Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for the treatment of type 2 diabetes and, more recently, for weight management among individuals without diabetes. Aim: This review synthesizes the current evidence on the mechanisms by which GLP-1 RAs affect BP, their clinical effects across populations, and the implications for patient care. We discuss subpopulations who may benefit from their BP-lowering effects, identify limitations in the existing evidence, and explore future directions for research. Results: Beyond their metabolic effects, growing evidence suggests that GLP-1 RAs produce modest reductions in BP, typically 2-5 mm Hg systolic, across diverse populations with diabetes, obesity, or at high cardiovascular risk. These reductions appear to be driven primarily by weight loss, with additional contributions from potential weight-independent mechanisms such as natriuresis, improved endothelial function, and attenuation of vascular inflammation. Although smaller in magnitude than those achieved with traditional antihypertensive drugs, the BP-lowering effects of GLP-1 RAs can translate into meaningful cardiovascular risk reduction at the population level and provide additive BP benefit when used alongside conventional therapies. Among individuals with hypertension, GLP-1 RAs are generally well tolerated, although small increases in heart rate and potential interactions with volume-regulating medications may warrant clinical attention. Conclusion: As newer GLP-based therapies continue to emerge, a clearer understanding of their effects on BP may inform more integrated approaches to cardiometabolic care.

Background: Multiple glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and newer dual/triple co-agonists promote weight loss in adults without diabetes, yet comparative efficacy across agents remains uncertain. Aim: To compare and rank the efficacy of GLP-1 RAs and co-agonists for weight loss using network meta-analysis (NMA). Methods: We searched MEDLINE, EMBASE and Cochrane CENTRAL from inception to May 2025 for randomized controlled trials (RCTs) enrolling adults with overweight/obesity without diabetes. Each agent was analyzed at its highest tested (pre-market) or approved dose. We synthesized relative weight change using a frequentist random-effects NMA at approximately 6 months and 1-1.5 years, and ranked treatments using surface under the cumulative ranking curves (SUCRA; the probability that an agent is the best, scaled 0-1). Results: We identified 25 RCTs (n=15 913) evaluating 11 agents (3 commercially available for weight management [liraglutide, weekly semaglutide, and tirzepatide] and 8 pre-market). At 6 months, all agents significantly reduced weight versus placebo; retatrutide ranked highest (mean difference [MD]: -15.8%, 95% confidence interval [CI] -17.6 to -14.1; SUCRA 1.00), followed by mazdutide (MD: -12.3%, 95% CI -14.1 to -10.5; SUCRA 0.89) and orforglipron (MD: -10.6%, 95% CI -12.8 to -8.4; SUCRA 0.75). Among the commercially available agents, tirzepatide ranked highest (MD: -9.6%, 95% CI -10.1 to -9.1; SUCRA 0.64). No head-to-head trials were available at this timepoint, so all active-to-active estimates were indirect. At 1-1.5 years, retatrutide remained top-ranked (SUCRA 0.99) and outperformed all currently marketed agents, achieving 3.2% greater weight loss than tirzepatide (95% CI -0.4 to 6.8; SUCRA 0.86), 9.9% more than weekly semaglutide (95% CI 6.5 to 13.3; SUCRA 0.47), and 17.2% more than liraglutide (95% CI 13.8 to 20.7; SUCRA 0.14). Conclusions: Among adults without diabetes, dual- and triple-agonists, particularly tirzepatide and retatrutide, achieve the greatest weight reductions, while conventional single GLP-1 RAs yield smaller effects. These findings can guide clinicians and policymakers as novel agents progress toward regulatory approval.

The goal of maintenance of certification (MOC) activities is to ensure physicians are up to date on current practices and demonstrate the knowledge and skills required to provide patients with optimal care. The program’s aim is to promote professional development, lifelong learning and quality assurance for the public and medical community. However, physicians are not happy with the current structure of the program, claiming it to be time-consuming, expensive and ineffective for their practice. The lack of concrete evidence confirming the efficacy of MOC in improving knowledge and clinical outcomes causes many to question how this system can be improved to better serve practitioners and the public. In this commentary, we provide an overview of the current MOC situation for U.S. specialists and highlight the importance of increasing research to inform evidence-based changes that can be applied to clinical situations.

