Effects of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor, on blood glucose and plasma incretin and insulin responses to small intestinal glucose infusion, in healthy lean and obese subjects, and alone or in combination with metformin in patients with type 2 diabetes mellitus.
Royal Adelaide Hospital
36 participants
May 20, 2009
Interventional
Conditions
Summary
This study will determine whether the antidiabetic medicine, sitagliptin, has the capacity to increase intestinal hormones called glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), decrease blood glucose levels and reduce appetite in healthy subjects and people with type 2 diabetes. We will also determine, in the people with diabetes, whether these effects are enhanced when sitagliptin is given together with another diabetes drug, metformin.
Eligibility
Inclusion Criteria12
- Healthy lean subjects:
- Male Causcasians aged 18 – 70 years, age-matched to the obese subjects
- Body mass index (BMI) 19 - 25 kg/m2
- Healthy obese subjects:
- Male Causcasians aged 18 – 70 years
- Body mass index (BMI) 30 - 40 kg/m2
- Fasting blood glucose concentration < 5.6 mmol/L
- Type 2 diabetic patients:
- Male Causcasians aged 18 – 70 years
- Body mass index (BMI) 28 - 40 kg/m2
- Type 2 diabetes (World Health Organisation (WHO) criteria) managed by diet alone (i.e no oral hypoglycaemic drugs or insulin)
- Glycated haemoglobin = 6.0% and < 8.5%
Exclusion Criteria8
- History of gastrointestinal surgery (except appendicectomy)
- Medication which may affect gastrointestinal motor function, body weight or appetite
- Other significant illness, including epilepsy, cardiovascular or respiratory disease
- Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes per day
- Regular gastrointestinal symptoms (as assessed by a validated upper gastrointestinal symptom questionnaire)
- Autonomic nerve damage (as assessed by standardised cardiovascular reflex tests)
- Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests)
- For diabetic patients, inability to tolerate oral metformin 850 mg bd for a 7 day trial, to be completed at least 2 weeks prior to commencing the study.
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Interventions
Healthy lean and obese subjects will each undergo two studies (sitagliptin 100 mg oral versus control), in double-blind, randomised fashion, separated by 3 - 14 days. Patients with type 2 diabetes will be studied on 4 occasions each: twice during therapy with metformin 850 mg twice daily for 7 days (days 5 and 8, sitagliptin 100 mg oral or control), and twice during treatment with a matching placebo twice daily for 7 days, with a washout period of 14 days between treatment periods. In the diabetic patients, the order of both metformin and placebo, and sitagliptin and control, will be randomised, except that during the second metformin/placebo treatment period, the order of sitagliptin and control will be identical to the first treatment period. On each study day, glucose will be infused into the duodenum at 2 kcal/min from 0 to 120 min. Within each group (healthy lean, healthy obese, diabetic), each subjects acts as his own control, but comparison will also be made between groups.
Locations(1)
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ACTRN12608000433303