD groups. Twenty-four hours brachial systolic BP (129.0 ± 17.3 vs. 128.1 ± 14.2 mmHg, P = 0.83) and 24-h aortic systolic BP (116.9 ± 16.4 vs. 116.4 ± 11.6 mmHg, P = 0.87) were similar in patients treated with CAPD versus APD. Similarly, there was no significant difference between PD modalities in severity of arterial stiffness, as assessed with 24-h AIx75 (24.8 ± 8.9 vs. 22.5 ± 9.1, P = 0.36) and 24-h PWV (9.1 ± 2.4 vs. 8.8 ± 2.1 m/s, P = 0.61). The present study suggests that there is no difference in peripheral and central hemodynamic parameters as well as in the severity of arterial stiffness between CAPD and APD. However, these observations should be interpreted within the context of clinical characteristics of patients included in this case-control study. The comparative effectiveness of these 2 PD modalities warrants further investigation in larger longitudinal studies.

Emerging data are linking coronavirus disease 2019 (COVID‐19) with an increased risk of developing new‐onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID‐19‐induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium‐glucose co‐transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium‐dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID‐19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID‐19 outweigh potential risks, particularly with respect to drug‐induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

BACKGROUND AND AIMS Assessment of dry-weight among patients on haemodialysis is challenging in the absence of reliable markers to define overhydration (OH) [1, 2]. This study aimed to explore the value of two simple clinical signs, the presence of pedal oedema and crackles at pulmonary auscultation, in diagnosing hypervolemia, using the bioimpendence spectroscopy as a more objective method. METHOD In a cohort of 107 asymptomatic dialysis patients, the volume status was assessed with physical examination and bioimpedance spectroscopy shortly before the mid-week dialysis session [3]. Patients were also asked to perform home blood pressure (BP) monitoring with a validated, automatic device (HEM-705, Omron, Healthcare) [4] for 1 week in order to determine their BP control status. RESULTS Patients within the high tertile of pre-dialysis OH had longer dialysis vintage, lower serum albumin and higher home systolic BP, despite the more aggressive treatment with a higher average number of antihypertensives daily. In receiver-operating-characteristic (ROC) curve analysis, pedal oedema [area under curve (AUC): 0.534, 95% confidence interval (95% CI) 0.416–0.651] and pulmonary crackles (AUC: 0.551; 95% CI 0.432–0.671) had limited accuracy in the diagnosis of pre-dialysis OH > 2.2 L. The agreement of pedal oedema (Cohen's k-coefficient: 0.065) and pulmonary crackles (Cohen's k-coefficient: 0.122) with bioimpedance spectroscopy in the detection of hypervolemia was poor. In multivariate linear regression analysis, longer dialysis vintage (β: 0.306; P CONCLUSION This diagnostic-test study showed that among asymptomatic hemodialysis patients, pedal oedema and pulmonary crackles in physical examination had limited discriminatory power in the detection of hypevolemia, as assessed more objectively with the method of bioimpedance spectroscopy.

BACKGROUND AND AIMS During the coronavirus disease-2019 (COVID-19) pandemic, the National Healthcare System of Greece was reorganized in order to cover the expected rise in hospitalizations of critically ill patients with COVID-19 infection. Accordingly, the aim of the present study was to explore whether the onset of the pandemic influenced the hospitalization rate of patients with end-stage kidney disease (ESKD) in a large tertiary university hospital in the metropolitan region of Thessaloniki, Greece. METHOD In this observational study, we retrospectively collected data regarding the hospitalizations of ESKD patients in the section of Nephrology of the first Department of Internal Medicine at the AHEPA University Hospital of Thessaloniki. We provide a comparative evaluation of the number of hospitalizations, demographic characteristics of patients and in-hospital outcomes between the 1-year-long period before (1 March 2019–29 February 2020) and the corresponding period after the onset of the COVID-19 pandemic (1 March 2020–28 February 2021). RESULTS Over the 1-year period before the onset of the pandemic, 149 ESKD patients with various complications were hospitalized in our department. During the control period, we recorded only 90 non-COVID-19 hospitalizations of ESKD patients (Table 1). There was no significant difference in the age and gender of patients who were hospitalized before and after the onset of the pandemic. Furthermore, the median duration of hospitalizations and the in-hospital mortality rate were comparable between the two periods. Over the 1-year-long period after the onset of the pandemic, our department provided care to 50 ESKD patients (32 males and 18 females) with COVID-19 infection who had a mean age of 66.3 ± 16.1 years. Of these, 33 patients (66%) were given discharge from the hospital, and the remaining 17 patients (34%) died. CONCLUSION This single-centre observational study shows a significant reduction in non-COVID-19 hospitalizations of ESKD patients in a tertiary University Hospital of Thessaloniki after the onset of the pandemic. However, the demographic characteristics of patients who were hospitalized, the duration of in-hospital care and clinical outcomes were comparable between the pandemic and control periods.

