PhD Scholarship

QIMR Berghofer Medical Research Institute

PhD Projects with Clinical Trials and Biostatistics Unit - QIMR Berghofer Medical Research Institute

Topic: Exploring the cardiometabolic effects of treatment with GLP-1R agonists in type 2 diabetes patients
International collaborators: Bristol-Myers Squibb and Amylin Pharmaceuticals LLC, USA

Project description:

Lifestyle modifications in conjunction with anti-diabetes medications can produce near-normal blood glucose concentrations in patients with type 2 diabetes mellitus (T2DM). As these patients have increased cardiovascular morbidity and mortality, treatment strategies should also address the cardiovascular aspects of the disease, including body weight, blood pressure (BP) and lipids. Since the prevalence of these abnormalities is increasingly secondary to poor diet and sedentary lifestyles and because most patients with T2DM are overweight / obese, clinicians are encouraged to help patients reduce body weight while correcting hyperglycaemia by selecting treatment options that improve both parameters. Synthetic GLP-1 receptor agonists (GLP-1R agonists) represent promising new areas of research and therapeutics in the struggle not only against T2DM but also against the cardiovascular morbidity and mortality associated with T2DM. Two approved and marketed GLP-1R agonists are 'exenatide' and 'liraglutide'. These drugs have demonstrated their ability to significantly reduce the glucose level and body weight, and maintain lower rate of hypoglycaemia, compared to existing oral anti-diabetes drugs (OADs) and insulin.

Although some extra-glycaemic effects (including chronotropic and hypertensive effects) of GLP-1R agonists have been observed in higher-animal models and human studies, little is understood about the background mechanism of cardiometabolic effects of this class of drug. Also the long-term cardiovascular effect of GLP-1 receptor activation in humans is not yet known.

Combining patient-level data from several randomized clinical trials (n~2400) comparing the safety and efficacy of GLP-1R agonists with other anti-diabetes treatments, and also using a large population level clinical and event data (n~1million), the aims of this study are to:

1. Determine the possible effects and clinical significance of glucose control and weight loss longitudinally on blood pressure, pulse pressure and heart rate in patients treated with GLP-1R agonists;
2. Explore the long-term effects of weight loss and glycaemic control longitudinally on cardiovascular events in patients treated with GLP-1R agonist, compared with other anti-diabetes treatments;
3. Evaluate the individual and interactive effects of longitudinal changes in various risk factors on the incidence and rate of hypoglycaemia - compared between GLP-1R agonists and other anti-diabetes treatments;
4. Explore the long-term effects of treatment with GLP-1R agonists on lipid profiles, and to determine if there exists any interaction of early weight reduction and glycaemic control on lipid profile.

Selection criteria:

BSc or MSc in Statistics or Clinical Epidemiology, with some research experience;
Interest in clinical research, especially in diabetes and metabolic diseases;
Strong motivation to conduct independent research in the field of clinical biostatistics;
Excellent programming knowledge with software, e.g. R & SAS;
Ability to work independently and take responsibility of a program of work;
Excellent written communication skills.

Contact:

Interested applicants may contact Professor Sanjoy Paul, Head of the Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, and the Principal Investigator in this project. Email: sanjoy.paul@qimrberghofer.edu.au