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When evaluated in a meta-analysis, there was an overall improvement in the histopathologic components of NASH (ballooning RR 1.62 and OR 2.11, steatosis RR 2.03 and OR 3.39, and inflammation RR 1.71 and OR 2.58), with improvements in fibrosis (RR 1.38 and OR 1.68).[29], [30], [31] The major downside to the use of pioglitazone is patient and physician acceptance, given its propensity to induce weight gain (average 4.4 kg).25 It should not be used in patients with clinically evident heart failure and may promote post-menopausal bone loss.[32], [33] Given the increasing disease burden and limited efficacy and safety of current treatment options, the development of additional pharmacologic therapies to treat NASH is critical

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Subcutaneous and intraperitoneal routes give shorter circulating windows, with the compound clearing primarily through proteolytic degradation outside the GI tract rather than through renal or hepatic elimination as a single molecule

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CCS 22 (1), 114