- First type 2 diabetes mellitus (T2DM) treatment to demonstrate cardiovascular (CV) and renal protection in patients with and without a history of CV disease.
CAMBRIDGE, UK: 11.06.19 – Napp today welcomes the results of a new subgroup analysis from the landmark Phase III CREDENCE study. The analysis showed that the antidiabetic treatment canagliflozin significantly reduced the risk of major CV events and kidney failure in T2DM patients with chronic kidney disease (CKD) with and without known CV disease.1 The results were presented at the American Diabetes Association’s 79th Scientific Sessions in San Francisco, USA.
There are an estimated 4.7 million people living with type 2 diabetes in the UK, approximately 40% of whom will go on to develop CKD., CKD worsens the short and long-term prognosis for many common CV diseases and predominantly accounts for the increased mortality observed in T2DM. For people living with CKD and T2DM this equates to a 16 year loss in life expectancy, far higher than for T2DM or CKD on their own.
In the new subgroup analysis of the clinical trial results, researchers specifically examined CV and renal outcomes in a primary prevention group, which included participants with CV risk factors but no history of CV disease (n=2,181; 49.6%) and a secondary prevention group, including patients defined as having a history of coronary, cerebrovascular or peripheral vascular disease (n=2,220; 50.4%).1
The subgroup analysis showed that the CV results observed in the overall study population were consistent across the primary and secondary prevention groups, including all clinical subgroups and across groups defined by renal function. For CV death, heart attack and stroke, there was no evidence of heterogeneity between the primary and secondary prevention groups (p=0.25). Specifically, canagliflozin reduced the risk of the composite of CV death, heart attack and stroke by 32% in the primary prevention group (HR: 0.68; 95% CI: 0.49 to 0.94) and 15% in the secondary prevention group (HR: 0.85; 95% CI: 0.69 to 1.06).1
Furthermore, the renal results observed in the overall study population were consistent across the primary and secondary prevention groups. Specifically, canagliflozin reduced the risk of ESKD by 31% (HR: 0.69; 95% CI: 0.51 to 0.95; P-interaction: 0.89) and 33% (HR: 0.67; 95% CI: 0.47 to 0.96; P-interaction: 0.89) in the primary and secondary prevention groups, respectively.1
“Cardiovascular disease and kidney disease are two serious complications of type 2 diabetes that may shorten life expectancy by several years. This latest analysis of the CREDENCE study demonstrates that for patients with type 2 diabetes and chronic kidney disease, canagliflozin reduces the risk of a cardiovascular event, whether or not patients have already experienced one. This has the potential to help to prevent clinical manifestations of cardiovascular disease – an area of great interest for healthcare professionals managing these patients.” said David Wheeler, Professor of Kidney Medicine at University College London, UK and Honorary Consultant Nephrologist at the Royal Free London NHS Foundation
In addition, CREDENCE found the incidence rates of adverse events and serious adverse events were numerically lower for patients treated with canagliflozin as compared to placebo.6 For the subgroup analysis, safety outcomes were similar in both primary and secondary prevention groups. Of note, there was no difference in fracture risk or incidence of amputations in the primary and secondary prevention groups.1
“The initial results from CREDENCE were an exciting development for clinicians trying to manage type 2 diabetes and diabetic kidney disease. What this new analysis suggests is that CREDENCE has much more to tell us about the important connection between good kidney health and good heart health in type 2 diabetes.” said Andrea Brown, spokesperson for the National Kidney Federation, UK.
“It is estimated that 80% of the £10 billion annual NHS expenditure on type 2 diabetes goes towards managing complications of the disease, including cardiovascular and diabetic kidney disease. It is encouraging to see the CREDENCE study continue to contribute to the evidence base to facilitate a better understanding in this critical area.” said Hywel Day, Managing Director Napp Pharmaceuticals Ltd.
