Combining SGLT2 Inhibitors and Pioglitazone May Reduce Risk of MASH in Type 2 Diabetes, Study Finds

The findings, published in Diabetes, Obesity and Metabolism, suggest that this combination therapy could offer an effective strategy for managing liver-related complications in individuals with type 2 diabetes who are at risk for developing MASH.

MASH, a condition that includes a spectrum of liver abnormalities, such as fatty liver and non-alcoholic steatohepatitis (NASH), is increasingly recognized as a significant comorbidity in patients with type 2 diabetes. Both conditions share common risk factors such as insulin resistance, obesity, and inflammation, which often make them challenging to manage concurrently. Given the rising global prevalence of type 2 diabetes, finding effective treatments for liver complications associated with this condition has become a priority in clinical research.

Both pioglitazone and glucagon-like peptide 1 receptor agonists (GLP1RAs) have improved MASH in randomized clinical trials. Meanwhile, preclinical studies have suggested the potential benefits of SGLT2i for managing MASH. In real-world clinical practice, patients with type 2 diabetes often need a combination of medications to effectively control blood sugar levels. In the study, Chi-Ho Lee, State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China, and colleagues explored the potential benefits of combining these therapies to reduce the risk of MASH in patients with type 2 diabetes.

For this purpose, the researchers measured longitudinal changes in the FibroScan-aspartate aminotransferase (FAST) score in 888 patients with type 2 diabetes. Pioglitazone, GLP1RA, and/or SGLT2i use were defined as continuous prescriptions for at least 180 days before the patients' last reassessment using FibroScan. Multivariable logistic regression analysis was performed to evaluate the associations between the use of these medications and changes in the FAST score.

The study revealed the following findings:

• Over a median follow-up of 3.9 years, an increasing number of medications (pioglitazone, GLP1RA, and/or SGLT2i) used was significantly associated with greater reductions in the FAST score.
• Dual combination therapy is independently linked to a higher likelihood of achieving a low FAST score at reassessment than using any single agent (odds ratio [OR] 2.84).
• Among different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together was associated with:
  • A higher likelihood of achieving a low FAST score at reassessment than not using any of the three agents (OR 6.51).
  • A higher likelihood of FAST score regression (OR 12.52).
• These associations remained significant after adjusting for changes in glycemic control and body weight during the study.

"The findings showed that combining SGLT2 inhibitors and pioglitazone may be an effective strategy for improving at-risk MASH in patients with type 2 diabetes," the researchers concluded.

Reference:

DOI: https://doi.org/10.1111/dom.16049