Risultati per: Efficacia e sicurezza dei farmaci GLP-1 per il diabete di tipo 2 e l’obesità

Sitd, crescita fenomeni preoccupa soprattutto tra i giovani

Medicinali più consumati sono per cuore, intestino e sangue

Cherubini (Siedp) “evitabili in oltre 450 bimbi ogni anno”

We appreciate the constructive dialogue from Cheng on our study’s findings.1 We agree that any clinical database study has limitations that necessitate careful interpretation of results. Manual medical records review is a logical next step to mitigate these shortcomings and allow a more thorough examination of each patient’s course. Nevertheless, we re-analysed our data in response to points raised. The analyses in our original paper suggest an elevated risk of undergoing an esophagogastroduodenoscopy (EGD) in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA) compared with control. As mentioned in our prior reply,2 we recognise that there is a potential diagnostic bias from this observation. We re-ran our cohorts and found that the rate of undergoing an EGD in the propensity-score matched cohort receiving short-acting GLP-1 RA was 6.13% compared with 5.22% in the matched control cohort (OR 1.185; 95% CI 1.131 to 1.241), reflecting the…

Circulation, Volume 150, Issue Suppl_1, Page A4133830-A4133830, November 12, 2024. Introduction:Combination therapy with SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1RA) reduces major cardiovascular events (MACE) and improves HbA1c, blood pressure, weight, and renal disease progression. The European Society of Cardiology recommends this therapy for ASCVD and T2DM, independent of HbA1c. This study evaluates prescribing patterns in the Internal Medicine Residency Clinics for patients with ASCVD and T2DM.Aims:To investigate demographic and social determinants of health (SDOH) influencing the prescription of combination therapy versus no therapy in an outpatient population and identify factors affecting prescribing patterns and guideline adherence.Methods:We reviewed 828 electronic records of T2DM and ASCVD patients from March 2024. Patients were grouped into combination therapy (SGLT2i and GLP1RA) and no therapy groups. Data on demographics (Table 1) and SDOH (Table 2) were analyzed. Patients on monotherapy or those who did not complete the SDOH questionnaire were excluded. Descriptive statistics were used to summarize demographics. Welch’s t-test compared continuous variables, and chi-square or Fisher’s exact tests compared categorical variables. Analyses were done with SAS 9.4 with significance at 0.05.Results:Age significantly differed between groups (t = 4.56, p < .05), with older patients less likely to receive therapy. Sex was also significant (p < .05); more females were in the no therapy group. No significant association was found between SDOH and combination therapy (p > .05).Conclusion:Over 90% of patients with T2DM and ASCVD were not on optimal medical therapy to reduce MACE, with nearly half on no medications. This highlights the need for increased awareness and targeted interventions to improve outcomes. Future research will explore insurance status and physician awareness to address prescription discrepancies.Limitations:Patients with a GFR

Circulation, Volume 150, Issue Suppl_1, Page A4134267-A4134267, November 12, 2024. Background:The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2is) on reducing cardiovascular events in heart failure patients are well-established; however, less is known about their effects after a myocardial infarction. This study aims to investigate the effects of GLP-1RAs and SGLT2is on in-hospital mortality and 30-day readmission in type 2 diabetic patients with/without heart failure who were hospitalized for acute coronary syndrome (ACS).Methods:We conducted a multicenter retrospective cohort on type 2 diabetic patients who were admitted to the hospital for ACS from 01/01/2020 to 01/31/2024 across 16 West Florida hospitals. Patients receiving a GLP-1RA alone, SGLT2i alone, or both were compared to those taking neither. Chi-square and binary logistic regression were used to predict the clinical outcomes of in-hospital mortality, all-cause readmission within 30 days, and cardiac readmission within 30 days.Results:Among 7,481 type 2 diabetics with ACS, 392 (5.24%) were taking GLP-1RA monotherapy, 577 (7.71%) were taking SGLT2i monotherapy, 144 (1.92%) were taking both, and 6,362 (85.12%) were taking neither. The likelihood of in-hospital mortality was similar among patients on neither medication compared to patients on both (χ2= 0.06,p= 0.802), GLP-1RA monotherapy (χ2= 0.61,p= 0.435), and SGLT2i monotherapy (χ2= 0.002,p= 0.968). The odds of all-cause readmission within 30 days was similar among patients on neither medication compared to patients on both (χ2= 0.0004,p= 0.983), GLP-1RAs monotherapy (χ2= 0.07,p= 0.791), and SGLT2i monotherapy (χ2= 3.10,p= 0.078). The likelihood of cardiac readmission within 30 days was similar among patients on neither medication compared to patients on both medications (χ2= 1.63,p= 0.202), GLP-1RA monotherapy (χ2= 0.95,p= 0.329), and SGLT2i monotherapy (χ2= 0.94,p= 0.332).Conclusion:Our study found no significant differences in the odds of in-hospital mortality or 30-day readmission among type 2 diabetics with ACS who were taking GLP-1RAs, SGLT2is, or both, when compared to those taking neither. These findings further support the outcomes discovered in the EMPACT-MI trial.

