Reducing high blood pressure and improve heart and kidney health with antidiabetic medication

Doctor Lakshini Herat, University of Western Australia

Postdoctoral Fellowship

Years funded: 2025 - 2027

Understanding how new antidiabetic treatments reduce high blood pressure and improve heart and kidney health

Sympathetic Nervous System (SNS) activation is one of the major drivers of Resistant Hypertension (RH), a condition characterised by high blood pressure that does not respond well to antihypertensive medicines. RH affects ~10-15% of patients diagnosed with hypertension, significantly increasing the risk of serious cardiorenal problems. This risk is further increased by obesity and extra fat deposition around vital organs (such as heart, kidney and liver) and is likely mediated via the SNS. The development of new-generation anti-diabetic drugs, such as Mounjaro (Tirzepatide), offers major weight loss benefits and cardiorenal protection. Yet the effects of Mounjaro on SNS activity, fat around vital organs and its implications for cardiorenal protection is not known.

Utilising our unique high blood pressure mouse model, which features a hyperactivated SNS and is fed a high-fat diet (thereby closely mimicking the human scenario), my research study will focus on understanding how treatments like Mounjaro may control the SNS, BP and organ specific fat, thereby protecting the heart and kidneys from damage. I will also explore whether the effects of Mounjaro can be further enhanced by adding an SGLT2 inhibitor known to reduce SNS activity and exerting various cardiorenal and organ protective effects independent of glucose control. Consequently, I seek to investigate the synergistic effects of these treatments in reducing the burden of cardiorenal disease by specifically targeting the SNS, BP and organ specific fat.

My work forms the basis for a highly feasible 2-year plan that may pave the way for similar studies in humans, investigating the use of several medications in low doses and their presumed combined beneficial effects in reducing the SNS activity and thereby providing organ protection. I will capitalise on our unique preclinical mouse model and the expertise of our team and collaborators brought together towards a holistic, future-centric approach aimed at understanding the use of “smart combination therapy” of currently existing anti-diabetic medications for the prevention and treatment of cardiorenal disease.