Exploratory analysis from FARXIGA DAPA-HF
Phase III trial will provide insights on the onset of type 2
diabetes in heart failure patients
Sub-analyses from the DECLARE Phase III
trial to highlight FARXIGA’s effect on fast renal decline
AstraZeneca will present new data from the landmark Phase III
DAPA-HF and DECLARE-TIMI 58 trials at the upcoming 80th American
Diabetes Association (ADA) Virtual Scientific Sessions, June 12 –
16 2020. The data are among 23 accepted abstracts, including four
oral presentations, covering trials that showcase the depth and
breadth of potential cardio, renal and metabolic benefits for
patients across AstraZeneca’s portfolio.
Highlights include:
- An oral presentation of data from the DAPA-HF trial showing the
effect of FARXIGA® (dapagliflozin) on the incidence of new onset of
type 2 diabetes (T2D) in patients with heart failure and reduced
ejection fraction (HFrEF) (Abstract #271-OR)1
- New sub analyses from the DECLARE-TIMI 58 trial, presented
orally, providing insights on FARXIGA’s effect on fast kidney
function decline in T2D patients with established or increased risk
for cardiovascular disease (Abstract #303-OR)2
- An analysis of the DAPA-HF trial examining if background T2D
therapy impacts the benefits of FARXIGA in heart failure (HF)
(Abstract #1112-P)3
- A new analysis of the global observational DISCOVER real world
evidence study, presented orally, reporting health-related quality
of life factors in patients with T2D initiating a second-line
glucose-lowering therapy (Abstract #40-OR)4
- An oral presentation of new Phase II data on investigational
cotadutide, a dual receptor agonist with balanced GLP-1 and
glucagon activity, showing positive effect on blood glucose levels
and changes in liver fat and glycogen stores in patients with T2D
(Abstract #354-OR)5
- BRILINTA® (ticagrelor) data on duration of T2D, baseline HbA1c
levels as well as the impact of blood sugar-lowering background
therapies on outcomes in T2D patients with coronary artery disease
(THEMIS diabetes subgroup) (Abstract #403-P)6
Ruud Dobber, Executive Vice President, BioPharmaceuticals
Business Unit, said: “An overwhelming majority of people with type
2 diabetes also have at least one other cardiovascular, renal or
metabolic disease. The breadth and depth of data we are presenting
at ADA 2020 demonstrates our commitment to developing treatment
options for patients living with diabetes that go beyond glycemic
control to also protect the heart, liver and kidneys.”
In addition to its robust clinical data, AstraZeneca will also
present results from a global survey of more than 1,600 physicians
in 18 countries examining primary care approaches and clinical
inertia in the treatment of patients with T2D.
Key abstracts and other notable abstracts to be presented at
ADA:
Lead author
Abstract title
Presentation details
Cotadutide
Robertson, D.
Cotadutide (MEDI0382), a Dual Receptor
Agonist With Glucagon-like Peptide-1 and Glucagon Activity,
Modulates Hepatic Glycogen and Fat Content
Oral Presentation Monday, June 15 5:30 –
5:45 #354-OR
Robertson, D.
Cotadutide (MEDI0382), A Dual Receptor
Agonist With Glucagon-like Peptide-1 And Glucagon Activity, Is
Well-tolerated (<600 μG) With Robust Effects On Blood Glucose In
Patients With T2DM
Poster Presentation Saturday, June 13
10:00 – 11:00 #951-P
Laker, R.C.
Cotadutide, a GLP-1/Gcg Receptor
Co-agonist Improves Insulin Sensitivity and Restores Normal Insulin
Secretory Capacity in DIO Mice
Poster Presentation Saturday, June 13
10:00 – 11:00 #1800-P
FARXIGA
Inzucchi, SE.
Effect of Dapagliflozin on the Incidence Of
Diabetes: A Prespecified Exploratory Analysis From DAPA-HF
Oral Presentation Monday, June 15 8:00 –
8:15 #271-OR
Raz, I.