In the UK, canagliflozin is indicated for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise. The initiation dose is 100mg once daily in adults with an eGFR of ≥ 60 mL/min/1.73m2 and can be increased to 300mg once daily if tighter glycaemic control is needed.7 Canagliflozin should not be initiated if eGFR is < 60 mL/min/1.73m2.7 In patients tolerating canagliflozin whose eGFR falls persistently below 60 mL/min/1.73m2 the dose should be adjusted to or maintained at 100mg once daily. Canagliflozin should be stopped if eGFR falls persistently below 45 mL/min/1.73m2.7
Notes to editors:
About the CREDENCE clinical trial
The CREDENCE study was the first dedicated outcome trial evaluating renal and CV outcomes in people with type 2 diabetes and chronic kidney disease with a sodium glucose co-transporter 2 (SGLT2) inhibitor. It was a phase 3, randomised, double-blind, event-driven, placebo-controlled, parallel-group, 2 arm multi-centre study of the effects of canagliflozin on renal and CV outcomes in subjects with type 2 diabetes and chronic kidney disease.8 In particular, it compared the efficacy and safety of canagliflozin versus placebo at preventing clinically important kidney and CV outcomes in patients with type 2 diabetes and chronic kidney disease when used in addition to standard of care, including a maximum tolerated daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).8
The primary results, published in April 2019, showed that the CREDENCE study met its primary endpoint by demonstrating that canagliflozin reduced the risk of composite doubling of serum creatinine, end-stage kidney disease (ESKD) and renal or CV death by 30% [HR: 0.70; 95% CI: 0.59 to 0.82; p=0.00001]. Furthermore, the CV results from CREDENCE found canagliflozin significantly reduced major CV events in the overall study population, including reducing the risk of CV death, heart attack or stroke by 20% (HR: 0.80; 95% CI: 0.67 to 0.95; p=0.01) and risk of CV death or hospitalization for heart failure by 31% (HR: 0.69; 95% CI: 0.57 to 0.83; p<0.001) and hospitalization for heart failure alone by 39% (HR: 0.61; 95% CI: 0.47 to 0.80; p<0.001).8
Canagliflozin is a member of a class of drugs known as SGLT2 inhibitors., SGLT2 inhibitors contribute to controlling blood glucose levels via the kidney. As glucose is filtered from the blood into the kidneys, it is reabsorbed back into the bloodstream. An important transport carrier in the kidneys for this reabsorption is called sodium glucose co-transporter 2 (SGLT2). Canagliflozin selectively inhibits SGLT2, and, as a result, promotes the loss of glucose via the urine, lowering blood glucose levels in adults with type 2 diabetes. This mechanism of action is independent of insulin.10
Canagliflozin is approved in the European Union for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance or contraindications and in addition to other medicinal products for the treatment of diabetes.7 Approval was based on a comprehensive global Phase 3 clinical trial programme.7,
About type 2 diabetes
Type 2 diabetes is caused by long-term high levels of sugar (glucose) in the blood. Type 2 diabetes is one of the most common long-term health conditions in the UK and typically occurs in older and overweight patients, though it is now being seen in ever-younger patients.12, It is caused by a combination of sedentary lifestyle, unhealthy diet and/or genetic factors.12,13 A number of factors can increase the risk of developing type 2 diabetes, including obesity.12,13 Obesity, specifically excess abdominal fat, can make the body less sensitive to insulin, causing a resistance by disrupting the function of insulin responsive cells and therefore the cells’ ability to respond to insulin, leading to higher blood sugar levels (hyperglycaemia).12,13
If not well controlled, type 2 diabetes can lead to long-term complications such as; heart disease, stroke, kidney damage (nephropathy), eye disease (retinopathy) and peripheral nerve damage (neuropathy).13,
About Napp Pharmaceuticals Ltd
Napp Pharmaceuticals Limited is a UK pharmaceutical company established in the 1920’s and based in the heart of the Cambridge science community. Focused principally in the areas of diabetes, respiratory, cancer, arthritis and gastroenterology, we have worked side by side with the NHS since its inception. As the UK healthcare environment has evolved, so has Napp, ensuring we have the right expertise to mirror what the NHS needs from us, understanding NHS priorities and what influences and drives decision-making.
We are part of a worldwide network of independent companies, which gives us the flexibility to make locally driven decisions quickly. We have developed our working practices to ensure we can be agile, and act fast and efficiently, in order to help our partners deliver sustainable healthcare solutions that ultimately improve patient outcomes. We aim to bring value-added medicines to the NHS by building effective partnerships. This is innate in the way we work because we are a partnership-based organisation, placing it at the heart of everything we do and every relationship, from our wholesale distributors to NHS decision-makers.
We are extremely proud of our heritage in partnership working, which is centred around building and developing mutually beneficial, enduring partnerships that are open and based on respect – this is how we have built our reputation as a partner of choice.
For more information please contact or visit:
National Kidney Federation: https://www.kidney.org.uk
Tel: +44 (0)1223 393191
Clark Health Communications
Phone: +44 (0) 207 4921900