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.

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Key information

Conditions

Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

19 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Seoul National University Hospital

Seoul, 110-144, South Korea

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Adults over 19 years
More than 10 years of diabetes
Low dose sulfonylurea use: Equivalent capacity 2 mg or less of glimepiride
Less than 7.5% of glycated hemoglobin for more than 6 months
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

Treatment and study plan

discontinuation of Sulfonylureas

Drug

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

Primary outcomes

the list of previously found candidate variants which are observed in the slufonylurea-dependent patients but not in the non-dependent patients

Time frame: 20 weeks

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.

Sponsors and collaborators

Lead sponsor

Seoul National University Hospital

Other

Registry information

Important dates

Study start: 2019
Primary completion: 2020
Study completion: 2020
First posted: Oct 11, 2019
Registry last updated: Dec 16, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed