On 8th November 2012, the Federal Drugs Administration (FDA) in the United States received guidance from its Endocrinologic and Metabolic Drugs Advisory Committee on the application for a license for degludec insulin and it’s combination preparation degludec/aspart. Degludec has a protracted delivery following subcutaneous injection allowing for flexibility in the timing of its once daily dosing and low risk of night-time hypoglycaemia. Although the committee had voted in favour of a license, this was only by an 8-to-4 split and there had been a unanimous recommendation (12:0) for a study of the cardiovascular (CV) safety of degludec. This is in marked contrast to the opinion of the European Medicines Agency (EMA), which recommended the granting of a marketing authorisation for degludec on 18th October 2012 with no apparent concerns over CV safety. The Japanese authorities were also satisfied with the CV analyses. So, why should there be this divergence of opinion and who has got it right?
Archives for 2012
Traditionally, the management of diabetes has centred around pharmacological intervention to treat hyperglycaemia and cardiovascular risk factors, often with minimum input from a health care professional. However, from a patient perspective, daily living consists of multiple choices such as appropriate dietary intake, physical activity as well as drug compliance. Over recent years, the importance of patient education has developed as a means to acquire the skills necessary for active responsibility in the day to day self management of their condition. Indeed, this is recognised in the 2008 NICE guidelines for diabetes as well as the 2011 NICE quality standards.
The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) study was presented at the American Diabetes Association (ADA) meeting in June 2012 and simultaneously published in the NEJM. It was a large trial (>12,500 participants), which sought to establish if early use of basal analogue insulin, titrated according to fasting blood glucose levels, would reduce cardiovascular events. ‘Early use’ was certainly the case since 12% of subjects had ‘pre-diabetes’ and 6% were newly diagnosed, meaning that 40% of participants were on no hypoglycaemic therapy at baseline. All were, however, at high cardiovascular risk (defined according to a previous event or presence of risk factors such as albuminuria or left ventricular hypertrophy). Trial subjects received glargine or no treatment in an open design but were also randomised to double blind therapy with omacor or placebo to assess the impact of omega 3 fatty acids in this scenario.
Facebook , Twitter, the last few years have shown the ease of communication using technology where all aspects of someone can be followed on line and where a person’s once confidential information now seems to be open to the world. Compare that to communication between health care professionals involved in a patients care. This is of particular importance when it comes to diabetes and the multi-disciplinary approach taken including input from doctors, nurses, podiatrists, dieticians, retinal screeners – the list goes on. The information divide is most marked between primary care (where most practices are paperless) and secondary care (where paper predominates or a variety of clinical information tools exist). The major issue from all these different systems is the lack of continuity of care, duplication of care (such as foot screening) and delays in passing on changes to a patients’ management.
The adolescent and young adult years are difficult enough for a young person to handle, the additional burden of managing diabetes making this even harder. Although there are a handful of patients with Type 2 diabetes at this age – usually from certain ethnic groups or with a variety of genetic syndromes, the vast majority of patients have Type 1 diabetes. Whilst this is often diagnosed in relatively early childhood, the peak age of diagnosis is at 10-14 years. As such, the majority of these patients take insulin with all the issues that this involves.
A recent publication (1) reported the identification of another ten genes which may predispose to type 2 diabetes (T2DM), bringing the current total to around fifty. However, the impact of these genetic studies from a clinical perspective remains minimal. Forty years after the discovery of the first genes involved in diabetes susceptibility, should we be querying the value of expensive ‘factory floor’ genetics?
Whilst significant time and effort is spent looking after patients with diabetes, this is merely the tip of a larger iceberg of people at risk of diabetes and cardiovascular. This ‘iceberg’ forms the basis for recent (July 2012) NICE guidance on preventing type 2 diabetes, risk identification and interventions for individuals at high risk . This guidance follows the adoption by the WHO of the use of HbA1c as a diagnostic tool (HbA1c >48mmol/mol/ 6.5%) and the identification of people with HbA1c 42-47mmol/mol (6.1-6.4%) as being at high risk – although it is acknowledged that this elevated risk may extend to people with an even lower HbA1c.
