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Renal and cardiovascular effects of SGLT2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease


Chronic kidney disease ( CKD ) risk is elevated in patients with type 2 diabetes mellitus ( T2DM ).
Disease management in these patients has been generally focused on glycemic control and controlling other renal and cardiac risk factors as, historically, few protective therapies have been available.

The CREDENCE ( Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation ) trial of Canagliflozin ( Invokana ) was the first study to demonstrate renal protection with a SGLT2 ( sodium glucose co-transporter 2 ) inhibitor in patients with T2DM and chronic kidney disease, and these results could have important implications for clinical practice.

In CREDENCE, participants with type 2 diabetes mellitus and estimated glomerular filtration rate 30 - less than 90 mL/min/1.73 m2 and urinary albumin-creatinine ratio more than 300-5,000 mg/g who were treated with an ACE ( angiotensin-converting enzyme ) inhibitor or angiotensin receptor blocker for greater than or equal to 4 weeks prior to randomization at either the maximum labeled or tolerated dose were randomized to receive either Canagliflozin 100 mg or placebo.
Canagliflozin significantly reduced the risk of the primary composite outcome of doubling of serum creatinine, end-stage kidney disease, or renal or cardiovascular death compared with placebo ( hazard ratio, HR=0.70, 95% CI 0.59-0.82; p = 0.00001 ).
Canagliflozin also reduced the risk of secondary renal and cardiovascular outcomes.

The safety profile of Canagliflozin in CREDENCE was generally similar to previous studies of Canagliflozin.
No imbalances were observed between Canagliflozin and placebo in the risk of amputation or fracture in the CREDENCE population.

The positive renal and cardiovascular effects of Canagliflozin observed in the CREDENCE trial could have a substantial impact on improving outcomes for patients with type 2 diabetes mellitus and chronic kidney disease. ( Xagena )

Weir MR et al, Am J Nephrol 2020;51: 276-288

XagenaMedicine_2020



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