Journal Watch

Prepared for IDDT by Jim Young

May 2015

High strength, fixed combination and biosimilar insulin products: minimising the risk of medication error
Medicines and Healthcare Products Regulatory Agency

Several new high strength insulin products are now on the market. The European Medicines Agency is consulting on guidance to minimise the risk of medication error. It is likely that further such insulin products will come to market over the next few years. This draft guidance summarises ways to minimise the risk of medication errors with high strength, fixed combination and biosimilar insulin products already on the market. We are encouraged to comment on the risk minimisation strategy for high strength and fixed combination insulin products which is being developed by the European Medicines Agency. The consultation is open until 14 June 2015.
https://www.gov.uk/drug-safety-update/high-strength-fixed-combination-and-biosimilar-insulin-products-minimising-the-risk-of-medication-error

 

A practical review of insulin pen devices
Teresa L. Pearson. EMJ. EMJ Diabet. 2014;2:58-64.

Abstract: Since the advent of insulin pens in 1985, there have been ongoing improvements providing several advantages over the traditional vial and syringe method of insulin delivery. In recent years, pens have become increasingly user-friendly, and some models are highly intuitive to use, requiring little or no instruction. Despite this progress, there remains to be disparity in access to insulin pens to people with diabetes in various countries. There is a need for improved awareness of the benefits of insulin pens among healthcare professionals. Continual advances have been made to address patient needs such as improved technology to make them easier to use; less painful; more discreet and convenient; and more accuracy for small doses of insulin, as well as the incorporation of a memory function, all contribute to an insulin delivery device that allows the patient to better manage their diabetes anytime and anyplace, without the bulk and challenge of carrying a vial and syringe. These advances have resulted in increased patient satisfaction with insulin pens and most importantly, all of these benefits improve adherence and result in improved clinical outcomes. This review highlights these benefits of insulin pen use and presents the issues to be considered when helping patients decide on the insulin pen that will best suit their needs.
http://emjreviews.com/therapeutic-area/diabetes/practical-review-insulin-pen-devices/

 

A decade in diabetes specialist services, 2000 to 2011, in England: the views of consultant diabetologists and diabetes specialist nurses amidst persistent healthcare delivery change
C. A. Gosden et al. Diabetic Medicine. Doi: 10.1111/dme.12786

 This study set out to assess the impact of continual major National Health Service reorganization on commissioning, organizational and delivery arrangements for secondary care diabetes services. It explored how consultant diabetologists and diabetes specialist nurses perceived the issues facing diabetes specialist services in 2011 and how these have changed in the preceding decade. It was found that there was a willingness to innovate and work differently to improve services; however, clinicians must be supported through organizational changes to ensure people with diabetes receive high-quality care. The authors note that the disruptive nature of organizational change was a recurrent theme throughout the decade. They assert that periods of stability must exist within commissioning to allow relationships, which are key to integration, to be maintained and permit service improvements to develop.
http://onlinelibrary.wiley.com/doi/10.1111/dme.12786/abstract

 

Continuous glucose monitoring used with an insulin pump: should we recommend it to people with diabetes and can we afford it?
G. A. Hitman. Diabetic Medicine. Doi: 10.1111/dme.12759

The authors of this paper remind us that one of the classic messages from the Diabetes Control and Complications Trial (DCCT) was that improvement in glycaemic control was possible by intensifying insulin regimes, which led to a dramatic reduction in microvascular disease but at the expense of hypoglycaemia. Using insulin pump therapy (continuous subcutaneous insulin infusion), many people with Type 1 diabetes are getting closer to achieving HbA1c targets than is possible using a basal-bolus regime; however, they also state that there are a cohort of patients who have difficulty recognising hypoglycaemic symptoms and that these people are at particular risk at night. In this group of people the use of a real-time continuous glucose monitoring system, in addition to continuous subcutaneous insulin infusion, is an important facet of their everyday life. Currently, the continuous glucose monitoring system can be free-standing or part of a closed feedback loop whereby, once the glucose crosses a certain pre-set threshold, the insulin delivery will be suspended for a set time period; so-called glucose sensor-augmented insulin pump therapy. There is good evidence of the therapeutic benefit of continuous glucose monitoring for reducing HbA1c alongside a reduction of hypoglycaemic episodes. The authors assert that unfortunately, in the UK and in many countries, whilst many providers accept the use of insulin pumps, this is not the case for continuous glucose monitoring, and that the availability of which in the UK has become a postcode lottery, depending who is funding the patient’s healthcare.
http://onlinelibrary.wiley.com/doi/10.1111/dme.12759/full