Circulation, Volume 150, Issue Suppl_1, Page A4145988-A4145988, November 12, 2024. Introduction:Cardiovascular-kidney-metabolic (CKM) syndrome disproportionately affects individuals with adverse social determinants of health (SDOH). While glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve outcomes in CKM syndrome, inequitable access (e.g., coverage, supply constraints) may worsen health disparities in CKM syndrome.Aims:To characterize the association of individual- and community-level SDOH with GLP-1RA use among Medicare beneficiaries with diabetes.Methods:Cross-sectional study using 100% Medicare claims linked with the Social Vulnerability Index and the US Department of Agriculture Rural-Urban Commuting Area Codes. We evaluated Medicare Advantage and fee-for-service beneficiaries ≥65 years with diabetes enrolled in Part D in 2021 (last year available). Filled prescriptions for GLP-1RAs were identified using National Drug Codes. Baseline characteristics were compared using standardized mean differences. Associations between SDOH (self-identified race and ethnicity, insurance status, social vulnerability index, median household income, rurality, US census region) and GLP-1RA use was evaluated using multivariate logistic regression adjusted for age, sex, and clinical characteristics.Results:Of 13,429,963 adults with diabetes included in the analysis, mean age was 77y and 54.6% were female. During the 1-year study period, 8.5% (475,719) filled ≥1 GLP-1RA prescriptions and were more likely to be younger, have obesity and chronic kidney disease. After adjustment, race and ethnicity were associated with GLP-1 RA use (Compared with non-Hispanic pregnancy: Black race, OR 0.74 (95% CI: 0.73– 0.75); Asian American race, OR 0.80 (0.78– 0.81); Native American, OR, 1.56 (1.50 –1.62); and Hispanic ethnicity 0.91 (0.89–0.93). Medicare Advantage enrollees had lower odds of use than fee-for-service Medicare: OR, 1.18 (1.17 – 1.19). Dual enrollee status, higher median household income, rurality, and higher social vulnerability were associated with greater use.Conclusions:There is substantial variability in the use of GLP-1RAs by individual-level and community-level SDOH factors. Determining the drivers of differential access is urgently needed to enhance equitable use.

Circulation, Volume 150, Issue Suppl_1, Page A4138604-A4138604, November 12, 2024. Introduction:Atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Glucagon-like peptide-1 (GLP-1) agonists have been shown to reduce cardiovascular risk in patients with obesity and diabetes, respectively. Meta-analysis of prospective trials looking at GLP-1 agonist use on the incidence of AF suggest benefit in patients with diabetes but is of unclear benefit in this regard for patients with obesity.Hypothesis:GLP-1 agonists reduce atrial fibrillation incidence in patients with diabetes and obesity.Aims:The goal of the study is to assess the effects of GLP-1 agonist on incidence of new AF in patients with obesity and diabetes following heart failure hospitalization.Methods:The study included consecutive patients who were admitted to an academic tertiary care center over three years with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was incidence of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiography, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new-onset AF following HF hospitalization.Results:Of the patients included in our study, 1668 (42.9%) have a BMI greater than or equal to 30, 574 (14.5%) have BMI greater than or equal to 40, and 2300 (58.2%) have diabetes mellitus. GLP-1 use is associated with a significantly lower incidence of AF at one year in obese patients (p=0.042; RR 0.73; 95% CI: 0.54-.99) (Figure), while in non-obese individuals, GLP-1 receptor agonist was not associated with a decreased incidence of AF (p=0.674; RR 1.08; 95% CI: 0.76-1.53). In patients with diabetes, GLP-1 receptor agonist use did not reach statistical significance for reduced AF incidence following heart failure hospitalization (p=0.091; RR 0.80; 95% CI 0.62-1.04).Conclusion:GLP-1 receptor agonist use is associated with a statistically significant reduction of incidence of new atrial fibrillation at one year following hospitalization for heart failure in obese patients.

Circulation, Volume 150, Issue Suppl_1, Page A4126158-A4126158, November 12, 2024. Introduction:Studies have shown the reduction of CV events in patients with T2D treated with GLP-1 RAs. However, little is known about how persistent use of GLP-1 RA therapy affects CV outcomes in patients with T2D and ASCVD. The objective of this study was to estimate the association between persistent use of once weekly (OW) GLP-1 RAs and 2-point MACE and its components (MI, stroke) in patients with T2D and ASCVD in a real-world setting.Methods:Adult patients with T2D and ASCVD with ≥1 pharmacy claim for OW GLP-1 RAs during Jan 2018-Nov 2022 were identified in the Optum Research Database. The date of the first OW GLP-1 RA claim was defined as the index date. Patients were followed until a CV event occurred or censored. Discontinuation was defined as a ≥60-day gap in supply of OW GLP-1 RAs. All patients were required to be persistent for ≥3 months of follow-up to allow titration of the therapy. CV events of interest include 2-point MACE, MI and stroke. Kaplan-Meier analyses were used to examine risk of CV events by persistent status within 6, 12, or 18 months of follow-up. Cox proportional hazards models with time-varying exposures were used to assess associations between persistent status and MACE, with persistent status of patients updated for each day of follow-up, adjusting for demographic and baseline clinical characteristics.Results:Among a total of 29516 patients, the median follow up duration was 412 days, median persistence was 254 days, and 63.9% of patients (n=18849) were persistent throughout their variable follow up period. Kaplan-Meier analyses indicated risk of 2-point MACE, MI, and stroke was significantly lower in patients who were persistent within 6, 12 or 18 months of follow-up compared to patients who discontinued within 6, 12 or 18 months of follow-up (all p

Circulation, Volume 150, Issue Suppl_1, Page A4139045-A4139045, November 12, 2024. Background:GLP-1 receptor agonists (RA) improve diabetes, reduce cardiovascular events, and cause substantial weight loss. However, concerns have been raised about increased adverse psychiatric effects – namely suicide. Given the explosive increase in use of these agents, detection of even rare side effects is of great clinical importance. We aimed to perform the first meta-analysis of adverse psychiatric outcomes (suicidal ideation/attempt/completion or self-harm) in randomized, placebo-controlled, clinical trials (RCTs) of GLP-1 RA.Methods:A comprehensive literature search through 8/29/23 was conducted to identify RCTs involving adults with diabetes and/or overweight/obesity treated with GLP-1 RA or placebo for ≥6 months. 7,229 non-duplicate articles were screened for inclusion and 144 had data extracted. After querying all available data sources, including direct contact with principal investigators or corresponding authors, 21 of the 144 studies were found to have recorded incidence of adverse psychiatric outcomes. A random-effects meta-analysis was performed to estimate risk ratios and 95% confidence intervals (CI) for the primary outcome.Results:In total, 36,168 subjects received GLP-1 RA and 30,445 placebo. The event rate was very low (63 – GLP-1 RA; 45 – placebo). The pooled odds ratio for incidence of the primary outcome was 0.88 [95% CI, 0.60-1.29]Figure. Notably, 6 studies, including a total of 11,828 subjects, had a history of suicide attempt/depression as exclusion criteria for enrollment. Removal of these studies did not change the overall findings (OR 0.77 [95% CI, 0.38, 1.57]).Conclusion:Our comprehensive meta-analysis of placebo-controlled RCTs does not support an association of GLP-1 RA use with increased adverse psychiatric events among adults with diabetes or overweight/obesity. However, these outcomes were recorded in 1/5 excluded subjects predisposed to these outcomes. More research is necessary, and continued surveillance remains warranted, to establish the safety of GLP-1 RA, particularly in patients at risk for self-harm/suicide.

Circulation, Volume 150, Issue Suppl_1, Page A4145444-A4145444, November 12, 2024. Introduction:Anthracyclines are associated with cancer therapy-related cardiovascular dysfunction and heart failure (HF). The role of GLP-1 receptor agonists for patients with cancer undergoing anthracycline-based chemotherapy remains unknown.Hypothesis:GLP-1 receptor agonists are associated with reduced mortality and cardiovascular events after chemotherapy with anthracyclines.Aims:Evaluate the association between GLP-1-treated patients undergoing chemotherapy with anthracyclines and mortality and cardiovascular events.Methods:We conducted a retrospective cohort study of de-identified, aggregated data from 120 centers using the TriNetX Global Collaborative Network. Patients with ≥18 years old, a diagnosis of cancer, a history of use of anthracyclines, and either type 2 diabetes mellitus or overweight/obesity were included. We excluded patients with end-stage kidney disease, ischemic heart disease, or aortocoronary bypass graft. Patients were stratified according to treatment with GLP-1 receptor agonists or not and underwent propensity score matching. We compared HF exacerbation, hospitalizations or urgent emergency department visits, and all-cause mortality rates using Cox proportional hazard models over an 8-year follow-up.Results:After propensity score matching, 2,575 patients remained in each cohort. At 8 years, GLP-1 use was associated with significantly lower rates of HF exacerbation, defined as the need for diuretics, pulmonary edema, systolic and/or diastolic acute decompensated HF, or reaching a left ventricular ejection fraction

