MISSISSAUGA, ON, Nov. 17, 2011 /CNW/ - Bristol-Myers Squibb Canada and
AstraZeneca Canada today announced results from a pre-specified
meta-analysis of cardiovascular safety data from 14 phase 2b/3 trials
in adult patients with type 2 diabetes that showed no increased risk of
cardiovascular (CV) events associated with the investigational compound
dapagliflozin relative to all comparators pooled in the clinical
program. Dapagliflozin is a novel drug in a new class under evaluation
for the treatment of type 2 diabetes mellitus (T2DM). The
meta-analysis, presented yesterday at the American Heart Association
(AHA) Scientific Sessions in Orlando, FL, was conducted in accordance
with the U.S. Food and Drug Administration (FDA) guidelines for the
assessment of CV safety in new anti-diabetic treatments.
Cardiovascular disease is the leading cause of death in type 2 diabetes
patients.1 Diabetes patients are at acute (two- to four-fold) increase risk for
"Diabetes is a major risk factor for cardiovascular disease and these
preliminary results are reassuring because they show no increase in
heart disease. This new class of medications for the treatment of type
2 diabetes is very promising as it significantly lowers glucose and is
associated with weight loss," said Dr. Vincent Woo, Professor of
Medicine, University of Manitoba, Endocrinologist.
The meta-analysis included 6,228 patients with type 2 diabetes,
including 4,287 patients treated with dapagliflozin (2.5 mg, 5 mg, 10
mg doses) with or without add-on/combination anti-diabetes medication
and 1,941 patients in the control group, treated with a placebo or an
active comparator with or without add-on/combination anti-diabetes
The findings of the meta-analysis indicated that dapagliflozin is not
associated with an increase in cardiovascular disease risk, and are
consistent with a potential reduction in cardiovascular disease risk.3 The primary end point was a composite of time to first event of CV
death, myocardial infarction (MI), stroke, and hospitalization for
About the Study
A pre-specified meta-analysis was conducted using data from 14 phase 2/3
studies (n=6228) to assess the cardiovascular disease safety of all
dapagliflozin doses (2.5 to >10mg/d) pooled (n=4287), relative to all
comparators (active or placebo) pooled (n=1941). Cardiovascular disease
events were systematically identified from investigator reports of
adverse events and adjudicated by an independent committee.
Adjudication was blinded to treatment allocation and conducted
prospectively for the majority of trials3. The primary end point was a composite endpoint of time to first event
of cardiovascular disease death, myocardial infarction (MI), stroke, or
hospitalization for unstable angina. The secondary end point included
measurements of the primary end point, in addition to unplanned
coronary revascularization, and hospitalization for heart failure.
Baseline characteristics were balanced between groups: mean age=56
years, body mass index=31.5 kg/m2, and T2DM duration=six years. Characteristics mirrored cardiovascular
disease risk in the general T2DM population and included hypertension
(62%), dyslipidemia (49%), smoking history (40%), and cardiovascular
disease history (19%).3
A total of 78 primary end point events were confirmed with a stratified
event rate (subjects with events/1000 subject years) of 11.3 for
dapagliflozin vs. 16.6 for comparators. The estimated hazard ratio (HR)
using a Cox proportional hazards method was 0.674 (98% CI: 0.385,
1.178; 95% CI: 0.421, 1.078). Analyses of the secondary end point (HR:
0.632; 95% CI: 0.416, 0.959) and of a composite cardiovascular death,
MI, and stroke end point (HR: 0.596; 95% CI: 0.357, 0.996) were
consistent with primary results. Analyses by dose (dapagliflozin 2.5, 5
and 10 mg) were comparable to overall results. Review of data from the
four month safety update confirmed the conclusions from the initial
pre-specified analysis. The results suggest that dapagliflozin is not
associated with an increase in cardiovascular disease risk, and are
consistent with a potential reduction in cardiovascular disease risk.3
Diabetes Trends in Canada
Type 2 diabetes is a growing epidemic and today, more than nine million
Canadians live with diabetes or prediabetes.4 Type 2 diabetes is a chronic, progressive disease characterized by
insulin resistance and/or dysfunction of beta cells in the pancreas,
which decreases insulin sensitivity and secretion, leading to elevated
glucose levels.6 Over time, this sustained hyperglycemia contributes to worsening
insulin resistance and further beta cell dysfunction.5
New class of treatment for type 2 diabetes
The kidney plays an important role in glucose balance, normally
filtering ~180g of glucose each day, with virtually all glucose being
reabsorbed back into circulation.8 SGLT2 is the major sodium-glucose cotransporter in the kidney and is an
insulin-independent pathway for the reabsorption of glucose back into
the blood. 5,8
Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2)
inhibitor currently under evaluation for the treatment of type 2
diabetes mellitus. Dapagliflozin is currently under review by Health
Canada. If approved, dapagliflozin will be the first SGLT2 inhibitor
in its class. Studies have shown that dapagliflozin promotes urinary
glucose excretion, leading to osmotic diuresis, caloric loss and weight
To date, treatments for type 2 diabetes have focused primarily on
insulin-dependent mechanisms.5 An approach that acts independently of insulin could provide an
additional option for adults with type 2 diabetes.9,10
Bristol-Myers Squibb and AstraZeneca Collaboration
Bristol-Myers Squibb and AstraZeneca entered into a collaboration in
January 2007 to enable the companies to research, develop and
commercialize two investigational drugs for type 2 diabetes -
saxagliptin and dapagliflozin. The Bristol-Myers Squibb/AstraZeneca
diabetes collaboration is dedicated to global patient care, improving
patient outcomes and creating a new vision for the treatment of type 2
diabetes. The companies' collaboration in this therapeutic area is
driven by their joint commitment to global patient care and improving
patient outcomes, and is further strengthened by their deep collective
experience in cardiovascular disease.
