1.) Why This Paper Matters Type 2 diabetes is ubiquitous, and cardiovascular disease is the leading cause of morbidity and mortality in diabetic patients. GLP‑1 receptor agonists have consistently shown improvements in reducing cardiovascular risk, but oral formulations were unavailable until recently. The SOUL trial examines whether oral semaglutide can reduce major adverse cardiovascular events (MACE) in high-risk adults. Key learning points for members: - How to identify what outcomes are clinically relevant - How to interpret absolute vs relative risk - How to approach papers yourself in a structured way 2.) Study Design & Population - Design: Phase III, randomized, double-blind, placebo-controlled trial - Participants: ~9,650 adults with type 2 diabetes and established cardiovascular disease, chronic kidney disease, or both - Intervention: Oral semaglutide (tablet) vs placebo (in addition to standard of care) - Follow-up: Median ~4 years - Inclusion/Exclusion: Adults age 50 or greater, with HbA1c 6.5-10%, high CV risk; excluded severe GI disease or recent major CV events 3.) Methods & Statistics - Primary outcome: Composite MACE (CV death, nonfatal MI, nonfatal stroke) - Analysis: Intention-to-treat; hazard ratios (HR) with 95% confidence intervals - Power: Designed to detect ~15% relative risk reduction - Other outcomes: HbA1c, weight, safety/adverse events - Why this matters: Learn how hazard ratios, confidence intervals, and absolute vs relative risk inform clinical interpretation 4.) Results - MACE: HR 0.86 (14% relative reduction) vs placebo - Absolute risk reduction: 1.8% over ~4 years - Weight & glycemic control: Significant reductions with semaglutide - Adverse events: Mostly mild/moderate GI events; serious events similar between groups - Subgroups: Benefits observed broadly, slightly attenuated in lower-risk populations 5.) Strengths & Limitations Strengths: - Large sample size - Double-blind, placebo-controlled - Definitive and observable cardiovascular outcomes - Long follow-up

Welcome - and thanks for joining. This is a clinician-focused journal club designed to help healthcare professionals stay current with new medical literature without drowning in papers or stats. The goal here is simple: Help you identify what's truly relevant in a paper, and give the the tools to read and interpret medical literature with confidence. What this community is - A weekly breakdown of clinically relevant medical literature - Clear explanations of study design, statistics, and real-world applicability - Guidance on how to approach papers yourself, so you can build independent skills for evaluating evidence - Active discussion where questions and different perspectives are encouraged - Focused on practice-changing (or practice-clarifying) studies What this community is NOT - Not medical advice - Not specialty-specific board prep or resource - Not a paper dump or academic exercise Focus should be on what actually matters for clinical decision-making. How to participate - Read one paper per week in the "Weekly Journal Club" channel - Follow the structured breakdown: why it matters, study design, results, statistical considerations, and clinical implications - Engage in discussion in the "Open Discussion" channel Time commitment: ~10-20 minutes/week to read +/- optional participation About this Pilot - This is a free pilot cohort while we refine the format and teaching approach. After the pilot, the community will transition to a paid membership, and early members will receive founding member pricing as a thank you for helping shape the group. DISCLAIMER: All content is for educational purposes only and does not constitute medical advice. I'm excited to help try to cut through the noise, read papers more effectively, and make better, evidence-informed decisions in practice. -Jerry