Genetic Variants Replication Study Associated With Dependence on Sulfonylurea in Participants With Type 2 Diabetes

This study was designed to reproduce candidate single nucleotide variants found by whole exome sequencing in some type 2 diabetic patients dependent on sulfonylurea in a separate patient group. The validation of the dependence-related variations performed in this study is expected to help decision-making in the clinical use of sulfonylurea in the future.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: discontinuation of Sulfonylureas

Detailed Description

Sulfonylurea, one of the oral hypoglycemic agents, is the oldest and most widely used drug. The use of sulfonylurea was overwhelming compared to metformin especially in East Asia, where insulin secretion was notable during the pathophysiology of type 2 diabetes. However, sulfonylurea causes hypoglycemia and weight gain, increases cardiovascular disease and mortality compared to other oral preparations. With the recent development of other oral hypoglycemic agents for lowering blood glucose without the risk of hypoglycemia and with cardiovascular protection, sulfonylurea is in a decreasing state of use worldwide.

But some patients tend to be highly dependent on sulfonylurea for blood glucose control. It suggests that there will be a group of patients whose the action of sulfonylurea is strongly influenced by genetic factor, since insulin secretion of pancreatic beta cells is very hereditary, genetic variations that increase the risk of type 2 diabetes are found mainly in genes related to beta cell dysfunction rather than insulin resistance, and the more risk variants of type 2 diabetes, the less likely the effect of sulfonylurea is.

The investigators had performed whole exome sequencing in patients showing dependence on sulfonylurea and identified tens of candidate variants.

In this study, the investigators will select patients with dependence on sulfonylurea by prospective intervention (by discontinuing and resuming sulfonylurea) and perform genetic tests.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-144
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Among patients with type 2 diabetes who visited Seoul National University Hospital endocrinology outpatient clinic, all of criteria (1)-(4) are satisfied

1. Adults over 19 years
2. More than 10 years of diabetes
3. Low dose sulfonylurea use: Equivalent capacity 2 mg or less of glimepiride
4. Less than 7.5% of glycated hemoglobin for more than 6 months
5. estimated glomerular filtration rate > 50 mL/min/1.73㎡

Exclusion Criteria:

• Type 1 diabetics
• Insulin user
• Patients diagnosed with cardiovascular disease, cancer, and other critical illness within 6 months before the study
• Patients with severe hypertension
• Patients with treatment or diseases that may have a significant effect on blood glucose levels, such as glucocorticoids and thyrotoxicosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sulfonylurea-dependent; Sulfonylurea is replaced by alternative oral hypoglycemic agent.

Drug: discontinuation of Sulfonylureas; Discontinuation of sulfonylurea, alternative drug administration.; If there is a significant increase in blood glucose, it is considered as a sulfonylurea-dependent patient. Discontinue the alternative drug and resume the sulfonylurea, and monitor for 12 weeks or until stabilization of blood glucose at short intervals.; if blood glucose levels are within optimal range after replacement of sulfonylureas with other agents, the patient is regard as non-SU-dependent; Other Names: other oral anti-diabetics instead of sulfonylureas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the list of previously found candidate variants which are observed in the slufonylurea-dependent patients but not in the non-dependent patients	Dependency on sulfonylurea-dependency is determined according to changes in HbA1c by use of sulfonylurea. The 'previously found candidate variants' are the results from whole exome sequencing in patients showing dependence on sulfonylurea as a screening before.	20 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Hye Seung Jung, MD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2019
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 13, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Sulfonylurea
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Physiological Effects of Drugs; Hypoglycemic Agents
• Other Study ID Numbers: SU

Drug and device information, study documents

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