Pioglitazone for optimisation of clinical nutrition therapy in the critically ill patient: A Systematic Review

Background Skeletal muscle wasting is a major determinant of physical functional disability in critical illness survivors, and contributes to post-intensive care syndrome. As yet, no therapies exist to address this major public health issue. Intramuscular bioenergetic failure and inflammation are understood to be the underpinning mechanisms, and carbohydrate and lipid oxidation are impaired. This systematic review synthesises the evidence that peroxisome proliferator-activated receptor gamma agonists may be a therapeutic option to optimise clinical nutrition in critically ill patients. Method Systematic review and meta-analysis. Results Fourteen studies over 19 publications were included. Lean body mass was unaffected (n=174). Pioglitazone treatment resulted in periperal insulin sensitivity increasing 30-71% (Standardised mean change 0.97 (95%CI 0.36-1.58; n=213). Intramuscular Tumour Necrosis Factor Alpha concentrations decreased in treatement arms (n=29) as did circulating interlukin-6 and Tumour Necrosis Factor Alpha (n=53). Intramyocellular Lipid concentrations decreased by 34-40% with pioglitazone therapy (n=60). Treatment increased intramuscular markers of Oxidative Phosphorylation (n=55), mitochondrial biogenesis(PGC1α and PGC1β; n=26) and β-oxidation (n=29) Conclusions Pioglitazone therapy increases skeletal muscle insulin sensitivity, decreases intramyocellular lipid accumulation and systemic and intramuscular inflammation. Where lean body mass was measured, this was seen to increase. Pioglitazone may be an adjunctive therapy to optimise clinical nutrition in acutely unwell patients. Clinical relevancy statement Pioglitazone may optimise clinical nutrition therapy in critically ill patients by normalising carbohydrate and lipid metabolism.