None listed
Conditions
Brief summary
Antipsychotic drugs are the second most prescribed medications in New Zealand for the treatment of schizophrenia and other forms of psychosis (Pharmac annual review). Over 40,000 people are prescribed one of the four Pharmac funded second generation antipsychotic drugs (SGAs) clozapine, risperidone, quetiapine or olanzapine, at a cost of $61.6 million NZD annually (Pharmac 2009 annual review). However, the most effective antipsychotic drugs, clozapine and olanzapine, greatly increase the risk of weight gain and type 2 diabetes, and so further increase morbidity, mortality and health care costs. It was previously thought the weight gain was the cause of the type 2 diabetes in these patients but we have recently shown in animal models that these drugs directly impair glucose metabolism. This occurred via suppression of Glucagon-Like-Peptide-1(GLP-1) levels and these defects could be overcome by restoration of GLP-1 signalling. Given the large number of patients on SGA medications it is clearly very important to properly understand how these drugs affect glucose metabolism and what the most appropriate therapies for this are. We aim to determine whether regulation of the GLP-1/glucagon axis is responsible for the effects SGAs have on glucose metabolism we propose a clinical trial in healthy subjects to test the effect of acute exposure (single dose or 8-day) of olanzapine on glucose tolerance, insulin resistance and hepatic glucose output. We will determine whether this is associated with changes in glucagon and GLP-1 levels (based on the hypothesis developed from our animal data). We will go on to determine whether drug induced impairments in glucose metabolism can best be overcome by restoration of GLP-1 signalling using currently available drugs.
Interventions
patients will be randomised to one of the four groups:
group 1:
8 days use of olanzapine 10mg daily (oral tablets)
group2:
8 days use of olanzapine 10mg daily (oral tablets) +
metformin oral tablets 1g twice a day during the same 8 day period
group 3:
8 days use of olanzapine 10mg daily (oral tablets) + sitagliptin oral tablets 100mg daily during the same 8 day period
group 4:
8 days use of olanzapine 10mg daily (oral tablets) + exenatide (subcutaneous injection) 10micrograms twice a day d
patients will be randomised to one of the four groups: group 1: 8 days use of olanzapine 10mg daily (oral tablets) group2: 8 days use of olanzapine 10mg daily (oral tablets) + metformin oral tablets 1g twice a day during the same 8 day period group 3: 8 days use of olanzapine 10mg daily (oral tablets) + sitagliptin oral tablets 100mg daily during the same 8 day period group 4: 8 days use of olanzapine 10mg daily (oral tablets) + exenatide (subcutaneous injection) 10micrograms twice a day during the same 8 day period
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
BMI 20-25 healthy male volunteers
Exclusion criteria
family or personal history of diabetes, schizophrenia. current regular medications. smoker
Outcome results
None listed