Patients with ST-segment elevation myocardial infarction (STEMI) frequently present with multivessel coronary artery disease (CAD) during primary percutaneous coronary intervention, and the optimal timing of complete revascularization (CR) in these cases remains uncertain. This study aims to assess major adverse cardiovascular events (MACEs) and procedural complications in patients with STEMI with multivessel CAD who underwent immediate (index procedure) versus staged CR. We conducted a systematic review and meta-analysis of randomized controlled trials comparing immediate to staged CR in STEMI and multivessel CAD. Trials were identified by way of a systematic search of MEDLINE, Embase, and Cochrane Libraries from database inception to March 6, 2024. The data were analyzed using the RevMan software. A total of 5 randomized controlled trials (n = 1,415) were included in our study, which showed no significant differences in MACEs (13.3% vs 9.8%, relative risk [RR] 1.07, 95% confidence interval [CI] 0.62 to 1.83), all-cause mortality (3% vs 4.55%, RR 0.70, 95% CI 0.41 to 1.21), or myocardial infarction (4.5% vs 2.6%, RR 1.43, 95% CI 0.58 to 3.55) at a weighted mean follow-up duration of 16 months. However, the staged group had a higher rate of unplanned revascularization (8.6% vs 4.4%, RR 1.92, 95% CI 1.21 to 3.04). In conclusion, in patients with STEMI with multivessel CAD, at a mean follow-up of approximately 1.3 years, there is no significant difference in immediate versus staged revascularization (SR) for MACEs; however, SR was associated with a significantly higher incidence of unplanned ischemia-driven revascularization. SR within the index hospitalization may be as effective as immediate CR; further trials are needed to confirm this. We conducted a meta-analysis of 5 randomized controlled trials comparing immediate to staged complete revascularization in patients with ST-segment elevation myocardial infarction with multivessel coronary artery disease. There was no significant difference in major adverse cardiovascular events, all-cause mortality, and myocardial infarction rates between immediate and staged complete revascularization. However, staged revascularization was associated with a higher incidence of unplanned ischemia-driven revascularization. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/)

The current evidence regarding the long-term efficacy of electronic cigarettes (e-cigarettes) for smoking cessation is unclear. The purpose of this study was to assess the efficacy, safety, and tolerability of nicotine and non-nicotine e-cigarettes for smoking cessation in the general population. We randomized 376 adults who smoked ≥10 cigarettes/day and were motivated to quit at 17 Canadian sites to 12 weeks of nicotine (15 mg/mL) e-cigarettes (n = 128), non-nicotine e-cigarettes (n = 127), or no e-cigarettes (n = 121). All groups received individual counseling. The primary endpoint was point prevalence abstinence (7-day recall, biochemically validated using expired carbon monoxide) at 12 weeks. The 52-week follow-up results are reported here. Participants (mean age 52 ± 13 years; 47% female) smoked a mean of 21 ± 11 cigarettes/day at baseline. Compared to individual counseling alone, participants randomized to nicotine e-cigarettes plus counseling had higher rates of point prevalence (23.6% vs 9.9%; difference: 13.7%; 95% CI: 4.6%-22.8%) and continuous abstinence (3.1% vs 0.0%; difference: 3.1%; 95% CI: 0.1%-6.2%) and greater reductions in the number of cigarettes smoked (-9.5 ± 10.5 vs -5.6 ± 9.5; difference: -3.9; 95% CI: -6.5 to -1.4) at 52 weeks. Benefits were also observed among participants randomized to non-nicotine e-cigarettes plus counseling vs counseling alone. No differences in abstinence or reduction were found between nicotine and non-nicotine e-cigarettes. Compared to individual counseling alone, short-term use of standardized nicotine and non-nicotine e-cigarettes plus counseling is efficacious at increasing smoking abstinence at 52 weeks.

