None listed
Conditions
Brief summary
Patients with type 2 diabetes are at high risk of cardiovascular disease. Treatments targeted at lowering glucose may reduce the risk of cardiovascular disease, however other approaches are needed as patients remain at an elevated residual risk of cardiovascular events. There is evidence that fluctuation in blood pressure (blood pressure variability) is an important risk factor for cardiovascular disease, such that substantial changes over time are detrimental and lead to an increased risk of cardiovascular disease. Metformin is a drug that has been used for diabetes for many years, though the mechanism of action remains incompletely understood. Early studies with this drug suggested that this particular agent was effective at reducing cardiovascular events and there is some evidence that metformin can modify both blood pressure, and gut responses following a meal. We are interested in looking to see whether metformin could reduce blood pressure fluctuations induced throughout the day, and in particular following meals. Information from this study will help guide further research into mechanisms behind and potential novel approaches to cardiovascular disease and blood pressure in diabetes. Given recent interest in the bacteria in the gut and how this influences health and blood sugar control, we will also look at the effect of metformin on bugs in the gut (microbiome).
Interventions
This is a randomised double-blind cross-over placebo-controlled trial evaluating 2 treatment periods with a 2 week wash-out, with a total study duration of 4 weeks.: i) acute effects following 1 dose of metformin (850 mg) and ii) chronic effects following 1 week of treatment with metformin 850 mg twice daily. As for our previous work, randomisation will be undertaken using a random number generator and conducted through the RAH Pharmacy Department, who will also provide a placebo for metformin.
This is a randomised double-blind cross-over placebo-controlled trial evaluating 2 treatment periods with a 2 week wash-out, with a total study duration of 4 weeks.: i) acute effects following 1 dose of metformin (850 mg) and ii) chronic effects following 1 week of treatment with metformin 850 mg twice daily. As for our previous work, randomisation will be undertaken using a random number generator and conducted through the RAH Pharmacy Department, who will also provide a placebo for metformin. Metformin and matching placebo will be capsules. The 24-hour ABP monitor consists of a cuff which fits around the upper arm and is the same cuff that is usually used to measure blood pressure. The cuff is attached to a monitor, which is about the size of a large smart phone which records the readings. The participant will be asked to record the time of meals, exercise and sleep while wearing the monitor. The ambulatory blood monitor may be associated with slight discomfort as blood pressure readings are taken every 15-30 minutes during the 24 hour period (but only hourly overnight). Following screening and consent (visit 1), patients will present to our institution on 7 occasions over 3 weeks for a total of 8 visits. Week 1 (metformin or placebo) will require a visit to be fitted for the baseline ambulatory blood pressure (ABP) monitor (visit 2) and subsequently baseline gastric emptying/cardiovascular response post glucose load (visit 3) with return of the 24-hour ABP monitor and stool sample. Visit 4 will include fitting of the ABP monitor and visit 5 chronic gastric emptying/cardiovascular response post glucose load on day 7 and return of the ABP monitor and stool sample. This will be followed by 2-week washout. Final week as per week 1 with the alternative treatment - visit 6 for acute gastric emptying study, visit 7 for fitting of ABP monitor and visit 8 for return of ABP monitor and stool sample and final gastric emptying study. Faecal sample collection tubes/instructions will be given at the same time as ABP fitting and returned at the same time of return of ABP. Adherence will be monitored by return of pre-filled Webster packs at the conclusion of the study.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet only Body mass index (BMI) 25 - 35 kg/m2 Males and females, aged 40-80 years Glycated haemoglobin (HbA1c) 6- 8.5% Haemoglobin above the lower limit of the normal range (ie. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. >30ng/mL for men and >20mg/mL for women) Patients on stable doses of antihypertensives will be included.
Exclusion criteria
Use of any medication that may influence gastrointestinal motor function, body weight or appetite (opiates, anticholinergics, levodopa, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, prucalopride, or erythromycin) 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 Impaired renal or liver function (as assessed by calculated creatinine clearance < 60 mL/min or abnormal liver function tests (> 2 times upper limit of normal range)) Donation of blood within the previous 3 months Participation in any other research studies within the previous 3 months Inability to give informed consent Female participants who are not on long acting contraception Previously unable to tolerate metformin or treatment with metformin within the past week.
Outcome results
None listed