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Abstract Tirzepatide, a dual agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown robust efficacy in treating diabetes and obesity, and in obese patients with heart failure with preserved ejection fraction (HFpEF), it reduced weight, lowered blood pressure, and improved outcomes

Protocol 2: significant weight loss (20-25% body weight) Goal: Substantial weight reduction for health improvement Tirzepatide approach: Full escalation to 10-15 mg Expect to reach target dose by week 17-21 Weight loss at 15 mg: approximately 22.5% at 72 weeks Plateau typically occurs around weeks 60-72 Retatrutide approach: Full escalation to 8-12 mg Expect to reach target dose by week 13-17 Weight loss at 12 mg: 24.2% at 48 weeks, 28.7% at 68 weeks No plateau observed in trial data at 48 or 68 weeks For significant weight loss goals, retatrutide reaches 20%+ body weight reduction faster and ultimately achieves a higher ceiling

Watanabe M, Cromwell HC, Tremblay L, Hollerman JR, Hikosaka K, Schultz W

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