Pathophysiology of type 2 diabetes: A focus on the metabolic differences among southeast Asian, Chinese and Indian populations and how this impacts treatment.

The prevalence of type 2 diabetes has been rising in China, India and Southeast Asia for decades, challenging their healthcare systems. With region-specific determinants such as genetics, lifestyle transition and early-life environment, people with type 2 diabetes showed their unique phenotypes, including being, on average, younger in age, with lower BMI but higher percentage body fat mass, higher postprandial glucose and poorer beta-cell function at onset. These features invalidated the implementation of some trial evidence from the Caucasian population when informing guideline recommendations and clinical decision-making. For example, α-glucosidase inhibitors and DPP4 inhibitors, targeting postprandial glucose, showed greater effectiveness and acceptability in Chinese people with type 2 diabetes. The indispensable use of insulin in people with severely impaired beta-cell function is common in China, India and Southeast Asian countries but induces the accumulation of body fat mass, which further worsens the prognosis of the people. GLP-1 receptor agonists show strong weight-lowering effects and cardiovascular protection and provide additional benefits for Asian people compared to Caucasians with the same levels of BMI. Adding GLP-1 receptor agonists to people receiving insulin may neutralise the adverse effect of body weight gain. Clinicians and patients should consider the unique features of the population before making decisions, and policymakers should be aware of the pragmatic determinants during the implementation of the overseas evidence. The adoption of international trials to the region by adjusting their distinct features may improve the relevance of evidence and the treatment response at the individual level.