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Approved Research

Effects of glucose-lowering drugs on cardiac arrhythmia, it's drivers and related outcomes

Principal Investigator: Dr Xinlin Zhang
Approved Research ID: 91907
Approval date: January 16th 2023

Lay summary

Type 2 diabetes mellitus is a leading cause of cardiac arrhythmias, including atrial fibrillation and ventricular arrhythmia, and sudden death. Glucose-lowering drugs have been rapidly developing and some of them, such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have showed good performance in reducing cardiovascular events, including arrhythmia. For example, SGLT2i was associated with a 20% reduction of atrial fibrillation risk in diabetic patients, at short-to-midterm follow-up. Therefore, it's important to assess the long-term effect of SGLT2i on atrial fibrillation occurrence, as well as to compare the effects of different glucose-lowering drugs.

Non-alcoholic fatty liver disease (NAFLD), one newly recognized driver of cardiac arrhythmia including atrial fibrillation, has surpassed the combined population of obesity and diabetes-the 2 traditional major risk factors for atrial arrhythmia. Depression and dementia, two common clinical outcomes of atrial fibrillation, are also neglected in current clinical practice. Whether glucose-lowering drugs have favorable effects on these new risk factors (NAFLD) and clinical outcomes (depression/dementia) remain unclear.

Therefore, the study aims to incorporate data from the UK Biobank, to evaluate the effect of different glucose-lowering drugs (including SGLT2i, GLP-1RA, metformin, dipeptidyl peptidase 4 inhibitors, sulfonylureas, and insulin, etc) on the risk of cardiac arrythmias, its drivers and related clinical outcomes.

  The project duration is estimated to be 36 months. These findings may help decide which glucose-lowering drug should be preferred in certain diabetic patients, such as those with arrhythmias and NAFLD/dementia. The study could also provide support for initializing new randomized trials to further confirm the effects of glucose-lowering drugs on cardiac arrhythmia.