Effect of Dapagliflozin on Risk for Fast
Decline in eGFR: Analyses from the DECLARE-TIMI 58 Trial
Oral Presentation Monday, June 15 2:30 –
2:45 #303-OR
Cahn, A.
Cardiorenal Outcomes with Dapagliflozin by
Baseline Glucose Lowering Agents Analyses from DECLARE-TIMI 58
Poster Presentation Saturday, June 13
10:00 – 11:00 #1101-P
Ang, L.
Dapagliflozin and Measures of
Cardiovascular Autonomic Function in Patients with Type 2
Diabetes
Poster Presentation Saturday, June 13
10:00 – 11:00 #554-P
Ono, S.
Effects of Long-term Dapagliflozin
Treatment on Hemorheology (D-PATH Study)
Poster Presentation Saturday, June 13
10:00 – 11:00 #1106-P
Docherty, KF.
Does Background T2D Therapy Modify the
Benefits of Dapagliflozin in Heart Failure? Analysis of the DAPA-HF
Trial
Poster Presentation Saturday, June 13
10:00 – 11:00 #1112-P
Sato, D.
Dapagliflozin Suppresses Adipose Fatty
Acid Accumulation in Rats Fed on High-Fat Diet but not on Normal
Chow
Poster Presentation Saturday, June 13
10:00 – 11:00 #1946-P
Faerch, K.
Changes in Plasma Levels of Liver Enzymes
in Response to Dapagliflozin, Metformin or Exercise in People with
Prediabetes: The PRE-D Trial
Poster Presentation Saturday, June 13
10:00 – 11:00 #845-P
Clemmensen, KKB.
Effects Of Dapagliflozin, Metformin Or
Exercise On Plasma Glucagon Concentrations in Individuals With
Prediabetes: The PRE-D Trial
Poster Presentation Saturday, June 13
10:00 – 11:00 #844-P
Kabir, M.
Dapagliflozin Promotes Adipose Beiging and
Lipolysis and Reduces Adipocyte Size in the Obese Prediabetic
Dog
Poster Presentation Saturday, June 13
10:00 – 11:00 #1711-P
Brunton, S.
Approaches to and Inertia in
Cardiovascular and Renal Risk Management of Type 2 Diabetes
Patients in Primary Care: Global Quantitative Survey Results
Poster Presentation Saturday, June 13
10:00 – 11:00 #1188-P
DISCOVER
Bonnet, F.
HbA1c < 7.0% 6 Months after Initiation
of Second-Line Therapy in Patients with Uncontrolled Type 2
Diabetes is Associated with Good Glycemic Control at 3 Years: The
DISCOVER Study
Poster Presentation Saturday, June 13
10:00 – 11:00 #1598-P
Nicolucci, A.
Quality of Life in People with Type 2
Diabetes Following Initiation of Second-Line Therapy: DISCOVER
Oral Presentation Friday, June 12 6:00 –
6:15 #40-OR
Khunti, K.
Effects of Second-Line Metformin
Combination Therapies on Weight, HbA1c, and Risk of Hypoglycemia
over 3 Years: The DISCOVER Study
Poster Presentation Saturday, June 13
10:00 – 11:00 #1590-P
BYDUREON
Clegg, LE.
Once-Weekly Exenatide Effects on eGFR
Slope and UACR as a Function of Baseline UACR: An EXSCEL Trial Post
Hoc Analysis
Poster Presentation Saturday, June 13
10:00 – 11:00 #958-P
BRILINTA
Leiter, LA.
Impact of Diabetes-Related Factors And
Background Antihyperglycemic Therapy On The Efficacy And Safety Of
Ticagrelor Added To Aspirin: Insights From The THEMIS Trial
Poster Presentation Saturday, June 13
10:00 – 11:00 #403-P
Early Research &
Development
Mather, K.
A Direct AMPK Activator Reduces Liver
Steatosis in a Mouse Model of NASH
Poster Presentation Saturday, June 13
10:00 – 11:00 #1820-P
Cheng, W.
