Use of novel glucose-lowering therapies in novel populations with type 2 diabetes

The phenotype of T2D is rapidly evolving due to increasingly sedentary lifestyles and unhealthy eating behaviours. Many individuals are diagnosed with T2D at a younger age. This presents unique challenges including early onset of complications and impaired physical function. Experts agree that the overall aim of T2D management should be to maintain optimal glycaemic control and avoid complications while achieving good quality of life and functional independence with due consideration of social determinants of health. Consequently, there is an emerging need to encourage use of “newer” glucose-lowering therapies (GLTs), which confer both glycaemic and metabolic benefits, in diverse populations.

The focus of my thesis is to explore the use of “newer” or novel agents; namely sodium–glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), in diverse T2D populations which have not been focus of much research. These include;

• young-onset T2D

• people with impaired physical function

• people who fast during Ramadan

• people who had COVID-19 infection

The use of novel GLTs is expected to improve metabolic and functional outcomes for these populations.

The initial plan of my PhD was to focus on the impact of dapagliflozin, an SGLT2i, on physical function in people with T2D, through a randomised-controlled trial (RCT). However, this was adversely impacted by the COVID-19 pandemic. Recruitment was delayed by ~12 months and when it began, targets were difficult to achieve due to staffing issues and social distancing restrictions. Thus, it was agreed to undertake additional projects focusing on use of novel therapies in novel populations. Undertaking this additional work meant acquiring new skills, expanding knowledge and networking with external peers. As a result, this thesis represents large body of diverse but interconnected work which has been either published or presented at conferences.

I have highlighted my contributions in individual chapters.