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Individuals with active malignancy, uncontrolled serious illness, pregnancy, breastfeeding, or complex immune or coagulation disorders are commonly considered poor candidates and require alternative strategies

The TRIUMPH-4 Phase 3 trial in obesity with knee osteoarthritis (Bays et al., NEJM 2025) reported 28.7% mean weight loss at 68 weeks at the 12 mg dose, plus a 75.8% reduction in WOMAC knee pain scores

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The latter causes accumulation of AICAR, a well-defined AMPK activator