A newer pillar of GDMT (Goal Directed Medical Therapy) is the Sodium glucose transport 2 (SGLT2) inhibitors. They were initially introduced as anti-diabetic medications. While effective in managing diabetes, a serendipitous observation from these studies was there were cardiovascular outcomes, specifically survival benefits in patients with type 2 diabetes mellitus who had heart failure with reduced ejection fraction (HFrEF). Further subgroup analyses revealed that these benefits were observed in non-diabetic patients with HFrEF. This was followed by large clinical trials that demonstrated SGLT2 inhibitors reduce cardiovascular mortality and heart failure hospitalizations in patients regardless of whether they have diabetes or don’t. This resulted in their incorporation as the fourth pillar of GDMT for HFrEF patients. More recent studies have extended these benefits to non-diabetic patients with Heart Failure with preserved ejection fraction (HFpEF), leading these agents to be approved for HFpEF patients. There are side effects SGLT2 inhibitors including diuresis from the glycosuria that results from these drugs. This glycosuria can transiently cause volume depletion and elevations in creatinines as well as urinary tract infections which are more common in women and are a reason to halt SGLT2 therapy.