Circulation, Volume 150, Issue Suppl_1, Page A4141989-A4141989, November 12, 2024. Background:Specific sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) significantly improve outcomes in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) or heart failure. Contemporary data regarding utilization rates of these medications remain limited.Hypothesis:Utilization rates of SGLT2i/GLP-1RA remain low, especially among cardiology providers.Aim:Characterize utilization rates of SGLT2i/GLP-1RA in a large academic medical center (AMC).Methods:We developed algorithms to query electronic health records from Beth Israel Deaconess Medical Center to identify 18-74 year-old patients with either T2D and ASCVD (cohort 1) or patients with heart failure with reduced or preserved ejection fraction (HFrEF/HFpEF, cohort 2) who qualified for SGLT2i or GLP-1RA therapy between 1/1/21-12/31/22 according to 2020 ACC Expert Consensus Decision Pathway and 2021 ADA Standards of Care guidelines. Positive predictive values (PPV) for each algorithm were calculated following manual review of 150 randomly-selected charts from each cohort. Comparisons were performed using Fisher’s exact test.Results:We identified 1,022 patients with T2D and ASCVD (PPV 87.9%) who qualified for SGLT2i and/or GLP-1RA therapy and 2,070 patients with HFrEF or HFpEF (PPV 84.7%) who qualified for SGLT2i therapy. In contrast to utilization rates of statins (89.8%), significantly fewer patients with T2D and ASCVD had received a prescription for a SGLT2i (35.9%, P

Circulation, Volume 150, Issue Suppl_1, Page A4144048-A4144048, November 12, 2024. Background:Heart failure (HF) and paroxysmal atrial fibrillation (AF) are major causes of morbidity and mortality, each exacerbating the other and leading to poorer outcomes. Glucagon-like peptide-1 agonists (GLP-1a), primarily used for glycemic control in type 2 diabetes, may offer cardiovascular benefits in patients with concurrent HF and paroxysmal AF.Objective:This study aims to evaluate the impact of GLP-1a on clinical outcomes in patients with concurrent HF and paroxysmal AF.Methods:This retrospective study utilized data from 51,446 HFrEF patients across 91 global healthcare organizations between January 2014 and August 2023. Propensity score matching (PSM) analysis was used to compare cardiovascular outcomes such as all-cause mortality, the need for new antiarrhythmic medication, cardioversion, AF ablation, incidence of acute myocardial infarction (AMI), and cardiac arrest, between those treated with GLP-1a and those who were not.Results:Our analysis revealed that the GLP-1a group had significantly lower odds of requiring cardioversion (3.1% vs 5.0%, OR = 0.67, 95% CI: 0.45–0.99, p=0.041), AF ablation (1.7% vs 3.7%, OR = 0.51, 95% CI: 0.27–0.98, p=0.038), new antiarrhythmic drugs (12.0% vs 13.9%, OR = 0.81, 95% CI: 0.66–0.99, p=0.036), experiencing AMI (OR: 0.70, 95% CI: 0.50–0.98, p=0.035), experiencing cardiac arrest (OR: 0.54, 95% CI: 0.37–0.80, p=0.002), and all-cause mortality (OR: 0.59, 95% CI: 0.51–0.68, p

Circulation, Volume 150, Issue Suppl_1, Page A4142589-A4142589, November 12, 2024. Background:GLP-1 receptor agonists (GLP1RA) agonists have been shown to reduce cardiovascular events in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, it is unclear whether early subclinical therapeutic changes can be detected from routine 12-lead electrocardiograms (ECGs).Methods:We finetuned a neural network (NN) from Pheiron’s phenotyping platform to predict subclinical risk markers from 12-lead ECGs using data from Dandelion Health, comprised of longitudinal, multimodal real-world clinical data for 106,289 patients receiving care from Sharp Healthcare in the US. Based on the finetuned NN, we predicted risk markers within an independent cohort of 48,376 patients with a history of T2D, ASCVD, or obesity and emulated a target trial to evaluate the subclinical effect of GLP1RA. The primary analysis compared percentile rank transformed ECG markers for GLP1RA and non-GLP1RA patients using inverse probability weighted (IPW) linear regression models, adjusted for key variables including demographics, comorbidities, medications, HbA1c, and BMI at baseline. Sensitivity analyses included unadjusted models, models with only covariate adjustments, and propensity score-matched models.Results:The emulated trial study cohort was, on average, 59.6 [SD 15.9] years old, predominantly female (56%), and racially diverse: 46.6% White, 25.3% Hispanic, 9.6% Asian, and 4.6% Black. Compared to the control group, the GLP1RA cohort had a higher baseline risk profile (BMI: 35.1 [SD 7.6] vs. 31.0 [SD 6.0], HbA1c: 7.1 % [SD 1.8] vs. 5.8 % [SD 0.9]) but cardiovascular risk progressed slower during the observation time: Each year of GLP1RA treatment was linked to percentile risk reductions of -1.65 (p

Circulation, Volume 150, Issue Suppl_1, Page A4140511-A4140511, November 12, 2024. BACKGROUND:Atrial natriuretic peptide (ANP) and glucagon-like peptide-1 (GLP-1) are endogenous hormones known for roles in cardiovascular regulation and metabolic homeostasis. ANP mediates its actions via the GC-A receptor, while GLP-1 via the GLP-1 receptor (GLP-1R). Both peptides may stimulate insulin secretion from pancreatic beta cells and augment lipid metabolism in adipocytes, yet potential synergistic effects remain unexplored. To optimize ANP activation of GC-A, we developed a novel 15 amino acid miniaturized GC-A activating peptide CRRL555. CRRL555 possesses greater GC-A binding and activating properties than ANP.AIMS:We investigated the metabolic properties of CRRL555/GC-A and its interaction with GLP-1/GLP-1R in vitro.METHODS:Rat pancreatic beta cells (INS-1) were stimulated with high glucose (20mM) and treated with GLP-1 or CRRL555 (10-10-10-6M) and together for 1 hr. Supernatant was collected and insulin was measured by ELISA. Human visceral adipocytes were differentiated for 10 days and then treated with GLP-1 or CRRL555 (10-10-10-6M) or together for 6 hrs. Supernatant was collected and glycerol and free fatty acid (NEFA), indicators of lipolysis, were measured.RESULTS:CRRL555 (p

Circulation, Volume 150, Issue Suppl_1, Page A4139502-A4139502, November 12, 2024. Background:Semaglutide reduced 5-year rates of coronary revascularization by 23% in SELECT. The impact of broader adoption of glucagon-like peptide 1 (GLP-1) agonists on coronary stent use among elderly patients with cardiovascular (CV) disease is unclear.Methods:To project the impact of GLP-1 adoption on 5-year rates of coronary stent use, we analyzed claims data for the 5% random sample of fee-for-service Medicare and Medicare Advantage beneficiaries identified in 2016 (n=1,847,213). Patient risk for CV events was derived using the REGARDS study administrative CV risk algorithm. Five-year observed coronary stent use was based on treatment in 2017–21. The unadjusted association between derived CV event risk and observed stent use was modeled as a flexible linear spline. Projected impact of increased GLP-1 use on patients’ 5-year risk of stent use was calculated by applying SELECT estimates of coronary revascularization reduction (HR 0.77 95% CI 0.68–0.87) to patients’ REGARDS-derived CV event risk and estimating stent use at the GLP-1-driven reduced derived CV event risk level. We projected impact on 5-year stent use as GLP-1 use increased from 0% to 100% of beneficiaries under 4 CV risk-based adoption scenarios: highest CV risk first; lowest CV risk first; median CV risk patients first (base case); and random adoption.Results:Sixty percent adoption of GLP-1 (current statin use) by median CV risk patients first would reduce coronary stent use overall by 6.9% (95% CI 3.6%–9.8%). Impact varied by role of CV risk in GLP-1 adoption, with 60% use in highest CV risk patients first resulting in 21.5% (95% CI 14.3%–25.8%) reduction as opposed to 5.9% (95% CI 3.3%–8.3%) if driven by population with 60% lowest CV risk (Figure). Adoption by 25% highest CV risk would achieve 70% benefit of complete population use. Reductions varied more than two-fold across hospital referral regions (HRRs) in the base case, ranging from 4.5% (95% CI 2.4%–6.1%) to 9.2% (95% CI 4.7%–13.3%); the highest CV-risk-first approach impact ranged from 13.6% (95% CI 9.0%–16.8%) to 30.7% (95% CI 20.7%–35.6%).Conclusion:GLP-1 adoption by Medicare beneficiaries comparable to current statin use could reduce coronary stent use nationally by 6.9% if focused on median CV risk, but up to 21.5% if focused on highest CV risk patients first. Impact varies by HRR, with high GLP-1 use among highest CV risk patients reducing stent use as much as >30%.