Efficacy and Safety of Non-surgical Bariatric Therapies for Non-alcoholic Steatohepatitis and Metabolic Syndrome: A Comparative Meta-Analysis

Abstract

Introduction: While non-alcoholic steatohepatitis (NASH) and metabolic syndrome (METS) have a multidimensional etiology, weight loss remains at the forefront of current therapies. Recent data suggests that a greater than 10% weight loss is associated with a significant decrease in hepatic steatosis, necroinflammation, and fibrosis. Several non-surgical weight loss interventions have been investigated, but it is unclear whether one is better than the others. The aim of this study was to perform a systematic review and structured meta-analysis to evaluate the comparative effectiveness and safety of non-surgical weight loss therapies. Methods: A comprehensive search of PubMed and EMBASE was performed through November 2015 to identify studies in adults with NASH or METS and minimum one-month follow-up involving nonsurgical bariatric therapies. Interventions included lifestyle modification, Optifast weight loss program, FDA approved weight loss medications (orlistat, lorcaserin, phentermine plus topiramate, naltrexone plus bupropion, and liraglutide), and the OrberaTM intragastric balloon [IGB]). Primary outcome measures were: percent weight loss, early treatment discontinuation, and serious adverse events. A proportion meta-analysis was performed. The individual study proportion was first transformed into a quantity using the Freeman-Tukey variant of the arcsine square root transformed proportion. The pooled proportion was then calculated as the back transform of the weighted mean of the transformed proportion, using inverse arcsine variance weights for the fixed effects model and DerSimonian-Laird weights for the random effects model. Publication bias was evaluated by visual inspection of funnel plots. Results: We analyzed data from 193 studies that met inclusion criteria: 41 studies on lifestyle modification (n=7,612), 7 studies on the Optifast program (n=932), 89 studies on FDA approved weight loss pharmacotherapy (n=31,752), and 56 studies on IGB therapy (n=6,160). Table 1 summarizes the outcomes of all non-surgical weight loss therapies.Table 1: Characteristics and outcomes of all non-surgical weight loss therapies.Conclusion: Only Optifast weight loss program, phentermine plus topiramate, and IGB therapy showed a meaningful ≥10% weight loss associated with potential for NASH fibrosis reversal. IGB therapy was the most effective non-surgical weight loss treatment and is relatively safe. Expanded use of this treatment modality is indicated to combat the rising epidemic of NASH and METS.