ACC/AHA 2019 Primary Prevention Guideline and AACE/ACE Comprehensive Type 2 Diabetes Management Algorithm also recently updated to incorporate these findings
Today, AstraZeneca confirmed that the American Diabetes Association (ADA) issued critical updates to the Standards of Medical Care in Diabetes (Standards of Care) based on recently published research, including data from the landmark DECLARE-TIMI 58 cardiovascular (CV) outcomes trial (CVOT). Specifically, three sections were updated to incorporate data related to hospitalizations for heart failure (hHF) and progression of chronic kidney disease (CKD) from the DECLARE-TIMI 58 trial. The updates were issued in annotations as the Living Standards of Care. Full details of the Living Standards of Care are available online at Diabetes Care.
DECLARE-TIMI 58 is the largest and longest SGLT-2 inhibitor CVOT studied across a broad range of type 2 diabetes (T2D) patients and the first to include the composite of hHF or CV death as a primary endpoint. The trial included nearly 60% of patients with multiple CV risk factors, making it the largest primary prevention population of the SGLT-2i CVOTs.
Rod Wooten, Senior Vice President, US Cardiovascular and Metabolic Diseases, AstraZeneca said: “Heart failure is the number one cardiac complication in type 2 diabetes, and patients with type 2 diabetes have a two-to-five times greater risk of heart failure along with an increased risk of other cardiovascular complications like heart attack or stroke. Moreover, diabetes is the leading cause of chronic kidney disease, and approximately one out of four adults with diabetes has kidney disease. We are pleased the American Diabetes Association worked quickly to incorporate new data into clinical practice guidance to help empower healthcare professionals to provide evidence-based care and help improve these outcomes for the millions of Americans living with diabetes.”
The update to the 2019 ADA Standards of Medical Care in Diabetes follows the publication of the American College of Cardiology (ACC) and American Heart Association (AHA) Primary Prevention Guideline, and the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) Comprehensive Type 2 Diabetes Management Algorithm, both of which incorporate data from DECLARE-TIMI 58 and reinforce the role of SGLT-2 inhibitors in reducing renal and cardiovascular risk, including heart failure. The ADA, ACC/AHA, and AACE/ACE treatment guidelines include unapproved uses of FARXIGA (dapagliflozin). FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is not indicated to reduce the risk of CV events including HF, renal outcomes or death.
Full results from the DECLARE-TIMI 58 trial were presented at the American Heart Association Scientific Sessions in November 2018. AstraZeneca continues to expand its research program through the Phase III DAPA-HF trial, the first trial to assess the potential CV benefits of an SGLT-2 inhibitor in patients with and without T2D and DAPA-CKD, investigating renal outcomes and cardiovascular mortality in patients with CKD.
Indication and Limitations of Use for FARXIGA® (dapagliflozin) tablets
FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Important Safety Information for FARXIGA® (dapagliflozin) tablets
- Prior serious hypersensitivity reaction to FARXIGA
- Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
Warnings and Precautions
- Hypotension: FARXIGA causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating FARXIGA in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension
- Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
- Acute Kidney Injury and Impairment in Renal Function: FARXIGA causes intravascular volume contraction and renal impairment, with reports of acute kidney injury requiring hospitalization and dialysis. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat.
FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating FARXIGA, evaluate renal function and monitor periodically. FARXIGA is not recommended when the eGFR is <45 mL/min/1.73 m2
- Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections [UTIs] and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
- Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
- Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Rare but serious, life-threatening cases have been reported in patients receiving SGLT2 inhibitors including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA.
- Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
- Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur with FARXIGA. Monitor LDL-C and treat per standard of care
- Bladder cancer: An imbalance in bladder cancers was observed in clinical trials. There were too few cases to determine whether the emergence of these events is related to FARXIGA, and insufficient data to determine whether FARXIGA has an effect on pre-existing bladder tumors. FARXIGA should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
- Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with FARXIGA
In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).
Use in Specific Populations
- Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters.
- Lactation: FARXIGA is not recommended when breastfeeding.
NOTES TO EDITORS
About DECLARE-TIMI 58
DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI 58 is an AstraZeneca-sponsored, randomized, double-blinded, placebo-controlled, multicentre trial designed to evaluate the effect of FARXIGA compared with placebo on CV outcomes in adults with T2D at risk of CV events, including patients with multiple CV risk factors or established CV disease. DECLARE included more than 17,000 patients across 882 sites in 33 countries and was independently run in collaboration with academic investigators from the TIMI study group (Boston, USA) and the Hadassah Hebrew University Medical Center (Jerusalem, Israel).
DECLARE is part of the extensive DapaCare clinical programme for FARXIGA, which will enroll patients in randomised clinical trials including a wide range of mechanistic trials and is supported by a multinational real-world evidence study (CVD-REAL). The DapaCare clinical programme will generate data across a spectrum of people with CV risk factors, established CV disease and varying stages of renal disease, both with and without T2D. DECLARE is paving the way for three Phase III trials: Dapa-HF, DELIVER and Dapa-CKD. FARXIGA is not indicated to reduce the risk of CV events, CV death, or hHF, or the treatment of CKD.
About AstraZeneca in Cardiovascular, Renal & Metabolism (CVMD)
Cardiovascular, renal and metabolic diseases together form one of AstraZeneca’s main therapy areas and platforms for future growth. By following the science to understand more clearly the underlying links between the heart, kidney and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVMD diseases and even regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
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US-28219 Last Updated 3/19