About Bristol-Myers Squibb
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of
Bristol-Myers Squibb Company, a global pharmaceutical and related
health care products company whose mission is to extend and enhance
human life. Bristol-Myers Squibb Canada is a leading provider of
medicines to fight cancer, cardiovascular and metabolic disorders,
infectious diseases (including HIV/AIDS), nervous system diseases and
serious mental illness. Bristol-Myers Squibb Company is listed on the
New York Stock Exchange under the BMY symbol (NYSE: BMY). Bristol-Myers
Squibb Canada's operations are headquartered in Montréal, Québec. For
more information about Bristol-Myers Squibb Canada, visit www.bmscanada.ca.
AstraZeneca is committed to the research, development and manufacturing
of valuable prescription medicines. We have an extensive product
portfolio spanning six therapeutic areas: gastrointestinal,
cardiovascular, infection, neuroscience, oncology and respiratory.
AstraZeneca's Canadian headquarters are located in Mississauga,
Ontario, and a state-of-the art drug discovery centre is based in
Montreal, Quebec. For more information, please visit the company's
website at www.AstraZeneca.ca.
Frank Lavernia, Improving Glycemic Control and Cardiometabolic Risk Through Integrated
Treatment Plans. The Journal of Osteopathic Association. July 1, 2010 vol. 110 no. 7 suppl 7 eS13-eS19.
Frank B. Hu, Meir J. Stampfer, et al. Elevated Risk of Cardiovascular Disease Prior to Clinical
Diagnosis of Type 2 Diabetes. Presented in Diabetes Care July 2002 vol. 25 no. 7 1129-1134.
Langkilde AM, Sugg J, Johannson P, Ying L, List J, Parikh S. A
Meta-Analysis of Cardiovascular Outcomes in Clinical Trials of
Dapagliflozin, Presented at American Heart Association Scientific Sessions 2011.
The Prevalence and Costs of Diabetes. Canadian Diabetes Association | Home. Web. 27 Oct. 2011. http://www.diabetes.ca/diabetes-and-you/what/prevalence/.
Washburn WN. Development of the renal glucose reabsorption inhibitors: a
new mechanism for the pharmacotherapy of diabetes mellitus type 2. J Med Chem. 2009; 52(7):1785-1794.
Srinivasan BT, Jarvis J, Khunti K, Davies MJ. Recent advances in the
management of type 2 diabetes mellitus: a review. Postgrad Med J. 2008;84(996):524-531.
Woo V, Langkilde AM, Sugg, Parikh. Dapagliflozin, a novel
antihyperglycemic agent that promotes urinary glucose excretion,
reduces systolic blood pressure in patients with type 2 diabetes
mellitus. Presented at American Heart Association Scientific Sessions 2011.
Rajesh R, Naren P, Vidyasagar S, Unnikrishnan, Pandey S, Varghese M,
Gang S. Sodium glucose co transporter 2 (SGLT2) inhibitors: a new sword
for the treatment of type 2 diabetes mellitus. Int J Pharm Sci Res. 2010;1(2):139-147.
Bailey C, Gross J, Pieters A et al. Effect of dapagliflozin in patients
with type 2 diabetes who have inadequate glycaemic control with
metformin: a randomised, double-blind, placebo-controlled trial. Lancet 2010;375(9733):2223-33.
Wilson, Carol. Diabetes: Dapagliflozin: an insulin-independent,
therapeutic option for type 2 diabetes mellitus. Nature Reviews Endocrinology 6, 531 (October 2010).
SOURCE AstraZeneca Canada Inc.
For further information:
Jane Lee Cheung, Fleishman-Hillard Canada, 416-645-8175, firstname.lastname@example.org
Daniela Cohen, AstraZeneca Canada, 905-615-6827, email@example.com