Variation in Sulphonylurea Response in Type 2 Diabetes

Study Overview
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Brief Summary
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The study hypothesis is that people who respond well to sulphonylureas have a different underlying cause for their diabetes than people who respond poorly to this medication. We are using two approaches to study this. In one approach we look at people who have previously responded well or poorly, confirm this by rechallenging them with a sulphonylurea drug, and then looking at how well they produce insulin in response to glucose and an intravenous sulphonylurea called tolbutamide. The second approach identifies people with a certain genetic predisposition to diabetes (due to changes in the TCF7L2 gene) and then looks at how well they respond to sulphonylurea medication.

Official Title
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The Use of Glycaemic Response to Sulphonylureas as a Tool to Investigate Type 2 Diabetes Pathophysiology

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: gliclazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Age >35 and < 70 Age of diabetes diagnosis >35 and <70 White European Pre-SU HbA1c <=10% HbA1c (on treatment) <= 9% No myocardial infarction or Acute coronary syndrome in previous year No stroke or transient ischaemic attack in previous year No or stable (background) retinopathy (no unscheduled laser treatment in the last 6 months) eGFR > 60mls/min No Proteinuria >30mg/dl on multistix 10SG No active foot ulceration or infection Liver ALT ≤ twice the upper limit of the reference range Contactable by telephone Exclusion Criteria: Type 1 diabetes HbA1c >10% prior to commencing SU HbA1c>9% on SU treatment Recent MI or Stroke within last 12 months Pre-proliferative or proliferative retinopathy eGFR<60 ml/min Proteinuria >30mg/dl on multistix 10SG Active foot ulceration or infection Liver ALT > twice the upper limit of the reference range Female planning to conceive within the study period Any other significant medical reason for exclusion as determined by the investigator

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Withdrawal of sulphonylurea for 6 weeks, then re-introduction for 6 weeks, assessed by fasting glucose and HbA1c | Drug: gliclazide<br>* Gliclazide 80mg bd for 6 weeks<br>* Other names: Diamicron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c reduction |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin secretory response to glucose and tolbutamide |  | acute | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sulphonylurea, Pharmacogenetics