Non-alcoholic Fatty Liver Disease and Its Treatment

Effect of DPP-4I and Related Treatment on Non-alcoholic Fatty Liver Disease

Dipeptidyl peptidase-4 inhibitors (DPP-4I), key regulators of the actions of incretin hormones, exert anti-hyperglycemic effects in type 2 diabetes mellitus (T2DM) patients. A major unanswered question concerns the potential ability of DPP-4I to improve intrahepatic lipid (IHL) content in nonalcoholic fatty liver disease (NAFLD) patients. The aim of this study was to evaluate the effects of sitagliptin on IHL in NAFLD patients.

Study Overview

• Status: Completed
• Conditions: NAFLD
• Intervention / Treatment: Drug: Sitagliptin; Drug: Metformin; Drug: sitagliptin and metformin

Detailed Description

A prospective, 24-week, single-center, open-label, comparative study enrolled 68 Chinese NAFLD patients with T2DM. Subjects were randomly divided into 4 groups: control group who did not take medicine (14 patients); sitagliptin group who received sitagliptin treatment (100mg per day) (17 patients); metformin group who received metformin (500mg three times per day) (17 patients); and sitagliptin plus metformin group who received sitagliptin (100mg per day) and metformin (500 mg three times per day) (20 patients). IHL, physical examination (waist circumstances, WC; body mass index, BMI), glucose-lipid metabolism (fasting plasma glucose, FPG; hemoglobin A1c, Hb1A1c; triglycerides; cholesterol; alanine aminotransferase, ALT; aspartate aminotransferase, AST) were measured at baseline and at 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 30-70 years old
• fulfillment of the diagnostic criteria for T2DM by WHO in 1999 (HbA1c ranged from 7% to 10%, FPG < 11 mol/l, 2-hour blood glucose postprandial < 20mmol/l)
• Fulfillment of the diagnostic criteria for NAFLD according to the guidelines of the Chinese Medical Association in 2010. The IHL content was measured by using 1H-magnetic resonance spectroscopy (1H-MRS) quantitative detection, and the liver fat content of the enrolled subjects was more than 5.5%. The subjects included in this study had either no history of alcohol consumption or their alcohol intake was less than 70 g/week in males and less than 140 g/week in females. Liver transaminase and serum creatinine were less than two times the upper limit of normal

Exclusion Criteria:

• T2DM complicated with ketoacidosis, hyperosmolarity, acute and chronic infection ● serious heart, liver, kidney, lung disease, and liver damage
• alcoholic fatty liver
• drug use that influences glucose metabolism such as thiazide diuretics and hormones within three months
• Hypertension ≥ 180/110 mmHg
• gastrointestinal disease or absorption dysfunction
• recent trauma, surgery, or other conditions resulting in an increased stress response within the past three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; did not take medicine
Experimental: DPPVI; received sitagliptin treatment (100mg per day)	Drug: Sitagliptin; sitagliptin treatment (100mg per day)
Experimental: metformin; received metformin (500mg three times per day)	Drug: Metformin; metformin group who received metformin (500mg three times per day)
Experimental: metformin +DPPVI; received sitagliptin (100mg per day) and metformin (500 mg three times per day)	Drug: sitagliptin and metformin; sitagliptin plus metformin group who received sitagliptin (100mg per day) and metformin (500 mg three times per day) (20 patients); Other Names: DPP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intrahepatic lipid (IHL)	hepatic steatosis	24weeks

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital

Publications and helpful links

General Publications

• Wang X, Zhao B, Sun H, You H, Qu S. Effects of sitagliptin on intrahepatic lipid content in patients with non-alcoholic fatty liver disease. Front Endocrinol (Lausanne). 2022 Aug 22;13:866189. doi: 10.3389/fendo.2022.866189. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: July 24, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: 085348

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No