Synergetic and Distinct Roles in the
Control of Food Intake and Energy Balance for Subpopulations of NTS
Neurons
Late-Breaking Poster Presentation
Saturday, June 13 10:00 – 11:00 #196-LB
Gray, SM.
Discrepancy between Single-Cell RNA
Sequencing and Protein Expression Assessments of GLP-1Rr
Heterogeneity in Beta Cells
Poster Presentation Saturday, June 13
10:00 – 11:00 #2113-P
Gray, SM.
Quantification of GLP-1R Trafficking in
Primary Beta Cells in Response to Different Ligands
Poster Presentation Saturday, June 13
10:00 – 11:00 #2114-P
INDICATIONS AND LIMITATIONS OF USE for FARXIGA®
(dapagliflozin)
FARXIGA is indicated:
- as an adjunct to diet and exercise to improve glycemic control
in adults with type 2 diabetes mellitus
- to reduce the risk of hospitalization for heart failure in
adults with type 2 diabetes mellitus and established cardiovascular
(CV) disease or multiple CV risk factors
- to reduce the risk of cardiovascular death and hospitalization
for heart failure in adults with heart failure (NYHA class II-IV)
with reduced ejection fraction
FARXIGA is not recommended for patients with type 1 diabetes
mellitus or for the treatment of diabetic ketoacidosis.
IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5
mg and 10 mg tablets
Contraindications
- Prior serious hypersensitivity reaction to FARXIGA
- Patients with severe renal impairment (eGFR <30 mL/min/1.73
m2) being treated for glycemic control without established CV
disease or multiple CV risk factors
- Patients on dialysis
Warnings and Precautions
- Volume Depletion: FARXIGA can cause intravascular volume
depletion which may manifest as symptomatic hypotension or acute
transient changes in creatinine. Acute kidney injury requiring
hospitalization and dialysis has been reported in patients with
type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA.
Patients with impaired renal function (eGFR less than 60
mL/min/1.73 m2), elderly patients, or patients on loop diuretics
may be at increased risk for volume depletion or hypotension.
Before initiating FARXIGA in these patients, assess volume status
and renal function. After initiating therapy, monitor for signs and
symptoms of hypotension and renal function
- Ketoacidosis in Diabetes Mellitus 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
- 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 with diabetes mellitus 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
Adverse Reactions
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
DOSING
- To improve glycemic control in patients with T2D, the
recommended starting dose of FARXIGA is 5 mg orally once daily,
taken in the morning. In patients tolerating FARXIGA 5 mg once
daily who require additional glycemic control, the dose can be
increased to 10 mg once daily
- To reduce the risk of hospitalization for heart failure in
patients with T2D and established CV disease or multiple CV risk
factors, the recommended dose of FARXIGA is 10 mg orally once
daily
- To reduce the risk of CV death and hospitalization for heart
failure in patients with HFrEF, the recommended dose of FARXIGA is
10 mg orally once daily
Please see accompanying US Full Prescribing Information and
Medication Guide for FARXIGA.
INDICATIONS
BRILINTA is indicated to reduce the risk of cardiovascular
death, myocardial infarction (MI), and stroke in patients with
acute coronary syndrome (ACS) or a history of myocardial
infarction. For at least the first 12 months following ACS, it is
superior to clopidogrel. BRILINTA also reduces the risk of stent
thrombosis in patients who have been stented for treatment of
ACS.
BRILINTA is indicated to reduce the risk of a first MI or stroke
in patients with coronary artery disease (CAD) at high risk for
such events. While use is not limited to this setting, the efficacy
of ticagrelor was established in a population with type 2
diabetes.
DOSING
In the management of ACS, initiate BRILINTA treatment with a
180-mg loading dose. Administer 90 mg twice daily during the first
year after an ACS event. After one year administer 60 mg twice
daily.
In patients with CAD but no prior stroke or MI, administer 60 mg
twice daily.
Use BRILINTA with a daily maintenance dose of aspirin of 75-100
mg.
IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-MG
AND 90-MG TABLETS
WARNINGS:
A. BLEEDING RISK
- BRILINTA, like other antiplatelet agents, can cause
significant, sometimes fatal bleeding
- Do not use BRILINTA in patients with active pathological
bleeding or a history of intracranial hemorrhage
- Do not start BRILINTA in patients undergoing urgent coronary
artery bypass graft surgery
- If possible, manage bleeding without discontinuing BRILINTA.
Stopping BRILINTA increases the risk of subsequent cardiovascular
events
B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS
- Maintenance doses of aspirin above 100 mg reduce the
effectiveness of BRILINTA and should be avoided
CONTRAINDICATIONS
- BRILINTA is contraindicated in patients with a history of
intracranial hemorrhage or active pathological bleeding such as
peptic ulcer or intracranial hemorrhage. BRILINTA is also
contraindicated in patients with hypersensitivity (eg, angioedema)
to ticagrelor or any component of the product.
WARNINGS AND PRECAUTIONS
- Dyspnea was reported more frequently with BRILINTA than in
patients treated with control agents. Dyspnea from BRILINTA is
often self-limiting
- Discontinuation of BRILINTA will increase the risk of MI,
stroke, and death. When possible, interrupt therapy with BRILINTA
for 5 days prior to surgery that has a major risk of bleeding. If
BRILINTA must be temporarily discontinued, restart as soon as
possible
- Ticagrelor can cause ventricular pauses. Bradyarrhythmias
including AV block have been reported in the post-marketing
setting. Clinical trials excluded patients at increased risk of
bradyarrhythmias not protected by a pacemaker, and they may be at
increased risk of developing bradyarrhythmias
- Avoid use of BRILINTA in patients with severe hepatic
impairment. Severe hepatic impairment is likely to increase serum
concentration of ticagrelor and there are no studies of BRILINTA in
these patients
- In patients with Heparin Induced Thrombocytopenia (HIT): False
negative results for HIT-related platelet functional tests,
including the heparin-induced platelet aggregation (HIPA) assay,
have been reported with BRILINTA. BRILINTA is not expected to
impact PF4 antibody testing for HIT
ADVERSE REACTIONS
- The most common adverse reactions (>5%) associated with the
use of BRILINTA included bleeding and dyspnea
DRUG INTERACTIONS
- Avoid use with strong CYP3A inhibitors and strong CYP3A
inducers. BRILINTA is metabolized by CYP3A4/5. Strong inhibitors
substantially increase ticagrelor exposure and so increase the risk
of adverse events. Strong inducers substantially reduce ticagrelor
exposure and so decrease the efficacy of ticagrelor
- As with other oral P2Y12 inhibitors, co-administration of
opioid agonists delay and reduce the absorption of ticagrelor.
Consider use of a parenteral anti-platelet in ACS patients
requiring co-administration
- Patients receiving more than 40 mg per day of simvastatin or
lovastatin may be at increased risk of statin-related adverse
events
- Monitor digoxin levels with initiation of, or change in,
BRILINTA therapy
SPECIAL POPULATIONS
- Lactation: Breastfeeding not recommended
Please read full Prescribing Information, including Boxed
WARNINGS, and Medication Guide.
INDICATION AND LIMITATIONS OF USE
BYDUREON BCise is indicated as an adjunct to diet and exercise
to improve glycemic control in adults with type 2 diabetes
mellitus
- Not recommended as first-line therapy for patients inadequately
controlled on diet and exercise
- Not a substitute for insulin. Should not be used to treat type
1 diabetes or diabetic ketoacidosis
- Use with prandial insulin has not been studied
- Do not coadminister with other exenatide-containing
products
- Not studied in patients with a history of pancreatitis.