BACKGROUND AND AIMS Prospective cohort studies have shown that among patients on haemodialysis, hyperkalaemia is strongly associated with excess risk for cardiovascular-related hospitalizations and sudden cardiac death [1–4]. However, the actual burden of hyperkalaemia, the rates of its recurrence and seasonality in its variation still remain unclear. METHOD Between June 2020 and May 2021, 1786 mid-week predialysis serum potassium (sK) measurements were retrospectively recorded from 149 patients receiving thrice-weekly haemodialysis in a single-centre in Thessaloniki, Greece. The prevalence, recurrence and seasonal variation of hyperkalaemia were assessed using three prespecified sK thresholds (≥5.1, ≥5.5 and ≥ 6.0 mmol/L). RESULTS At baseline (June 2020), 60.4%, 42.2% and 13.4% of patients had sK levels ≥ 5.1, ≥5.5 and ≥ 6.0 mmol/L, respectively. At any time-point during the 1-year-long follow-up, 85.2%, 69.8% and 38.9% of patients experienced at least 1 hyperkalaemic episode at the sK threshold of ≥ 5.1, ≥5.5 and ≥ 6.0 mmol/L, respectively. Of the 104 patients experiencing an initial sK elevation ≥ 5.5 mmol/L, hyperkalaemia at the same threshold reoccurred in 60.6% at month-1, in 47.1% at month-2 and in 46.1% at month-3 of follow-up. Seasonal variation was also observed, with the prevalence of hyperkalaemia to be significantly higher in summer. In multivariate logistic regression analysis, shorter delivered haemodialysis CONCLUSION The present study shows that among patients receiving conventional thrice-weekly haemodialysis, the rates of hyperkalaemia prevalence and recurrence are very high, reflecting the large unmet need to identify more effective potassium-lowering therapeutic interventions in this high-risk population.

BACKGROUND AND AIMS Hypertension among patients on long-term peritoneal dialysis (PD) is common and remains often inadequately control (Cocchi et al. Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study. Nephrol Dial Transplant. 1999; 14(6): 1536–40; Vaios et al.. Assessment and management of hypertension among patients on peritoneal dialysis. Clin J Am Soc Nephrol. 2019; 14(2): 297–305). The aim of the present study was to describe the epidemiology of hypertension using the ‘gold-standard’ method of ambulatory blood pressure monitoring (ABPM) and to identify determinants of inadequate ambulatory blood pressure (BP) control in this high-risk population. METHOD In 140 stable patients receiving PD in four centers of Northern Greece, we performed 24-h ABPM using the oscillometric Mobil-O-Graph device (IEM, Stolberg Germany) (Franssen and Imholz. Evaluation of the Mobil-O-Graph new generation ABPM device using the ESH criteria. Blood Press Monit. 2010; 15(4): 229–31). Hypertension was defined as 24-h ambulatory BP ≥ 130/80 mmHg or current use of at least 1 BP-lowering medication (Williams et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018; 36(10): 1953–2041). The volume status of study participants was assessed with the method of bioimpedance spectroscopy (Fresenius Medical Care, Bad Homburg, Germany). Univariate and multivariate binary logistic regression analysis was performed to identify factors that were independently associated with uncontrolled ambulatory hypertension. RESULTS Ambulatory hypertension was diagnosed in 95% of the patients enrolled in the study. Despite the fact that 96.9% of hypertensives were being treated with an average of 2.4 BP-lowering medications daily, adequate control of 24-h ambulatory BP was achieved in only 38.3% of them. In univariate regression analysis, there was a significant interaction of uncontrolled ambulatory hypertension with the mode of PD, history of cardiovascular disease and smoking status. In multivariate analysis, among variables inserted in the model, the higher overhydration index in bioimpedance spectroscopy [odds ratio (OR): 1.308; 95% confidence interval (CI): 1.023–1.673/L higher overhydration] and the history of cardiovascular disease (OR: 3.069; 95% CI: 1.157–8.140) were the two factors that were associated with higher odds of uncontrolled ambulatory hypertension. In contrast, the presence of residual diuresis ≥ 0.5 L/24 h (OR: 0.304; 95% CI: 0.105–0.881) was the only parameter associated with lower odds of inadequate ambulatory BP control. CONCLUSION Among patients on PD, ambulatory hypertension is highly prevalent and remains often poorly controlled, despite the extensive use of antihypertensive drug therapy. Achievement of adequate volume control and long-term preservation of residual kidney function appear to be two attractive non-pharmacological strategies for optimization of the management of hypertension in this high-risk population.

