From the Guidelines
DPP-4 inhibitors should be used with caution in patients with liver disease, particularly in those with decompensated cirrhosis, due to the lack of robust evidence on their safety and efficacy in this population. The use of DPP-4 inhibitors in liver disease is not yet FDA-approved, and their effects on liver histological end points are unknown 1. However, some studies suggest that DPP-4 inhibitors may have beneficial effects in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) by reducing liver inflammation and fat accumulation 1. Common DPP-4 inhibitors include sitagliptin, linagliptin, saxagliptin, and alogliptin, which work by preventing the breakdown of incretin hormones and improving glucose metabolism.
In patients with type 2 diabetes and NAFLD, DPP-4 inhibitors may be considered as part of a comprehensive management plan, but their use should be individualized and monitored closely. It is essential to note that metformin, a commonly used medication for type 2 diabetes, is contraindicated in patients with decompensated cirrhosis due to the risk of lactic acidosis 1. In contrast, DPP-4 inhibitors, such as linagliptin, do not require dosage adjustments in patients with liver or renal insufficiency 1.
Key considerations for the use of DPP-4 inhibitors in liver disease include:
- Potential benefits in reducing liver inflammation and fat accumulation
- Lack of robust evidence on safety and efficacy in patients with decompensated cirrhosis
- Individualized treatment plans and close monitoring
- Consideration of alternative medications, such as GLP-1 receptor agonists, which have shown promise in improving liver histology 1. Overall, the decision to use DPP-4 inhibitors in patients with liver disease should be made on a case-by-case basis, taking into account the individual patient's needs and the potential risks and benefits of treatment.
From the Research
DDP4 Inhibitors in Liver Disease
- DDP4 inhibitors, such as sitagliptin, have been studied for their efficacy and safety in treating diabetes mellitus complicated by chronic liver injury 2.
- The use of DDP4 inhibitors in patients with liver cirrhosis has shown mixed results, with some studies suggesting a reduction in HbA1c levels without deterioration of liver enzymes 2, while others have found an increased risk of decompensated cirrhosis and hepatic failure 3.
- In animal models, DDP4 inhibitors have been shown to reduce portal hypertension in cirrhotic rats by normalizing arterial hypocontractility 4.
Effects on Non-Alcoholic Fatty Liver Disease (NAFLD)
- A systematic review and meta-analysis found that sitagliptin improved serum gamma-glutamyl transpeptidase (GGT) levels in patients with NAFLD, but had no significant effect on liver transaminase or liver fat content 5.
- Another study found that sitagliptin alleviated liver inflammation in diabetic mice by acting as a ROS scavenger and inhibiting the NFκB pathway 6.
Safety and Efficacy
- Sitagliptin has been shown to be safe and well-tolerated in patients with NAFLD, with only minor gastrointestinal side effects reported 5.
- However, the use of DDP4 inhibitors in patients with liver cirrhosis requires careful consideration, as some studies have suggested an increased risk of adverse outcomes 3.