Dapagliflozin, widely recognized as an SGLT2 inhibitor under the brand name Farxiga, is primarily used to treat type 2 diabetes mellitus (T2DM) and heart failure. As a glucose-lowering agent, it works by preventing glucose reabsorption in the kidneys, promoting urinary glucose excretion, and subsequently improving glycemic control. This mechanism also confers secondary benefits, including weight reduction and blood pressure control, making it an integral part of managing cardiometabolic diseases.
However, new research is now expanding dapagliflozin’s potential, particularly in treating transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). ATTR-CM is a rare but often fatal form of amyloid deposition in the heart, characterized by the misfolding of the transthyretin (TTR) protein. This misfolded protein aggregates into amyloid fibrils that stiffen the heart muscle, leading to heart failure. ATTR-CM is underdiagnosed, especially in patients with heart failure with preserved ejection fraction (HFpEF), where up to 15% of cases are attributed to undetected amyloid deposition.
New Evidence from ESC Congress 2024
At the ESC Congress 2024, AstraZeneca unveiled significant findings about dapagliflozin’s impact on ATTR-CM. The newly released CARDIO-TTRansform cardiac magnetic resonance (CMR) sub-analysis is exploring how dapagliflozin may reduce amyloid burden in the heart. Early evidence shows promising results, suggesting that dapagliflozin might influence amyloid deposition while improving heart failure outcomes. This is especially relevant as ATTR-CM progresses slowly but leads to severe heart dysfunction if untreated. Addressing it early could significantly alter disease progression.
The Mechanism and Broader Impact of Dapagliflozin
Dapagliflozin’s mechanism as an SGLT2 inhibitor directly contributes to its cardiovascular benefits. Its diuretic effect reduces the workload on the heart, particularly beneficial in heart failure. For ATTR-CM patients, this is crucial as amyloid deposits stiffen the heart, reducing its ability to pump efficiently. In HFpEF, where heart stiffness impairs relaxation and filling, dapagliflozin’s dual role in improving heart function and potentially reducing amyloid deposition could become a cornerstone in treatment
Importance of Early Detection
The evidence emphasizes the need for early detection of ATTR-CM in heart failure patients. Diagnostic advances, including cardiac magnetic resonance imaging (CMR) and genetic testing, now offer improved accuracy in diagnosing ATTR-CM, leading to earlier treatment. When combined with existing therapies like TTR stabilizers (e.g., tafamidis), dapagliflozin could provide a comprehensive approach to managing both heart failure and amyloid deposition.
Expanded Indications and Future Prospects
As more studies reveal dapagliflozin’s efficacy in ATTR-CM, its indications may expand to include patients with this rare cardiomyopathy. The drug could potentially reduce amyloid burden, slow disease progression, and improve heart function, offering new hope to a patient population with limited treatment options. The combination of its glucose-lowering, cardioprotective, and possible amyloid-modulating effects makes dapagliflozin a powerful agent in cardiometabolic disease management.
Key Takeaways:
- Dapagliflozin has proven benefits in treating T2DM, heart failure, and now, potentially, ATTR-CM.
- ATTR-CM is underdiagnosed, especially in HFpEF patients, but early detection can significantly improve outcomes.
- Emerging research, including the CARDIO-TTRansform study, suggests dapagliflozin may reduce amyloid deposition in the heart.
- The drug’s dual benefits for heart failure and amyloid-related diseases could lead to expanded therapeutic indications in the near future