The present study aimed to evaluate the possible consequences of sickle cell disease (SCD) on dental and periodontal health in middle-aged patients and to examine the association of certain cardiovascular parameters and serum ferritin with the dental and periodontal status.Thirty-seven patients (mean age 43.2 years old) with SCD and 30 non-SCD and otherwise healthy individuals (mean age 38.9 years old) were examined for caries experience and periodontal status in addition to cardiovascular characteristics and ferritin level in serum.Compared to controls, SCD patients exhibited higher plaque and gingival bleeding scores, higher prevalence of periodontal diseases, and higher caries experience. Multiple stepwise linear regression analysis showed that caries experience was predominantly determined by the presence of SCD and the age, while major determinants of periodontitis were the ferritin levels and the male gender. The results reveal an aggravation of oral health in SCD patients regarding both caries and periodontal diseases.A potential role of the increased central inflammatory response, reflected by the elevated ferritin level in serum, is suggested for the impaired periodontal health of SCD patients.Compliance with precautionary dental checks and early management of dental complications is of great importance in order to improve oral health status and prevent general health complications in SCD patients.

Background: Among patients with end-stage kidney disease (ESKD), arterial stiffness is considered as a powerful predictor of cardiovascular (CV) morbidity and mortality. However, the relevance of aortic pulse wave velocity (PWV) as a prognostic biomarker for CV risk estimation is not yet fully clear. Methods: We performed a systematic search of Medline/PubMed database from inception through August 21, 2019 to identify observational cohort studies conducted in ESKD patients and exploring the association of PWV with CV events and mortality. Results: Whereas “historical” cohort studies showed aortic PWV to be associated with higher risk of CV and all-cause mortality, recent studies failed to reproduce the independent predictive value of aortic PWV in older ESKD patients. Studies using state-of-the-art prognostic tests showed that the addition of aortic PWV to standard clinical risk scores could only modestly improve CV risk reclassification. Studies associating improvement in PWV in response to blood pressure (BP)-lowering with improvement in survival cannot demonstrate direct cause-and-effect associations due to their observational design and absence of accurate methodology to assess the BP burden. Conclusion: Despite the strong pathophysiological relevance of arterial stiffness as a mediator of CV disease in ESKD, the assessment of aortic PWV for CV risk stratification in this population appears to be of limited value. Whether aortic PWV assessment is valuable in guiding CV risk factor management and whether such a therapeutic approach is translated into improvement in clinical outcomes, is an issue of clinical relevance that warrants investigation in properly-designed randomized trials.

