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Pannexin-1 channel opening is critical for COVID-19 pathogenesis
RCT SUMMIT - Tirzepatide vs Placebo for Heart Failure with Preserved Ejection Fraction and Obesity, NEJM (2024) [PubMed abstract] The SUMMIT trial enrolled 731 patients with heart failure, an ejection fraction of at least 50%, and a BMI of 30 or more Main inclusion criteria Age 40 years NYHA class II-IV EF 50% BMI 30 KCCQ-CSS of 80 or lower Main exclusion criteria Cardiomyopathy Uncontrolled hypertension History of bariatric surgery HbA1c 9.5% Baseline characteristics Age - 65.3 years Female sex - 53.8% NYHA class: II - 72.5% | III or IV - 27.5% Average body weight - 227 lbs (103 kg) Average BMI - 38.3 Average EF - 60.8% History of CAD - 30% Median NT-proBNP level - 183 pg/ml Average GFR - 64.4 ml/min Average KCCQ-CSS score - 53.6 Heart failure exacerbation within 12 months - 46.9% Atrial fibrillation - 25.5% Type 2 diabetes - 48.2% Randomized treatment groups Group 1 (364 patients): Tirzepatide with a target dose of 15 mg once weekly Group 2 (367 patients): Placebo Tirzepatide was started at 2.5 mg once weekly and increased by 2.5 mg every 4 weeks as tolerated (1) Composite of adjudicated death from cardiovascular causes or a worsening heart-failure event
To maintain GSCs and proliferative cell fate, GLP-1/Notch activity must remain above a threshold for proliferation/differentiation decision
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