From the Guidelines
SGLT2 inhibitors should be used in patients with type 2 diabetes for their cardiorenal protective effects, with their impact on cholesterol levels being a secondary consideration, as they provide significant benefits in reducing heart failure hospitalizations, cardiovascular mortality, and progression of kidney disease, despite potential slight increases in LDL cholesterol 1. The primary role of SGLT2 inhibitors, such as empagliflozin, canagliflozin, and dapagliflozin, is to reduce cardiovascular disease and heart failure outcomes in people with diabetes, particularly those with increased cardiovascular risk or established cardiovascular disease 1.
- Key benefits of SGLT2 inhibitors include:
- Reduction in hospitalization from heart failure by 33-35% in people allocated to these medications, regardless of prior history of heart failure 1
- Reduction in cardiovascular mortality and hospitalization for heart failure by 17%, consistent across multiple study subgroups regardless of a prior history of heart failure 1
- Prevention of incident heart failure in asymptomatic people with type 2 diabetes at risk or with established cardiovascular disease 1 While SGLT2 inhibitors may have modest effects on cholesterol profiles, including small increases in HDL and LDL cholesterol, their overall impact on cardiovascular risk remains positive due to their significant cardiorenal protective effects 1.
- The cholesterol changes associated with SGLT2 inhibitors occur through complex mechanisms involving altered lipid metabolism when the kidneys excrete glucose, but these effects should not deter their use when indicated for glycemic control and cardiorenal protection in type 2 diabetes 1. For patients concerned about cholesterol management, SGLT2 inhibitors should be used as part of a comprehensive approach that may include statins as the primary cholesterol-lowering therapy, prioritizing their cardiorenal benefits while managing cholesterol levels appropriately 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Role of SGLT2 Inhibitors in Managing Cholesterol Levels
- SGLT2 inhibitors have been shown to improve various metabolic parameters, including lipid profile, in patients with type 2 diabetes 2.
- The mechanisms by which SGLT2 inhibitors improve cardiovascular outcomes appear to be hemodynamic effects through osmotic diuresis and natriuresis, rather than glucose-lowering or anti-atherosclerotic effects 2.
- Clinical trials have demonstrated that SGLT2 inhibitors can reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes, including those with high cardiovascular risk 3, 4, 5.
Effects on Cholesterol Levels
- SGLT2 inhibitors have been shown to improve lipid profiles, including reductions in low-density lipoprotein (LDL) cholesterol and triglycerides, and increases in high-density lipoprotein (HDL) cholesterol 2, 6.
- The improvement in lipid profiles is thought to be a result of the weight loss and improved insulin sensitivity associated with SGLT2 inhibitor therapy 2.
Cardiovascular Benefits
- SGLT2 inhibitors have been shown to reduce the risk of cardiovascular events, including myocardial infarction, stroke, and cardiovascular death, in patients with type 2 diabetes 3, 4, 5.
- The cardiovascular benefits of SGLT2 inhibitors are thought to be related to their ability to improve hemodynamic parameters, including blood pressure and lipid profiles, as well as their anti-inflammatory and anti-oxidant effects 2.