Combining Saxagliptin and Acarbose to Improve Postprandial Glycaemia in Type 2 Diabetes

Study Overview
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Brief Summary
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The proposed study is designed to evaluate (i) the effects of saxagliptin, with or without acarbose, on gastric emptying, postprandial glycaemia, and plasma intact GLP-1, insulin, C-peptide and glucagon after a high carbohydrate meal, and (ii) whether the magnitude of the effects of saxagliptin and/or acarbose is related to the rate of gastric emptying, in patients with type 2 diabetes.

Official Title
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Combining Saxagliptin and Acarbose to Improve Postprandial Glycaemia in Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Acarbose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet alone (i.e. no oral hypoglycaemic drugs or insulin) Body mass index (BMI) 20 - 40 kg/m2 Age 18 - 70 years Males and post-menopausal females (to control for the effect of the menstrual cycle on gut hormone secretion) Glycated haemoglobin A1c (HbA1c) ≥ 6.0% and ≤ 7.9% Haemoglobin above the lower limit of the normal range (i.e. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. >10mcg/L) Exclusion Criteria: Use of any medication that may influence gastrointestinal motor function, body weight or appetite Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) Other significant illness, including epilepsy, cardiovascular or respiratory disease Autonomic nerve damage (as assessed by standardised cardiovascular reflex tests [36]) Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests (> 2 times upper limit of normal range)) Allergy to vildagliptin or any other 'gliptin' Donation of blood within the previous 3 months Participation in any other research studies within the previous 3 months Females who are pre-menopausal Inability to give informed consent Vegetarians

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg saxagliptin + 100 mg acarbose<br>Acute dosing: 5 mg saxagliptin is given with water, 60 min before a test meal 100 mg acarbose is given with a test meal | Drug: Saxagliptin<br> <br> * Other names: Onglyza;Drug: Acarbose<br> <br> * Other names: Glucobay;|
| Experimental: 5 mg saxagliptin<br>Acute dosing: 5 mg saxagliptin is given 60 min before a test meal, | Drug: Saxagliptin<br> <br> * Other names: Onglyza;|
| Experimental: 100 mg acarbose<br>Acute dosing: 100 mg acarbose is given with a test meal | Drug: Acarbose<br> <br> * Other names: Glucobay;|
| No Intervention: control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood glucose concentrations at pre-defined intervals |  | -60,-10,0,30,60,90,120,180min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of incretin hormones at pre-defined intervals |  | -60,-10,0,30,60,90,120,180min | 
| Plasma concentrations of insulin at pre-defined intervals |  | -60,-10,0,30,60,90,120,180min | 
| Plasma concentrations of C-peptide at pre-defined intervals |  | -60,-10,0,30,60,90,120,180min | 
| Plasma concentrations of glucagon at pre-defined intervals |  | -60,-10,0,30,60,90,120,180min | 
| half-emptying time (T50) |  | 0-180min |