BACKGROUND:Recent randomized controlled trials (RCTs) have investigated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual or triple co-agonists for weight loss among adults with overweight or obesity and without diabetes. PURPOSE:To assess the efficacy and safety of GLP-1 RAs and co-agonists for the treatment of obesity among adults without diabetes. DATA SOURCES:MEDLINE, Embase, and Cochrane CENTRAL from inception to 4 October 2024. STUDY SELECTION:Placebo-controlled RCTs in otherwise healthy participants with overweight or obesity. DATA EXTRACTION:The primary outcome was change in relative or absolute body weight from baseline to maximum on-treatment follow-up. Safety outcomes included death, serious adverse events (SAEs), any adverse events (AEs), and gastrointestinal AEs. DATA SYNTHESIS:A total of 26 RCTs comprising 15 491 participants (72% female; mean body mass index, 30 to 41 kg/m2; mean age, 34 to 57 years) and 12 agents (3 commercially available agents [liraglutide, semaglutide, and tirzepatide] and 9 premarket agents for long-term weight management) were included. Treatment ranged from 16 to 104 weeks (median, 43 weeks). Compared with placebo, tirzepatide (15 mg once weekly) resulted in weight loss of up to 17.8% (95% CI, 16.3% to 19.3%) after 72 weeks of therapy; semaglutide (2.4 mg once weekly), up to 13.9% (CI, 11.0% to 16.7%) after 68 weeks; and liraglutide (3.0 mg once daily), up to 5.8% (CI, 3.6% to 8.0%) after 26 weeks. Retatrutide (12 mg once weekly) produced greater weight loss of up to 22.1% (CI, 19.3% to 24.9%) after 48 weeks; other novel single and combination GLP-1 agents were also efficacious to varying degrees. Although AEs were frequent (GLP-1 RA vs. placebo: 80% to 97% vs. 63% to 100%), the majority were gastrointestinal-related (47% to 84% vs. 13% to 63%, respectively), most commonly nausea, vomiting, diarrhea, and constipation. AEs requiring treatment discontinuation (0% to 26% vs. 0% to 9%, respectively) and SAEs (0% to 10% vs. 0% to 12%, respectively) were rare. LIMITATIONS:No head-to-head RCTs were available. Heterogeneity prevented meta-analysis. CONCLUSION:GLP-1 RAs and co-agonists are efficacious for weight loss, with reported safety concerns predominantly gastrointestinal in nature, when used among adults with overweight or obesity and without diabetes. PRIMARY FUNDING SOURCE:None. (PROSPERO: CRD42024505558).

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have become central in managing obesity and type 2 diabetes, primarily through appetite suppression and metabolic regulation. This review explores the mechanisms underlying GLP-1 RA-induced weight loss, focusing on central and peripheral pathways. Centrally, GLP-1 RAs modulate brain regions controlling appetite, influencing neurotransmitter and peptide release to regulate hunger and energy expenditure. Peripherally, GLP-1 RAs improve glycemic control by enhancing insulin secretion, reducing glucagon release, delaying gastric emptying, and regulating gut hormones. They also reduce triglycerides and low-density lipoprotein cholesterol, mitigate adipose tissue inflammation, and minimize ectopic fat deposition, promoting overall metabolic health. Emerging dual and triple co-agonists, targeting GLP-1 alongside glucose-dependent insulinotropic polypeptide, and glucagon pathways, may enhance weight loss and metabolic flexibility. Understanding these mechanisms is crucial as the therapeutic landscape evolves, offering clinicians and researchers insights to optimize the efficacy of current and future obesity treatments.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed obesity management, offering substantial weight loss and metabolic benefits. This review examines their expanding role, evaluating efficacy compared to alternative treatments, emerging indications, ongoing challenges, and future directions. Beyond obesity and type 2 diabetes, the therapeutic potential of GLP-1 RAs extends to a range of conditions such as cardiovascular disease, liver disease, neurodegenerative disease, and substance abuse disorders. While early concerns regarding pancreatic and thyroid cancer have been largely attenuated by recent evidence, issues such as gallbladder and biliary disorders, psychiatric safety, and perioperative aspiration risk require ongoing investigation. Additionally, observations of weight regain after treatment discontinuation and reductions in lean mass highlight the need for long-term, individualized strategies to sustain clinical benefits. The high cost and limited access to these medications raise critical policy and equity challenges. Future research must address these gaps, focusing on long-term safety, optimizing combination approaches, and evaluating the broader clinical and economic implications of widespread GLP-1 RA use. Funding:K.B.F. is supported by a William Dawson Scholar award from McGill University. T.M.P. is a Fond de Recherche du Québec-Santé (FRQS) research scholar. M.J.E. holds a James McGill Professor award from McGill University. The funding sources had no involvement in the conduct of this study, interpretation of results, or the preparation of this manuscript for publication.

