Keterangan
Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor that has shown promise in the management of Chronic Kidney Disease (CKD) in patients with type 2 diabetes. Dapagliflozin has demonstrated efficacy in reducing the progression of CKD in individuals with type 2 diabetes by inhibiting the reabsorption of glucose and sodium in the proximal renal tubules. Clinical trials have indicated that dapagliflozin reduces albuminuria, a key marker of kidney damage, thereby potentially slowing the decline in renal function. The use of dapagliflozin has been associated with improvements in glomerular filtration rate (GFR), suggesting a positive impact on overall kidney function. Dapagliflozin's mechanism of action involves promoting glycosuria and natriuresis, leading to a reduction in intraglomerular pressure and ultimately protecting the kidneys. Studies have highlighted the cardiovascular benefits of dapagliflozin in CKD patients, including a reduction in major adverse cardiovascular events and heart failure hospitalizations. Dapagliflozin's renal protective effects extend beyond glycemic control, making it a valuable therapeutic option for patients with both diabetes and CKD. The safety profile of dapagliflozin in CKD patients appears favorable, with few adverse effects reported in clinical trials. Dapagliflozin's impact on renal outcomes has prompted its inclusion in treatment guidelines for individuals with type 2 diabetes and CKD.
Ringkasan
- The speaker discusses SGLT2 inhibitors, a relatively new class of anti-diabetic medications introduced around 2018-2019, highlighting their significant impact on managing diabetic kidney disease (DKD) and chronic kidney disease (CKD). They emphasize the breakthrough nature of these drugs, especially considering the limited concrete options available for handling these conditions in previous decades.
- SGLT2 inhibitors, like dapagliflozin, demonstrate benefits in preventing the progression of diabetic end-organ damage, including heart and kidney complications. The mechanism involves reducing glucose reabsorption in the kidneys by inhibiting SGLT2 receptors, leading to glucose excretion in urine, blood pressure reduction, and potential weight loss. While starting SGLT2 inhibitors can cause a temporary drop in GFR (glomerular filtration rate), this is generally reversible.
- Clinical trials from 1990 to 2022 reveal a shift, with early trials focusing on ACE inhibitors and ARBs, while later studies highlight the efficacy of SGLT2 inhibitors such as dapagliflozin and canagliflozin in both diabetic and non-diabetic kidney disease. The speaker stresses the severity of CKD and the limited availability of drugs to effectively prevent its progression, further underscoring the importance of SGLT2 inhibitors.
- SGLT2 inhibitors affect uric acid levels by promoting its secretion in the urine in exchange for glucose reabsorption, which helps to reduce hyperuricemia, a known contributor to CKD progression. The speaker details the tubuloglomerular feedback mechanism, explaining how SGLT2 inhibitors help restore normal sodium delivery to the distal tubule, preventing hyperfiltration and damage to the glomerulus.
- Adverse effects of SGLT2 inhibitors include euglycemic ketoacidosis (more common in type 1 diabetes), genital mycotic infections (more common in females), and potential volume depletion. The speaker also addresses concerns about bone fractures and cancer, clarifying that newer drugs like empagliflozin and dapagliflozin do not show increased amputation risk, unlike canagliflozin. Kidney-specific side effects, such as urosepsis and pyelonephritis, are also mentioned due to increased glucose secretion.
- Key trials like EMPA-REG OUTCOME, CANVAS, and CREDENCE demonstrate that SGLT2 inhibitors reduce dialysis requirements, kidney transplant needs, and renal death in CKD patients. Forest plotting analysis further confirms the advantage of these drugs in improving renal outcomes, with significant statistical significance in these studies.
- The DAPA-CKD trial, a randomized, double-blind, placebo-controlled study, supports the use of dapagliflozin in both diabetic and non-diabetic CKD patients. The study design includes participants with lower EGFR levels and stable ACE inhibitors or ARBs. The trial's primary endpoint included a decline in GFR, ESRD onset, and death from renal or cardiovascular causes, showing overwhelmingly positive results for dapagliflozin.
- DAPA-CKD trial showed that dapagliflozin reduces the risk of kidney failure, cardiovascular death, and hospitalization for heart failure. The speaker referenced empa kidney, which also showed similar benefits and had patients with even lower GFR. They reiterated that HT inhibitors show significant cardiac and renal benefits in both diabetic and non-diabetic patients.
Contoh Sertifikat
Tentang Pembicara
Dr Satyanarayana Garre
MBBS, MD, DNB( Nephrology) Apollo hospitals Hyderabad
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