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These combined mechanisms underpin their efficacy for both weight reduction and cardiometabolic protection ( In recent years, the remarkable efficacy of tirzepatide, a dual GIP/GLP-1 receptor agonist, has emerged ( However, these benefits are accompanied by concerns about side effects, cost, long-term sustainability and, above all, the loss of lean mass, which may be mitigated by concurrent exercise ( Exercise and lifestyle interventions remain foundational for obesity and metabolic disease management, offering broad health benefits, but are often limited by adherence and modest long-term weight loss ( Recent randomized controlled trials and meta-analyses suggest that combining GLP-1RAs with exercise may yield additive or synergistic effects on weight loss and metabolic syndrome severity as well as on oxidative stress and inflammation

Raab EL, Vuguin PM, Stoffers DA, Simmons RA

NNMT is a cytosolic enzyme that methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor

, Giovino, G

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1,5 Dietary patterns that emphasize healthy fats like olive oil, avocados, nuts, and omega-3 fatty acids effectively maintain GLP-1 activity after meals longer than those heavy in saturated fats, thus supporting better insulin sensitivity and glucose control