BACKGROUND The current evidence regarding the long-term efficacy of electronic cigarettes (e-cigarettes) for smoking cessation is unclear. OBJECTIVES The purpose of this study was to assess the efficacy, safety, and tolerability of nicotine and non-nicotine e-cigarettes for smoking cessation in the general population. METHODS We randomized 376 adults who smoked >= 10 cigarettes/day and were motivated to quit at 17 Canadian sites to 12 weeks of nicotine (15 mg/mL) e-cigarettes (n = 128), non-nicotine e-cigarettes (n = 127), or no e-cigarettes (n = 121). All groups received individual counseling. The primary endpoint was point prevalence abstinence (7-day recall, biochemically validated using expired carbon monoxide) at 12 weeks. The 52-week follow-up results are reported here. RESULTS Participants (mean age 52 f 13 years; 47% female) smoked a mean of 21 f 11 cigarettes/day at baseline. Compared to individual counseling alone, participants randomized to nicotine e-cigarettes plus counseling had higher rates of point prevalence (23.6% vs 9.9%; difference: 13.7%; 95% CI: 4.6%-22.8%) and continuous abstinence (3.1% vs 0.0%; difference: 3.1%; 95% CI: 0.1%-6.2%) and greater reductions in the number of cigarettes smoked (-9.5 f 10.5 vs-5.6 f 9.5; difference:-3.9; 95% CI:-6.5 to-1.4) at 52 weeks. Benefits were also observed among participants randomized to non-nicotine e-cigarettes plus counseling vs counseling alone. No differences in abstinence or reduction were found between nicotine and non-nicotine e-cigarettes. CONCLUSIONS Compared to individual counseling alone, short-term use of standardized nicotine and non-nicotine e-cigarettes plus counseling is efficacious at increasing smoking abstinence at 52 weeks. (JACC Adv. 2025;4:101833) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction Millions of persons with chronic pain across North America and Europe use opioids. While the immunosuppressive properties of opioids are associated with risks of infections, these outcomes could be mitigated through careful patient selection and monitoring practices when appropriate. It is important to recognise that some patients do benefit from a carefully tailored opioid therapy. Enough primary studies have been published to date regarding the role of opioids in potential immunosuppression presenting as an increased rate of infection acquisition, infectious complications and mortality. There is thus a critical need for a consensus in this area.Methods and analysis The methodology is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies and the Cochrane Handbook for Systematic Reviews of Interventions. We plan to systematically search Ovid MEDLINE, CINAHL, PsycINFO, EMB Review, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Google Scholar databases from their inception date to December 2023. Full-text primary studies that report measurable outcomes in adults with chronic pain, all routes of opioid use, all types of infections and all settings will be included. We will identify a scope of reported infections and the evidence on the association of opioid use (including specific opioid, dosage, formulation and duration of use) with the risk of negative infectious outcomes. Opioid use-associated outcomes, comparing opioid use with another opioid or a non-opioid medication, will be reported. The meta-analysis will incorporate individual risk factors. If data are insufficient, the results will be synthesised narratively. Publication bias and confounding evaluation will be performed. The Grading of Recommendations Assessment, Development and Evaluation framework will be used.Ethics and dissemination Approval for the use of published data is not required. The results will be published, presented at conferences and discussed in deliberative dialogue groups.PROSPERO registration number CRD42023402812.