A hypocaloric diet, based on Orthodox fasting (OF) was followed by 29 overweight adults. A low-calorie, 16/8, time restricted eating (TRE) pattern was followed by 16 age- and weight-matched participants. Anthropometric, lipid, glycaemic and inflammation markers were assessed at baseline, at the end of the intervention (7 weeks from baseline) and 6 weeks after the cessation of diets (13 weeks from baseline). There was a trend of weight loss in both groups, which was evident at week 7 (TRE: -2.1 ± 1.0; OF: -2.0 ± 0.5 kg

Background Hyperglycaemia is an ongoing challenge in hospital settings and is associated with poor outcomes. Current recommendations for the management of inpatient hyperglycaemia suggest insulin as the main glucose-lowering treatment choice and limit the administration of oral antidiabetes agents to a small proportion of cases because of safety concerns. Aim To present and critically appraise the available evidence on the use of oral antidiabetes agents in the hospital setting and the risk-benefit balance of such an approach in the era of cardiovascular outcomes trials. Methods PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the efficacy and the safety profile of oral agents in the context of their use in hospitalized individuals are summarized and discussed in this narrative review. Results There is no robust evidence to suggest the use of metformin, thiazolidinediones, sulfonylureas and sodium-glucose co-transporter-2 inhibitors in the hospital setting, although some of their effects on acute outcomes deserve further evaluation in future studies. However, the use of dipeptidyl peptidase-4 inhibitors in inpatients with type 2 diabetes is supported by a few, well-designed, randomized controlled trials. These trials have demonstrated good safety and tolerability profiles, comparable to insulin glucose-lowering efficacy, and a reduction in insulin dose when dipeptidyl peptidase-4 inhibitors are co-administered with insulin, in individuals with mild to moderate hyperglycaemia and a stable clinical condition. Conclusion The administration of dipeptidyl peptidase-4 inhibitors to specific groups of inpatients might be a safe and effective alternative to insulin.

A number of studies have investigated primary and secondary prevention strategies for type 1 diabetes (T1D), since early interventions might improve long-term outcomes through the amelioration of immune processes and the preservation of beta-cell mass. Primary prevention trials focus on genetically at-risk individuals prior to the appearance of autoimmunity, whereas secondary prevention trials aim to halt the progression of complete beta-cell destruction in subjects with established islet autoimmunity (IA). Different approaches have been tested so far, focusing on both pharmaceutical (insulin and monoclonal antibodies) and non-pharmaceutical (vitamin D, omega-3 fatty acids, probiotics, and nicotinamide) interventions, as well as on environmental factors that are believed to trigger autoimmunity in T1D (cow's milk, gluten, and bovine insulin). Albeit certain strategies have displayed efficacy in reducing IA development rates, most efforts have been unsuccessful in preventing the onset of the disease in high-risk individuals. Moreover, significant heterogeneity in study designs, included populations, and explored outcomes renders the interpretation of study results challenging. The aim of this narrative review is to present and critically evaluate primary and secondary prevention strategies for T1D, seeking to fill existing knowledge gaps and providing insight into future directions.

The majority of vascular access thrombosis episodes in hemodialysis patients are due to anatomic abnormalities. Thrombophilias are inherited, acquired or mixed disorders which also predispose to venous thromboembolism. They include protein C, protein S and antithrombin deficiencies, as well as gene mutations for prothrombin and factor V Leiden. The most important of the mixed cases is hyperhomocysteinemia, which includes both a genetic and an acquired substrate. We report two patients undergoing hemodialysis who suffered from multiple thrombotic events, the first due to factor V Leiden heterozygosity and the second because of hyperhomocysteinemia due to homozygosity for MTHFR C677T mutation. As no site for vascular access was left, transfer to peritoneal dialysis for both patients improved solute clearance and quality of life with no additional thrombotic events noted.

The prevalence of gestational diabetes mellitus (GDM) has been following an increasing trend during the past few years, with available epidemiological data suggesting that it affects approximately ...

