Sodium-glucose co-transporter 2 inhibitors induced polycythemia and risk of cardiovascular events

Sodium glucose co-transporter 2 (SGLT2) inhibitors are medicines that increase the amount of sodium ("salt") and glucose ("sugar") that are removed from the body in urine, and improve kidney function in heart failure, type 2 diabetes (a condition where blood sugar level is high) and chronic kidney disease. Beyond these effects, SGLT2 inhibitors stimulate the production of red blood cells i.e., the cells that transport oxygen to the tissues. Such production of red blood cells is a good thing in many conditions e.g., anemia, where patients who have low counts of red blood cells.

However, among patients with a predisposition for having elevated red blood cell counts e.g., smokers or patients with lung diseases, SGLT2 inhibitors may cause abnormal red blood cells elevation, a condition called "polycythemia". Polycythemia may be inherited genetically affecting around 22 people per 100,000 population, but can also arise as a result of other conditions that cause low oxygen levels in the blood such as, smoking and lung disease. Polycythemia usually presents as a raised hemoglobin level (an iron-rich protein in red blood cells that carries oxygen from the lungs around the body) in routine blood analysis and it can increase the risk for thromboembolic (blood clotting) events as, for example, pulmonary embolism (blood clot in the lungs). Therefore, there is a need to understand better the incidence of polycythemia associated with the use of SGLT2 inhibitors, the risk factors predisposing to its occurrence, and whether its occurrence increases the risk of thromboembolic events.

The aims of the study are to investigate the proportion of patients who develop polycythemia under SGLT2 inhibitor treatment, the risk factors for polycythemia, and whether the presence of polycythemia increases the risk of cardiovascular events such as blood clots in the blood vessels. This research will be conducted using data from placebo-controlled randomized trials (trials where some patients are given an inactive medicine), because it is the most reliable way of determining whether, compared to placebo, SGLT2 inhibitors increase the risk of thromboembolic events in a large and diverse population.