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Liraglutide and Sitagliptin Useful for Nonalcoholic Fatty Liver Disease in T2DM

Aug 20, 2019
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Amber Satz, PharmD Candidate, LECOM School of Pharmacy

A recent study reveals Liraglutide and Sitagliptin reduce intrahepatic lipid in patients with nonalcoholic fatty liver disease in T2DM.

Nonalcoholic fatty liver disease (NAFLD) occurrence is growing to be a major public health problem as it is the most common cause of chronic liver disease. NAFLD is comprised of several contributing conditions of the liver, including the excessive deposition of fat within the liver, progressive inflammation, and fibrosis; this essentially results in nonalcoholic steatosis (NASH). Risk factors for NAFLD are closely linked to metabolic syndrome including metabolic syndrome itself, obesity, physical inactivity, a high-calorie diet comprised of excess saturated fats, refined carbohydrates, sugar-sweetened beverages, and high fructose intake, and obstructive sleep apnea. NAFLD often occurs in patients with type 2 diabetes. One report identified that T2DM was present in 23% of patients with NAFLD and 47% of patients with NASH.

Currently, treatment recommendations for NAFLD management are geared towards weight loss through improved diet and lifestyle; there are no approved pharmacological treatments for NAFLD. As the relationship between NAFLD and type 2 diabetes is so strong, there is a great interest in determining whether any diabetes pharmacological treatments exhibit benefit on NAFLD. Studies have determined that metformin does not have any effect on NAFLD and currently, no studies are available to display the efficacy of additional add-on diabetes therapy for the management of NAFLD. A randomized, double-blind, placebo-controlled trial conducted on patients with prediabetes and diabetes with NAFLD did not show any effect on liver fat from sitagliptin compared to placebo. Mixed results have been reported about the efficacy of Liraglutide for this indication: The Liraglutide Efficacy and Action in NASH (LEAN) study showed a significant resolution of NASH and reduction in fibrosis compared to placebo in patients with NASH, 9 with T2DM. On the other hand, two randomized studies exhibited no reduction of liver fat from liraglutide in patients with T2DM. Studies regarding basal insulins’ effect on liver fat show mixed results, as well.

A recent study was published that may show some promising efficacy from liraglutide and sitagliptin added to metformin. This was a 26-week, open-label, active-controlled, parallel-group, multicenter trial conducted at 10 centers in China. Patients aged 30-75 years old with T2DM (HbA1c 6.5%-10%) that have been treated with metformin monotherapy ≥1500 mg/day for at least three months and were diagnosed with NAFLD were included. 75 patients were randomized to receive either liraglutide 1.8 mg daily, sitagliptin 100 mg once daily or insulin glargine at bedtime, in addition to their concurrent metformin dose. 65 patients finished the study: in the liraglutide and sitagliptin groups, the primary efficacy endpoint, intrahepatic lipid (IHL) measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), significantly decreased from baseline (liraglutide 15.4%  5.6% to 12.5% 6.4%, p < 0.001; sitagliptin 15.5% 5.6% to 11.7% 5.0%, p = 0.001). No significant change was observed in the insulin glargine group. Multiple linear regression analysis revealed that change in weight was an independent determinant of change in MRI-PDFF in T2DM and NAFLD (p = 0.031) with adjustment for effects of antidiabetic agents, change in HbA1c, change in subcutaneous adipose tissue and change in visceral adipose tissue, whereas other measurements did not show association with change in MRI-PDFF. No treatment group displayed any change in hepatic fibrosis, but this could be due to the short treatment period.

In summary, this study provides evidence that both liraglutide and sitagliptin, in combination with metformin as a first-line add-on therapy for type 2 diabetes, can also improve intrahepatic lipid for patients with T2DM and NAFLD. Also, liraglutide, as previously determined in several diabetes studies, significantly reduced body weight whereas insulin glargine did not. As in the Lira-NAFLD Study, weight loss is highly correlated with the reduction of IHL. For patients with T2DM and NAFLD, liraglutide and sitagliptin are viable options for both glycemic control and reduction of IHL.

Practice Pearls:

  • While T2DM is highly correlated with obesity, it is also seen to be linked to non-alcoholic fatty liver disease which leads to poor outcomes including cirrhosis and liver cancer.
  • A recent study showed that diabetes medications liraglutide and sitagliptin, in combination with metformin, can improve intrahepatic lipid and therefore benefit NAFLD.
  • Liraglutide and sitagliptin may be good diabetes medications for patients with T2DM and NAFLD.

 

References: “Liraglutide and Sitagliptin Useful for Nonalcoholic Fatty Liver Disease in T2DM”

Yan, Jinhua, et al. “Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.” Hepatology, vol. 69, no. 6, 2019, pp. 2414–2426., doi:10.1002/hep.30320.

Amber Satz, PharmD Candidate, LECOM School of Pharmacy