From the Guidelines
SGLT2 inhibitors are not primarily used for managing dyslipidemia in type 2 diabetes patients, but they do offer modest beneficial effects on lipid profiles as a secondary benefit. According to the most recent study 1, medications like empagliflozin (Jardiance), canagliflozin (Invokana), and dapagliflozin (Farxiga) typically increase HDL cholesterol by 1-3% and can reduce triglycerides by 5-10%. However, they may slightly increase LDL cholesterol by 2-4%. These effects occur at standard dosing (empagliflozin 10-25mg daily, canagliflozin 100-300mg daily, dapagliflozin 5-10mg daily) while patients take them for glycemic control.
The lipid effects develop within weeks of starting therapy and persist during treatment. SGLT2 inhibitors work by preventing glucose reabsorption in the kidneys, leading to increased urinary glucose excretion. This mechanism reduces blood glucose levels and promotes weight loss, which likely contributes to their modest lipid benefits. Some key points to consider:
- The primary use of SGLT2 inhibitors is to reduce cardiovascular disease and heart failure outcomes in people with diabetes, as stated in 1 and 1.
- For patients specifically requiring dyslipidemia management, statins remain the first-line therapy, with SGLT2 inhibitors serving as complementary agents that provide cardiovascular benefits through multiple pathways beyond lipid effects.
- The benefits of SGLT2 inhibitors on heart failure outcomes have been demonstrated in several trials, including the DAPA-HF and EMPEROR-Reduced trials, as mentioned in 1.
- The American College of Cardiology has recognized the importance of SGLT2 inhibitors in reducing cardiovascular risk in patients with type 2 diabetes and atherosclerotic cardiovascular disease, as stated in 1.
Overall, while SGLT2 inhibitors are not primarily used for managing dyslipidemia, they do offer modest benefits on lipid profiles and provide significant cardiovascular benefits, making them a valuable addition to the treatment regimen for patients with type 2 diabetes.
From the Research
Role of SGLT2 Inhibitors in Managing Dyslipidemia
- SGLT2 inhibitors have been shown to have a beneficial effect on cardiovascular risk factors, including dyslipidemia, in patients with type 2 diabetes 2.
- A real-world retrospective observational study found that SGLT2 inhibitors, such as dapagliflozin and empagliflozin, improved plasma atherogenic biomarkers, including the atherogenic index of plasma (AIP), triglyceride to high density lipoprotein (TG-to-HDL-C) ratio, and the triglyceride glucose (TyG) index, in patients with type 2 diabetes 2.
- The study found that SGLT2i treatment did not alter the lipid profile except for serum triglyceride (TG) levels, which were significantly reduced after 6 months of SGLT2i therapy 2.
- Both empagliflozin and dapagliflozin caused significant decreases in AIP and TyG index, indicating a reduction in atherosclerotic cardiovascular risk, with or without statin treatment regardless of lipid parameters 2.
Mechanism of Action
- SGLT2 inhibitors work by inhibiting the reabsorption of filtered glucose in the kidney, increasing urinary glucose excretion and reducing blood glucose levels 3.
- The mechanism of action of SGLT2 inhibitors is independent of pancreatic β cell function and modulation of insulin sensitivity 3.
Clinical Implications
- SGLT2 inhibitors, such as empagliflozin and canagliflozin, have been shown to reduce the risk of composite cardiovascular events in high-risk individuals with type 2 diabetes 4.
- Empagliflozin has also been shown to reduce cardiovascular deaths and improve renal outcomes 4.
- SGLT2 inhibitors should be considered in people with established cardiovascular disease, usually in combination with other glucose-lowering medications, when satisfactory glycaemic control has not been achieved 4.