Effects of Ipragliflozin on Excessive Fat in Type 2 Diabetes Patients With Non-alcoholic Fatty Liver Disease Treated With Metformin and Pioglitazone

June 22, 2017 updated by: Yonsei University
In this study, the investigators investigate beneficial effects of ipragliflozin, newly developted SGLT2 inhibitor, on reduction in visceral fat area and degree of fatty liver in subjects with T2DM when added to metformin and pioglitazone therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) agonist increase insulin sensitivity in peripheral tissue and liver by protecting non-adipose tissues against excessive lipid overload and by balancing the secretion of adipocytokines.

However, PPARγ is a key transcription factor that induces the differentiation adipocyte maturation and stimulates the induction of enzymes involved in lipogenesis. As a result, the effect of pioglitazone is generally accompanied by weight gain and an increase in amount of subcutaneous fat.

Obesity would coexist with fatty liver disease and both conditions aggravate hyperglycemia in diabetes. According to recent study, up-regulated PPARγ expression in liver was reported in obesity with hepatic steatosis which implies pioglitazone might induce fatty liver disease.

A novel oral antidiabetic drug, sodium glucose cotransporter 2 (SGLT2) inhibitor reduces renal glucose reabsorption and increasing renal glucose excretion thereby promoting energy loss. As a result, it prevents weight gain and fluid retention which might counteract the unfavorable effects of pioglitazone treatment.

No study has been conducted on the additional effect on obesity and fatty liver of ipragliflozin in T2DM patients treated with pioglitazone and metformin.

In this study, the investigators investigate beneficial effects of ipragliflozin, newly developted SGLT2 inhibitor, on reduction in visceral fat area and degree of fatty liver in subjects with T2DM when added to metformin and pioglitazone therapy.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Yonsei University College of Medicine, Department of internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 2 diabetic patients
  • Diagnosed as NAFLD
  • Age of 20~75
  • On metformin + pioglitazone treatment with stable dose for at least 8 weeks
  • Adequate glycemic control: HbA1c ≤ 9.5%
  • Overweight & obese: BMI ≥ 23 kg/m2
  • Subject is male, or subject is female who is highly unlikely to conceive
  • Understands the study procedure, alternatives, and risks and voluntarily agrees to participate by giving written informed consent

Exclusion Criteria:

  • Type 1 diabetes, Secondary diabetes, gestational diabetes
  • Heavy alcoholics (men ≥210 g of alcohol per week, women ≥140 g of alcohol per week)
  • Underlying chronic liver disease (hemochromatosis, liver cell carcinoma, autoimmune liver disease, liver cirrhosis, chronic viral hepatitis [except hepatitis B carrier], Wilson's disease)
  • Patients on medication causes hepatic steatosis (e.g.amiodarone, methotrexate, tamoxifen, valproate, corticosteroids, etc)
  • Allergy or hypersensitivity to target medication or any of its components
  • Renal failure, moderate or severe renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m2), or ongoing dialysis
  • Abnormal liver function (AST/ALT > x10 upper normal limit)
  • On taking weight loss medication
  • History of alcohol or drug abuse in the previous 3 months
  • Premenopausal women who are nursing or pregnant
  • Human immunodeficiency virus (HIV) or human immunodeficiency virus (AIDS)
  • Diabetic ketoacidosis
  • Severe infection, severe trauma

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group IMP
Group IMP (Ipragliflozin with Metformin with Pioglitazone)
Drug: Ipragliflozin
Patients treated with ipragliflozin (50 mg/day) as add on therapy to metformin and pioglitazone dual therapy (triple therapy) for 6 months. During whole periods of study, subjects are educated for nutrition and exercise. (Experimental Group)
Other Names:
  • Suglat®
Active Comparator: Group MP
Group MP (Metformin with Pioglitazone)
Drug: metformin with pioglitazone
Patients maintain metformin and pioglitazone dual therapy for 6 months. During whole periods of study, subjects are educated for nutrition and exercise. (Control group)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes in visceral fat area
Time Frame: 6 months
The visceral fat area is measured by dual-energy x-ray absorptiometry (DEXA) at baseline and after 6 months treatment
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in subcutaneous fat area
Time Frame: 6 months after treatment
The subcutaneous fat area is measured by dual-energy x-ray absorptiometry (DEXA) and fat computed tomography (CT) at baseline and after 6 months treatment.
6 months after treatment
Changes in liver fat
Time Frame: 6 months after treatment
Changes in the degree of fatty liver is measured by fibroscan using controlled attenuation parameter (CAP) score.
6 months after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yonsei University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2016

Primary Completion (Actual)

June 7, 2017

Study Completion (Actual)

June 7, 2017

Study Registration Dates

First Submitted

August 18, 2016

First Submitted That Met QC Criteria

August 18, 2016

First Posted (Estimate)

August 23, 2016

Study Record Updates

Last Update Posted (Actual)

June 23, 2017

Last Update Submitted That Met QC Criteria

June 22, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4-2015-1115

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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