Background: Evidence suggests a heterogeneous response to therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to identify the genetic and clinical factors that relate to glycemic control and weight loss response to liraglutide among patients with T2DM. Methods: The medical records of 116 adults with T2DM (51% female, mean body mass index 35.4 ± 6.4 kg/m2), who had been on treatment with liraglutide for at least 6 months and were genotyped for CTRB1/2 rs7202877 (T > G) polymorphism, were evaluated. Clinical and laboratory parameters were measured at baseline, 3, and 6 months after initiating liraglutide treatment. The good glycemic response was defined as one of the following: (i) achievement of glycated hemoglobin (HbA1c) < 7% (ii) reduction of the baseline HbA1c by ≥1%, and (iii) maintenance of HbA1c < 7% that a patient already had before switching to liraglutide. Weight loss responders were defined as subjects who lost ≥3% of their baseline weight. Results: Minor allele frequency was 16%. Individuals were classified as glycemic control and weight loss responders (81 (70%) and 77 (66%), respectively). Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.4, 3.8, p = 0.69) and weight loss (OR: 1.12, 95% CI: 0.4, 3.2, p = 0.84). In the multivariable analysis, higher baseline HbA1c (adjusted OR: 1.45, 95% CI: 1.05, 2.1, p = 0.04) and lower baseline weight (adjusted OR: 0.97, 95% CI: 0.94, 0.99, p = 0.01) were associated with better glycemic response to liraglutide, while higher baseline weight was associated with worse weight response (adjusted OR: 0.97, 95% CI: 0.95, 0.99, p = 0.02). Conclusions: Specific patient features can predict glycemic and weight loss response to liraglutide in individuals with T2DM.

Type 2 diabetes mellitus (T2DM) is a progressive disease with a growing prevalence, associated with an increased risk of complications. The introduction of new classes of antidiabetic drugs into clinical practice has dramatically changed the landscape of diabetes therapy. However, despite the progress made in the pharmacotherapy of T2DM, mitigating the burden of the disease on individuals, societies and health care systems remains a challenge. Remission has recently emerged as a therapeutic target in T2DM, achievable through a wide range of interventions. Recent studies have shown that extensive lifestyle changes, such as weight reduction, bariatric surgery, and intensive glucose lowering therapy, can prompt the remission of diabetes, but some unanswered questions remain regarding its long-term effects on diabetic complications. Metabolic surgery and novel classes of glucose-lowering medications are currently the most effective interventions to induce weight loss and by extension remission in patients with diabetes; however, the ideal strategy to achieve the long-term maintenance of remission remains doubtful. In this narrative review, we discuss the available therapeutic approaches to target the remission of diabetes through personalized multimodal care, based on the latest evidence.

Contains fulltext : 286841.pdf (Publisher’s version ) (Closed access) BACKGROUND: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. METHODS: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. FINDINGS: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was -15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, -15·2 (0·9) mm Hg for aprocitentan 25 mg, and -11·5 (0·9) mm Hg for placebo, for a difference versus placebo of -3·8 (1·3) mm Hg (97·5% CI -6·8 to -0·8, p=0·0042) and -3·7 (1·3) mm Hg (-6·7 to -0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was -4·2 mm Hg (95% CI -6·2 to -2·1) and -5·9 mm Hg (-7·9 to -3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p

Introduction Despite the progress made in the treatment of heart failure with reduced ejection fraction (HFrEF) in recent years, the prognosis of the disease remains poor, with ventricular arrhythmias (VA) contributing significantly to increased mortality. Areas covered A recently published post hoc analysis of the DAPA-HF trial evaluated the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin versus placebo on the incidence of VA, resuscitated cardiac arrest, or sudden death among people with HFrEF. During a median follow-up of 18.2 months, the composite primary outcome occurred in 140 (5.9%) people who received dapagliflozin compared to 175 (7.4%) participants in the placebo arm (hazard ratio 0.79; 95 confidence interval 0.63-0.99, P=0.037). Animal studies suggest that SGLT2i could ameliorate the deleterious effects of myocardial injury, through various mechanisms, including reduced sympathetic activity, improved oxidative stress, tissue oxygenation, autophagy, heart energy metabolism, and promotion of cardiac remodeling. Expert opinion Taken together, the above findings indicate a place for SGLT2i in future trials investigating novel treatments to improve survival in patients with acute cardiovascular episodes. This is primarily applicable for acute decompensated HF; however, their use could also be evaluated in other conditions that induce VA, such as acute coronary syndromes.