Sitagliptin and Glucagon Counterregulation

Study Overview
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Brief Summary
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To evaluate the effect of DPP-4 inhibition on glucagon counter-regulatory mechanisms at moderate hypoglycemia in metformin-treated subjects with T2DM

Detailed Description
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The glucagon response to mild (3.0 mmol/l) hypoglycemia with and without DPP-4 inhibition by sitagliptin will be evaluated in elderly subjects with metformin treated type 2 diabetes to explore whether DPP-4 inhibition affects glucagon counter-regulation.

Official Title
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The Effect of Sitagliptin on Glucagon Counterregulation and Incretin Hormones During Mild Hypoglycemia in Elderly Patients With Metformin-treated Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written consent has been given. Patients with metformin treated T2DM (metformin dose >0,5 g/day and stable during the preceding 3 months) Age >65 years. HbA1c 6.0-8.5% (43-67 mmol/mol; inclusive) at visit 1. Ability to complete the study Exclusion Criteria: A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly. Type 2 diabetes, positive GAD antibodies eGFR <60 ml/min Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 Any history of recent (<2 weeks) recurrent or severe hypoglycemic episodes. Liver disease such as cirrhosis or chronic active hepatitis History of coronary heart disease or heart failure class III or IV Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks. Treatment with growth hormone of chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1. Use of other investigational drugs at visit 1 or within 30 days of visit 1, unsuitable for the study

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 90 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sitagliptin first, then placebo<br>Sitagliptin treatment for four weeks, then washout for four weeks, then placebo for four weeks | Drug: Sitagliptin<br>* Sitagliptin 100 mg daily<br>|
| Other: Placebo first, then sitagliptin<br>Placebo for four weeks, then washout for four weeks, then sitagliptin for four weeks | Drug: Placebo<br>* Placebo one tablet daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon Counterregulation to Hypoglycemia | Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo | Four weeks treatment |