Despite the availability of a wide range of antihypertensive agents, a significant fi cant proportion of individuals with resistant hypertension (RHTN) struggle to achieve blood pressure (BP) control. Obesity ranks among the most significant fi cant modifiable fi able risk factors for RHTN, with 56-91% - 91% of patients with RHTN classified fi ed as overweight or obese. Glucagon-like peptide-1 receptor agonist (GLP-1 RAs) are a class of anti-obesity medications that have recently demonstrated efficacy fi cacy in reducing BP and improving cardiovascular (CV) outcomes in individuals with overweight or obesity. Among the available GLP-1-based therapies, liraglutide, semaglutide, and tirzepatide have been approved for chronic weight management in this population. Tirzepatide, a dual GLP-1 and glucose- dependent insulinotropic polypeptide receptor agonist, has the greatest effect on weight loss and BP reduction compared to GLP-1 RAs alone. To our knowledge, no trials have directly evaluated the effect of GLP-1 RAs or dual GLP-1/GIP receptor agonists on RHTN management. In this review article, we propose that targeting weight loss through GLP-1-based therapies should be explored as a treatment option for individuals with RHTN who are overweight or obese. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated that semaglutide, a GLP-1 receptor agonist, results in clinically important weight loss among individuals with type 2 diabetes. However, its effect on sustained weight loss among those without diabetes is unclear. Objective: To examine the long-term efficacy and safety of once-weekly semaglutide use for weight loss among individuals with obesity or overweight but without diabetes. Methods: We systematically searched MEDLINE, Embase, and the Cochrane Libraries to identify RCTs that randomized participants with obesity or overweight but without diabetes to a once-weekly 2.4 mg subcutaneous dose of semaglutide versus placebo. Inclusion was restricted to RCTs that reported change in body weight at a follow-up duration of ≥ 68 weeks. The primary outcome was relative change in body weight from baseline to 68 weeks. Random-effects models with inverse variance weighting estimated weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). Results: Three RCTs (n=2,783, 6.0% overweight [BMI 27 to 29.9 kg/m 2 ] and 94.0% obese [BMI ≥30 kg/m 2 ]) were included. Compared to placebo, once-weekly semaglutide was associated with decreased relative (WMD: -12.0%; 95% CI -13.9%, -10.2%; Table 1) and absolute body weight (WMD: -12.2; 95% CI -13.8, -10.6 kg) at 68 weeks. A total of 86.5% of participants randomized to semaglutide achieved ≥5% weight loss compared to 34.8% with placebo (RR: 2.41; 95% CI 1.26, 4.64). The incidence of gastrointestinal adverse events was higher with semaglutide (RR: 1.45; 95% CI 1.14, 1.84); however, the majority of these events were transient, mild-to-moderate in severity, and did not require treatment discontinuation. A low incidence of serious adverse events was reported (9.5%). CONCLUSIONS: Among individuals with obesity or overweight but without diabetes, semaglutide is efficacious for sustained weight loss.

Medical school candidates must have both the cognitive and professional competencies required to become good physicians. In this commentary, we outline the evidence and outcomes associated with the implementation of these selection methodologies and evaluate their ability to assess non-cognitive skills.

Obesity is a chronic disease whose prevalence has increased to epidemic proportions in North America and across the world. Leading organisations in healthcare have compiled guidelines to help primary care practitioners screen, manage and treat patients with overweight and obesity. This review is the final part of our three-part series conducting an overview of the current clinical guidelines for obesity management. In this review, we provide an overview of the types of bariatric surgery, eligible populations, weight loss outcomes and future directions of surgical intervention for weight loss. Obesity is an important health issue that can lead to significant impacts on the heath. In severe cases, bariatric surgery is an appropriate intervention to help patients lose weight. This weight loss is associated with improved quality of life and comorbidity remission.

