Dapagliflozin Reduces Adverse Renal and Cardiovascular Events in Patients With Chronic Kidney Disease

Formulary Management of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists

“…If BMI is 30 kg/m 2 or greater or is 27 kg/m 2 with at least 1 comorbidity, drug therapy can include semaglutide, orlistat, liraglutide, and the combination of naltrexone and bupropion� 13 HF is a condition characterized by structural or functional impairment of ventricular filling or ejection of blood, resulting in the heart's inability to maintain the metabolic demands of tissues and organs� 14 Common symptoms of HF include dyspnea, fatigue, and edema� It is estimated that 750,000 people in Canada are living with HF� 15 The goal of treatment is to reduce symptoms and slow the decline of heart function by reducing, stopping, or reversing the progression of the underlying cause� Pharmacological treatment of HF with reduced ejection fraction includes angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, sacubitril-valsartan, ivabradine, and SGLT2 inhibitors� 16,17 CKD is defined as abnormalities of kidney structure or function, which have been present for more than 3 months with implications for health� 18 CKD is characterized based on cause, glomerular filtration rate (GFR), and albuminuria category� CKD is characterized by gradual reduction in kidney function and is estimated to affect approximately 10% of adults living in Canada� 19 Decreased kidney function results in excess build up of fluid, electrolytes, and waste in the body. This leads to reduced quality of life and may result in kidney failure and death� 20,21 Treatment aims to reduce the risk of progression of CKD to kidney failure� 22 Pharmacological therapy for CKD may include ACEis, ARBs, and statins� 23,24 More recently, SGLT2 inhibitors have also demonstrated benefits on renal outcomes in CKD. 25 In 2018 and 2019, SGLT2 inhibitors were among the top 10 drug classes with the largest contribution to growth in public drug program spending in Canada� 26 In 2019, SGLT2 inhibitors contributed to an increase of $61�5 million in total public program spending, 13�2% of the total program spending growth, and 40% of the annual growth rate.…”

Dapagliflozin

“…Lifestyle modification and control of hypertension in patients with proteinuria are key components of treatment to delay progression� 4 Lifestyle modifications can include restrictions on protein and sodium intake (alterations to phosphate and potassium may also be required), being adequately physically active, attaining a healthy body weight, and not smoking� 2 Antihypertensive therapy commonly consists of ACE inhibitors or ARBs� 2 Additional treatments are recommended for patients with comorbid T2DM to delay CKD progression and reduce CV risk� 2 In these patients, glycemic control is considered part of a multifaceted approach that may also include treatment with statins and/or antiplatelet therapies. 2 Additional treatments may be used to address complications (e.g., anemia, acidosis, metabolic bone disease), as well as fluid and electrolyte abnormalities, 2 especially as patients progress to kidney failure� SGLT2 inhibitors were initially developed for patients with T2DM and aimed at treating hyperglycemia; however, their beneficial effects on renal and CV outcomes in these patients have since led to the investigation of this class of drugs on cardiorenal outcomes in patients with CVD and CKD� 5 Of currently available SGLT2 inhibitors believed to have renal benefit, dapagliflozin is indicated for patients with or without T2DM, 1 . In contrast, canagliflozin is indicated only for patients with T2DM.…”

“…Treatment for CKD aims to prevent or delay progression and to address complications resulting from reduced kidney function� 2 Treatment also involves managing the underlying cause of CKD, for example obesity, type 2 diabetes mellitus (T2DM), and cardiac disorders� 4 Lifestyle modification and control of hypertension in patients with proteinuria are key components of treatment to delay progression� 2,4 Antihypertensive therapy commonly consists of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)� 2 Additional treatments are recommended for patients with comorbid T2DM to delay CKD progression and reduce cardiovascular (CV) risk, for example, statins and/or antiplatelet therapies� 2 Additional treatments may be used to address complications (e�g�, anemia, acidosis, metabolic bone disease), as well as fluid and electrolyte abnormalities, 2 especially as patients progress to ESKD� Sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially developed to treat hyperglycemia in patients with T2DM; however, their beneficial effects on renal and CV outcomes have since led to the investigation of this class of drugs on cardiorenal outcomes in patients with CV disease (CVD) and CKD� 5 Of the currently available SGLT2 inhibitors believed to have renal benefit, dapagliflozin is indicated for patients with or without T2DM, 1 . In contrast, canagliflozin is indicated only for patients with T2DM.…”