Cardioprotective Outcomes of Next-Generation Dual Amylin and Calcitonin Receptor Agonists in Patients with Ischemic Cardiomyopathy and Advanced Obesity

International Journal of Cardiology | Vol. 17, No. 3, March 2026 | pp. 173–181

DOI: 10.46882/2026/IJC/001843

Original Research Article

Cardioprotective Outcomes of Next-Generation Dual Amylin and Calcitonin Receptor Agonists in Patients with Ischemic Cardiomyopathy and Advanced Obesity

Sarah Jenkins¹, David Cooper²

¹ Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, USA
² Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, USA

Abstract:
Obesity profoundly accelerates adverse ventricular remodeling in patients with established ischemic cardiomyopathy (ICM). Dual amylin and calcitonin receptor agonists (DACRAs) represent a novel therapeutic class with potent metabolic and anti-inflammatory properties. This double-blind, randomized, placebo-controlled trial investigated the long-term cardioprotective and structural effects of the novel DACRA compound, Cagrilintide-Z, in obese patients with chronic ICM. A total of 280 participants with a body mass index greater than or equal to 35 kg/m² and a baseline left ventricular ejection fraction (LVEF) of 30-40% were randomized to weekly subcutaneous Cagrilintide-Z (4.5 mg) or a matching placebo for 48 weeks. The primary outcome was change in LVEF assessed by cardiovascular magnetic resonance. After 48 weeks, the Cagrilintide-Z arm experienced a mean weight loss of 15.4% (± 2.1%) compared to 1.8% (± 0.5%) in the placebo arm (p < 0.001). Crucially, the treatment group exhibited a significant increase in LVEF (+4.8% ± 0.9% vs. +1.1% ± 0.4%, p = 0.002) and a simultaneous decrease in left ventricular end-diastolic volume index (-12.4 mL/m² vs. -2.1 mL/m², p < 0.01). Circulating high-sensitivity C-reactive protein levels decreased by 44% in the DACRA cohort (p < 0.001). In conclusion, weekly administration of Cagrilintide-Z safely promotes substantial weight loss and delivers profound, independent cardioprotective benefits by reversing adverse structural remodeling and suppressing systemic inflammation in obese individuals with ischemic cardiomyopathy.

Keywords: Ischemic cardiomyopathy, Obesity, Dual amylin and calcitonin receptor agonists, Ventricular remodeling, Cardiovascular magnetic resonance, Inflammation

Received: December 19, 2025; Revised: January 22, 2026; Accepted: February 10, 2026; Published: March 11, 2026

Citation: Jenkins S, Cooper D. Cardioprotective Outcomes of Next-Generation Dual Amylin and Calcitonin Receptor Agonists in Patients with Ischemic Cardiomyopathy and Advanced Obesity. International Journal of Cardiology, 2026; 17(3): 173–181. DOI: 10.46882/2026/IJC/001843

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