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Conclusion Leptin resistance significantly limits the therapeutic efficacy of leptin in obesity, arising from multiple mechanisms, including hyperleptinemia, impaired JAK2STAT3 signaling, defective autophagy, ER stress, inflammation, reduced leptin receptor expression, signaling pathway dysfunction, increased mTOR activity, and peripheral resistance

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These numbers exceeded the Phase 2 results, partly because the trial ran longer (68 weeks versus 48 weeks) and partly because the dose escalation schedule was refined

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Iron levels were substantially higher in DS from Suppliers 1, 2, and 4 (range: 1.66.5 g/g) than in originator liraglutide (0.9 g/g), as were copper and zinc levels (range: 0.934.5 vs

This may be related to more awareness, increased access to echo, or a change in the presentation of VSR due to earlier reperfusion strategies