The role of insulin resistance and insulin-sensitizers in NASH management: tips for the practicing clinician

Prof Kenneth Cusi, USA, discusses the role of insulin sensitizers in NASH, and particularly how lifestyle interventions including weight loss can, in this context, be beneficial together with a pharmacological approach.
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The role of insulin sensitizer in NASH (non-alcoholic steatohepatitis) is increasingly being studied and understood but it is quite complex. So for the practicing clinician, it’s important to understand that a low annual model suggests insulin resistance as activating many pathways, this has not been that clear cut in humans. On the other hand, we do know that you will not get NASH if you don’t have insulin resistance. In other words, while insulin resistance is one of the mechanisms, reversing it will clearly have metabolic and liver-specific benefits. 

Other management strategies for NASH

So the key thing here is how you can do that in your office. Number one is weight loss, by any means. Either lifestyle, lifestyle with medication or surgery; just do it. Secondly, exercises can help even without changes in weight, but for most of our patients, we’re going to need to add medication. This is firstly because weight loss is difficult, difficult to maintain and the benefits of fibrosis are variable. Instead, some medications that attack insulin resistance can have a specific effect. 

Pioglitazone as a medication to manage NASH

For example, our best studied drug for NASH is pioglitazone, which is a generic and very cheap medication. That can show clear benefits in patients in NASH with both weight and without diabetes and the liver guidelines want you to use them. How do you use it? You start low and then move up but the key concept is that it is not only a mechanism that will be because of the benefits on the liver and outside of the liver, many pharmaceutical companies are developing compounds that will try to mimic the good of pioglitazone while limiting the weight gain. Weight gain is preventable if we do a multidisciplinary approach in which we ask the patients to change their lifestyle because what you’re doing is changing the biology of fat from that of an obese sick fat to an obese individual with fat that functions  like that of a lean person. So where we stand today is to start low doses of pioglitazone (15mg or 30mg) and let’s wait for the results of the new compounds coming out in the pipeline.

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Prof. Kenneth Cusi

Prof. Kenneth Cusi

Dr. Cusi is a Professor of Medicine and Chief of the Division of Endocrinology, Diabetes and Metabolism at The University of Florida at Gainesville (2011-present). He is also a faculty and researcher at the Endocrinology, Diabetes and Metabolism Division at the Veterans Administration Medical Center at...

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