New treatment for type 2 diabetes helps over 2 million patients
Dapagliflozin is a new therapy for diabetes that reduces renal glucose re-uptake
Diabetes is a group of diseases in which blood glucose is too high for a prolonged period of time. Type 2 diabetes, sometimes referred to as ‘adult-onset diabetes’, is characterised by high levels of blood glucose, insulin resistance and insufficient insulin, and is often associated with being overweight. The condition affects over 450 million people globally and can cause major complications in the eyes, kidneys, nerves, heart and blood vessels. In consequence, diabetes accounts for up to 10% of healthcare costs in western society.
Current treatments for diabetes have limitations of effectiveness and some have side effects such as weight gain or nausea. New treatments are therefore necessary to tackle this lifelong condition.
Dapagliflozin is a new therapy for diabetes that reduces renal glucose re-uptake which results in excretion of excess glucose in the urine, facilitating weight loss and reducing blood pressure. Prior to launch, new therapies (including dapagliflozin) must undergo clinical trials to assess their effectiveness and any potential side effects.
Clifford Bailey is a Professor of Clinical Science at Aston University’s School of Life and Health Sciences. He is Head of Diabetes Research within the Biosciences Research Group which focuses on interventional approaches against insulin resistance as well as the development of new agents to treat diabetes and obesity. The group also has particular expertise with trials involving glucose-lowering medicines.
Based on his specialist experience, Professor Bailey was selected as principal investigator for the design of trials to assess the efficiency, safety profile and pharmacodynamics properties of dapagliflozin. During this project, he collaborated with a range of institutions in Brazil, the USA and Canada.
Development of new drugs requires critical evaluation in patients in so-called ‘Phase III Trials’. These trials need to establish drug safety, determine the therapeutic profile and demonstrate that the drug complies with rigorous standards of medicines regulation.
Professor Bailey’s role was fundamental to the design, conduct, analysis and communication of these pivotal clinical trials. These trials were randomised, double blinded and collectively involved over 1,000 patients.
Subsequent clinical studies exploring the mode of action and clinical opportunities for use of dapagliflozin as a glucose-lowering therapy for type 2 diabetes have also been undertaken.
The varied and progressive nature of type 2 diabetes requires use of different medicines in different individuals at different disease stages. As a result, dapagliflozin was synthesised by pharmaceutical company BristolMyersSquibb (BMS) to achieve selective inhibition of sodium/glucose co-transporter-2 (SGLT-2). By inhibiting SGLT-2, dapagliflozin reduces excess glucose in the blood through decreased reabsorption of glucose filtered by the kidneys. This increases the elimination of glucose in the urine.
The clinical research provided sufficient primary evidence required to show the efficiency and safety profile of dapagliflozin to be used as a suitable medicine for the treatment of type 2 diabetes, both as a monotherapy and in combination with metformin.
The impact of research led by Professor Bailey is demonstrated through the regulatory approval of dapagliflozin and the successful introduction of the medicine to treat more than 5 million patients with type 2 diabetes.
Dapagliflozin was formally launched within the European Union (EU) in 2012 and has since then been approved for routine clinical use in Europe, North America and most other regions of the world.
Assessment of the clinical trials by the National Institute for Health and Care Excellence (NICE) determined that dapagliflozin offered improved management of type 2 diabetes. This leads to enhanced patient quality of life by reducing complications that arise as a result of the condition. This in turn will impact hospital admissions, providing anticipated cost-benefits to the NHS and other healthcare systems.
Based on work from Aston, dapagliflozin can also be used as an additional therapy for patients on other glucose-lowering drugs. This takes advantage of studies showing that dapagliflozin can be combined successfully with other drugs such as metformin, as well as insulins.
For patients already on insulin, the addition of dapagliflozin can improve glucose control without weight gain.
Additionally, dapagliflozin has been approved as an oral agent to assist patients who have poorly controlled type 1 diabetes. This shows that dapagliflozin can be used effectively to support treatment of type 1 diabetes, as well as type 2 diabetes.
Whilst some other treatments for diabetes lead to weight gain, the clinical trials showed that dapagliflozin is able to improve body weight control and blood pressure control in type 2 diabetes patients. This was seen in a two year follow up of 5,800 patients receiving dapagliflozin during the first year of availability in the UK.
Based on studies designed with expertise from Aston University, dapagliflozin has become established as a ‘first in class’ agent to improve glucose control in people with diabetes, thereby advancing treatment options, helping to reduce the risk of complications and improving the quality of life.
As the prevalence of diabetes is increasing, it is necessary to find new and better treatments for this lifelong condition.