Grant: Canada Postdoctoral Research Award (CPRA) program

Drugs like Ozempic have substantially improved health outcomes for individuals living with obesity and diabetes. These drugs not only produce major weight loss and lower blood sugar levels, but they can also treat a form of heart disease in diabetes that is defined by an inability of the heart to relax and is a major cause of death in diabetics. These drugs function primarily by mimicking the actions of a natural hormone in the body that engage proteins in the body referred to as GLP-1 (glucagon-like peptide-1) receptors. Newer drugs like Mounjaro mimic the actions of this same hormone but also mimic a related hormone that engages a similar protein in the body referred to as the GIP (gastric inhibitory peptide) receptor. In doing so, Mounjaro has even greater anti-diabetic and weight loss efficacy. Of interest, Ozempic has been shown to also improve heart function in people living with obesity/diabetes, however there is unclear and conflicting evidence surrounding the impact of activating the GIP receptor in terms of heart health. Our study aims to bridge this gap by investigating the independent and interactive effects of GLP-1 and GIP receptor activation on heart health in the context of obesity and diabetes, by comparing Mounjaro against Ozempic. In our study, we will use a unique genetically modified mouse model to separate the effects of GLP-1 and GIP receptor agonism on heart function after inducing the development of diabetes. Using ultrasound, we will directly measure heart function in mice treated with either Mounjaro or Ozempic. We anticipate that activating the GIP receptor has harmful effects on heart function, and thus Ozempic will overall have better actions on heart health than Mounjaro, despite the latter causing greater weight loss. Thus, our study is critical to understand the precise outcomes of these drugs on heart health in people living with obesity/diabetes, which may have major impacts on clinical practice in our healthcare system.