GLP-1 receptor agonists in the treatment of diabetic non–alcoholic steatohepatitis patients

ABSTRACT

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease affecting almost 30% of the world population. Approximately 25% of people with NAFLD develop nonalcoholic steatohepatitis (NASH), the fulminant version of the disease. Diabetes mellitus is present in 22.5% of people with NAFLD and 44.60% of individuals with NASH. This review was undertaken to examine the current contribution of glucagon-like peptide 1 (GLP-1) receptor agonists to the pharmacotherapy of diabetic nonalcoholic steatohepatitis.

Areas covered

The author analyzed the current status of GLP-1 receptor agonists for pharmacotherapy of diabetic NASH. Research data and literature reports were taken from the database and or websites of Diabetes UK, American Diabetes Association, ClinicalTrials.gov, PubMed, and Scopus. The keywords utilized included type 2 diabetes, GLP-1, NASH, NAFLD, and clinical trials.

Expert opinion

Since diabetic NASH is associated with obesity, diabetes mellitus, oxidative stress and inflammation, drugs capable of mitigating all of these conditions simultaneously, are most ideal for the treatment of diabetic NASH. These drugs include (in order of relevance), GLP-1 receptor agonists, GLP-1 and GIP dual receptor agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and pioglitazone. The future, FDA-approved drug for diabetic NASH treatment will likely be GLP-1 agonist, which could be used as monotherapy or in combination with other drugs.

KEYWORDS:

• GLP-1 receptor agonists
• GLP-1 and GIP dual receptor agonists
• diabetes mellitus
• nonalcoholic steatohepatitis
• pharmacotherapy
• obesity
• insulin resistance
• dyslipidemia
• PNPLA3 gene

Article highlights

• More than 30% of people worldwide has nonalcoholic fatty liver disease (NAFLD) a, precursor of nonalcoholic steatohepatitis (NASH).

• 20% of people with NAFLD will develop NASH.

• NASH can be induced by genetic, environmental and metabolic factors.

• Prevalence of NASH will increase by 15-56% from the year 2016 through 2030.

• Diabetes mellitus, obesity and dyslipidemia are the most important risk factors for NASH.

• The US spends $103 billion annually to treat NAFLD whereas, the major EU industrialized countries (Germany, France, Italy, UK) disburse €35 billion per annum.

• GLP-1 receptor agonists and GLP-1 and GIP dual receptor agonists are the most ideal drugs to simultaneously reduce body weight, treat diabetes mellitus, and reduce the oxidative stress and inflammation associated with diabetic NASH.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.