There are currently seven classes of antidiabetic agents for the treatment of type 2 diabetes (indeed, eight if you include bromocriptine, which has FDA approval for this use) but this is about to change with the launch of dapagliflozin which is expected later this year. ‘Dapa’ was given its European licence in April 2012 and is the first of a class of drugs which inhibit the action of the sodium-glucose transporter 2 (SGLT-2); three more are in development.
Diabetes Apps, are they a happy happenstance – where technology wins over pathology – or a counterproductive hypertrophy of data? This article will open this Pandora’s Box.
The number of Apps (application software) for smart phones has expanded exponentially in recent times: with hardware add-ons that enable glucose monitoring and the recording of data; the storage of data for patient self-care or for upload to the “Cloud” for access by their healthcare professionals. There are Apps that offer advice about diet, lifestyle, and disease management.
But are these Apps of real benefit to the patient and do they augment or retard physician interventions?
For anyone involved in diabetes care, the last few years have been characterised by a tidal wave of new cases all of whom have required education, self management advice and screening for complications, not to mention the escalation of drug therapy. Much of this clinical input is guided by nine care processes initially described in the Diabetes NSF over 10 years ago – glycaemia, BP, cholesterol, weight, smoking, renal function & microalbuminuria as well as foot and retinal screening.
Trials of metformin (MF) as an anti-cancer drug have recently begun, enhancing its reputation as a ‘wonder-drug’, effective over a spectrum of life-threatening diseases whilst being highly cost-effective. The cancer story began following reports (wildly exaggerated, in my view) that insulin glargine increased the risk of cancer but this was not seen in patients taking concomitant MF. Allied to its beneficial impact on cardiovascular (CV) outcomes, MFs first-line position in ALL diabetes guidelines seems to have been consolidated. But how strong is the evidence?
The inexorable rise of primary care diabetes over the past 10 years, with a mass transfer of patients from hospital clinics and the creation of community diabetes medical and nurse consultants may now be demonstrating a down-side.
A summary of the National Diabetes Inpatient Audit (NaDIA 2011) in England was recently published, this being the third snapshot of inpatient care for people with diabetes. NaDIA 2011 was carried out by diabetes teams in 188 acute sites on a nominated day in October, resulting in data on 11,866 inpatients.
The management of diabetic foot disease has recently come to attention following the publication in Diabetologia of evidence of variation in amputation rates across PCTs in England. Compared to the general population, patients with diabetes are 20x more likely to require lower limb amputation, costing the NHS £120m annually. 80% of these are thought to be avoidable. Following on from this, the recent National Diabetes in patient audit has once again highlighted the importance of foot care. Whilst only 9.5% of patients with diabetes are admitted as a result of their diabetes, 47% of this group were admitted with active foot disease. It is likely that this group of patients contribute significantly to the increased length of stay seen in diabetic patients. For other diabetic patients, only 22.4% of patients had a documented foot examination within 24 hours of admission.
In 2010, the medical press was full of stories concerning a link between the long-acting insulin analogue, glargine, and various forms of cancer. A year later, the French authorities banned pioglitazone, on the basis that it might increase the risk of bladder cancer. Although neither of these links have been substantiated (and both agents remain part of NICE guidance in the UK), the spectre of increased cancer risk has now fallen on a novel diabetes pipeline agent, threatening to slow its launch.
Pregnancy poses additional risks for women with diabetes. The most recent CEMACH (Confidential Enquiry into Maternal and Child Health) report continues to show that babies of women with diabetes are five times as likely to be stillborn, three times as likely to die in their first months of life and twice as likely to have major congenital malformation (this last number maybe higher as it is not adjusted for the higher rate of terminations where congenital malformations are found). Although the majority of mothers with pre-existing diabetes have type 1 diabetes, the proportion of births to women with diabetes is rising due to the rising numbers of young women with Type 2 diabetes. Worryingly, some of the latter group are only diagnosed in pregnancy.