Consider other antidiabetic therapies in patients with a history of
pancreatitis
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF THYROID C-CELL TUMORS
- Exenatide extended-release causes an increased incidence in
thyroid C-cell tumors at clinically relevant exposures in rats
compared to controls. It is unknown whether BYDUREON BCise causes
thyroid C-cell tumors, including medullary thyroid carcinoma (MTC)
in humans, as the human relevance of exenatide
extended-release-induced rodent thyroid C-cell tumors has not been
determined
- BYDUREON BCise is contraindicated in patients with a
personal or family history of MTC or in patients with Multiple
Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients
regarding the potential risk of MTC with the use of BYDUREON BCise
and inform them of symptoms of thyroid tumors (eg, mass in the
neck, dysphagia, dyspnea, persistent hoarseness). Routine
monitoring of serum calcitonin or using thyroid ultrasound is of
uncertain value for detection of MTC in patients treated with
BYDUREON BCise
CONTRAINDICATIONS
- Personal or family history of MTC, patients with MEN 2
- Prior serious hypersensitivity reactions to exenatide or
product components
- History of drug-induced, immune-mediated thrombocytopenia from
exenatide products
WARNINGS AND PRECAUTIONS
- Acute Pancreatitis including fatal and non-fatal
hemorrhagic or necrotizing pancreatitis has been reported. After
initiation, observe patients carefully for symptoms of
pancreatitis. If suspected, discontinue promptly and do not restart
if confirmed. Consider other antidiabetic therapies in patients
with a history of pancreatitis
- Hypoglycemia Risk of hypoglycemia is increased when
exenatide is coadministered with insulin or insulin secretagogues.
Consider lowering the dose of these agents when coadministered with
BYDUREON BCise
- Acute Kidney Injury May induce nausea and vomiting with
transient hypovolemia and may worsen renal function. Increased
serum creatinine, renal impairment, worsened chronic renal failure,
and acute renal failure, sometimes requiring hemodialysis and
kidney transplantation have been reported. Not recommended in
patients with eGFR <45 mL/min/1.73 m2
- Gastrointestinal Disease Because exenatide is commonly
associated with gastrointestinal adverse reactions, not recommended
in patients with severe gastrointestinal disease (eg,
gastroparesis)
- Immunogenicity Patients may develop antibodies to
exenatide. Patients with higher titer antibodies may have an
attenuated HbA1c response. In clinical trials, attenuated glycemic
response was associated with BYDUREON BCise-treated patients. If
worsening of or failure to achieve adequate glycemic control
occurs, consider alternative antidiabetic therapy
- Hypersensitivity Reports of serious hypersensitivity
reactions (eg, anaphylaxis and angioedema). If this occurs,
patients should discontinue BYDUREON BCise and promptly seek
medical advice
- Drug-induced, immune-mediated thrombocytopenia and
associated bleeding has been reported with exenatide. Serious
bleeding, which may be fatal, has been reported. Discontinue
promptly if suspected and avoid re-exposure to exenatide
- Injection-Site Reactions Serious reactions (eg, abscess,
cellulitis, and necrosis), with or without subcutaneous nodules,
have been reported
- Acute Gallbladder Disease has been reported in GLP-1
receptor agonist trials, including exenatide. If cholelithiasis or
cholecystitis are suspected, gallbladder studies are indicated
ADVERSE REACTIONS
Most common (≥5%) in clinical trials: injection-site nodule
(10.5%), nausea (8.2%).
DRUG INTERACTIONS
- Oral Medications BYDUREON BCise slows gastric emptying
and may reduce the rate of absorption of orally administered
drugs
- Warfarin Increased international normalized ratio (INR)
sometimes associated with bleeding has been reported with
concomitant use of exenatide with warfarin. Monitor INR frequently
until stable upon initiation of BYDUREON BCise
PREGNANCY
Use during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
Please see full Prescribing Information, including Boxed
WARNINGS, for BYDUREON, and BYDUREON BCise.
AstraZeneca in CV, Renal & Metabolism (CVMD)
CV, renal and metabolism together form one of AstraZeneca’s main
therapy areas and a key growth driver for the Company. By following
the science to understand more clearly the underlying links between
the heart, kidneys 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 potentially regenerate organs and
restore function, by continuing to deliver transformative science
that improves treatment practices and CV health for millions of
patients worldwide.
About AstraZeneca
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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