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Recent studies have demonstrated that inhibiting various steps of TMAO production can reduce TMAO levels and treat AS (9, 8588) (Figure 4)

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The recent phase 2 trial of tirzepatide in patients with MASH provides support for the therapeutic potential of GIPpathway modulation in cardiometabolic disease and demonstrates how GIP signaling, when cotargeted with GLP-1RA, may contribute to weight loss, improved metabolic outcomes, and possibly cardiovascular protection ( 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