Aims:Cardiogenic shock (CS) develops in up to 10% of patients with acute myocardial infarction (AMI) and carries a 50% risk of mortality. Despite the paucity of evidence regarding its benefits, venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in clinical practice in patients with AMI in CS (AMI-CS). This review aims to provide an in-depth description of the four available randomized controlled trials to date designed to evaluate the benefit of VA-ECMO in patients with AMI-CS. Methods and results:The literature search was conducted on PubMed, Google Scholar, and clinicaltrials.gov to identify the four relevant randomized control trials from years of inception to October 2023. Despite differences in patient selection, nuances in trial conduction, and variability in trial endpoints, all four trials (ECLS-SHOCK I, ECMO-CS, EUROSHOCK, and ECLS-SHOCK) failed to demonstrate a mortality benefit with the use of VA-ECMO in AMI-CS, with high rates of device-related complications. However, the outcome of these trials is nuanced by the limitations of each study that include small sample sizes, challenging patient selection, and high cross-over rates to the intervention group, and lack of use of left ventricular unloading strategies. Conclusion:The presented literature of VA-ECMO in CS does not support its routine use in clinical practice. We have yet to identify which subset of patients would benefit most from this intervention. This review emphasizes the need for designing adequately powered trials to properly assess the role of VA-ECMO in AMI-CS, in order to build evidence for best practices.

Background To combat the opioid crisis, interventions targeting the opioid prescribing behaviour of physicians involved in the management of patients with chronic non-cancer pain (CNCP) have been introduced in clinical settings. An integrative synthesis of systematic review evidence is required to better understand the effects of these interventions. Our objective was to synthesize the systematic review evidence on the effect of interventions targeting the behaviours of physician opioid prescribers for CNCP among adults on patient and population health and prescriber behaviour. Methods We searched MEDLINE, Embase, and PsycInfo via Ovid; the Cochrane Database of Systematic Reviews; and Epistemonikos. We included systematic reviews that evaluate any type of intervention aimed at impacting opioid prescriber behaviour for adult CNCP in an outpatient setting. Results We identified three full texts for our review that contained 68 unique primary studies. The main interventions we evaluated were structured prescriber education (one review) and prescription drug monitoring programmes (PDMPs) (two reviews). Due to the paucity of data available, we could not determine with certainty that education interventions improved outcomes in deprescribing. There is some evidence that PDMPs decrease the number of adverse opioid-related events, increase communication among healthcare workers and patients, modify healthcare practitioners’ approach towards their opioid prescribed patients, and offer more chances for education and counselling. Conclusions Our overview explores the possibility of PDMPs as an opioid deprescribing intervention and highlights the need for more high-quality primary research on this topic.

Background: Essential hypertension, a prevalent cardiovascular condition, poses a significant health burden worldwide. Based on the latest American clinical guidelines, half of adults in the United States have hypertension. Of these, only about a half are treated and about a quarter are adequately controlled for hypertension. Given its impact on morbidity and mortality, ensuring effective management of high blood pressure is crucial to reduce associated risks and improve patient outcomes.Objective: This review aims to provide a comprehensive and up-to-date summary of the latest cardiology guidelines and evidence-based research on essential hypertension, with a focus on guiding outpatient clinical practice.Methods: The review evaluates both non-pharmacological approaches and pharmacological interventions to offer clinicians practical insights. Notably, it emphasizes the importance of individualized treatment plans tailored to patients' specific risk profiles and comorbidities.Results: By consolidating the latest advancements in hypertension management, this review provides clinicians with an up-to-date reference, offering a nuanced understanding of treatment goals and strategies.Conclusion: Through the incorporation of evidence-based recommendations, healthcare practitioners can optimize patient care, mitigate potential complications, and improve overall outcomes in essential hypertension.