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In addition, activation of Smad2/3 by NLRP3 phosphorylates vascular endothelial cells and transforms them into myofibroblasts, thereby increasing the production of -SMA and MMP9 [199]

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Phase 2 clinical trial data published in the New England Journal of Medicine showed up to 24.2% body weight reduction at 48 weeks the highest ever reported in any obesity clinical trial

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The study found patients treated with combination sirolimus and metformin had significantly longer survival and disease-free survival than other groups.23 More randomized clinical controlled trial data is needed as well as studies that analyze adverse events between single and combination agent treatment groups

doi: 10.1111/j.1365-2125.2012.04272.x