 

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics
Paolo Pozzilli et al. Diabetes/Metabolism Research and Reviews. Doi: 10.1002/dmrr.2653

The authors of this paper state that for continuous subcutaneous insulin infusion (CSII) the insulins of choice are the rapid-acting insulin analogues (RAIAs), insulin aspart, insulin lispro, and insulin glulisine. They note that the association between CSII and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. Use of CSII is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available RAIAs are approved for use in adult, paediatric, and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections (MDI), CSII is cost-effective in selected patient groups. This comprehensive review, which focuses on the European situation, summarises evidence for the efficacy and safety of CSII, particularly when used with RAIAs, in adult, paediatric, and pregnant populations, discusses relevant European guidelines, reviews issues that surround use of this technology, summarises the effects of CSII on patients’ health-related quality of life (HRQOL), reviews relevant pharmacoeconomic data, and discusses recent advances in pump technology, including the development of closed-loop ‘artificial pancreas’ systems.
http://onlinelibrary.wiley.com/doi/10.1002/dmrr.2653/abstract

 

UK service level audit of insulin pump therapy in paediatrics
A. Ghatak et al. Diabetic Medicine. Doi: 10.1111/dme.12782

Following the issue of guidelines for the use of continuous subcutaneous insulin infusion by NICE in 2008 the authors conducted an audit of insulin pump therapy in the UK. Of the 176 UK centres identified as providing pump services, 166 (94.3%) participated in this study. A total of 5,094 children and young people were identified as using continuous subcutaneous insulin infusion (19% of all paediatric patients with Type 1 diabetes). The report gives comprehensive details of service delivery and concludes with the observation that although the number of children and young people on continuous subcutaneous insulin infusion therapy is consistent with numbers estimated by NICE, there is a worrying lack of funded healthcare professional time. The audit also identified gaps in the provision of structured education and absence of written inpatient guidelines.
http://onlinelibrary.wiley.com/doi/10.1111/dme.12782/abstract

 

Is the current standard of care leading to cost-effective outcomes for patients with type 2 diabetes requiring insulin? A long-term health economic analysis for the UK
W.J. Valentine et al. Diabetes Research and Clinical Practice. Doi: http://dx.doi.org/10.1016/j.diabres.2015.04.023

In this investigation clinical data was derived from a retrospective analysis of 3,185 patients with type 2 diabetes on basal insulin in The Health Improvement Network (THIN) general practice database. In total, 48% (614 patients) intensified insulin therapy, defined by adding bolus or premix insulin to a basal regimen, which was associated with a reduction in HbA1c and an increase in body mass index. It was found that immediate insulin intensification was associated with improvements in life expectancy, quality-adjusted life expectancy and time to onset of complications versus no intensification or delaying intensification by 2, 4, 6, or 8 years. Direct costs were higher with the insulin intensification strategy (due to the acquisition costs of insulin). However, the conclusion was that although associated with improved clinical outcomes, insulin intensification as practiced in the UK has a relatively high cost per quality-adjusted life year (QALY) and may not lead to cost-effective outcomes for patients with type 2 diabetes as currently defined by UK cost-effectiveness thresholds.
http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(15)00205-3/abstract

 

Factors associated with relational coordination between health professionals involved in insulin initiation in the general practice setting for people with type 2 diabetes
Jo-Anne Manski-Nankervis et al. Journal of Advanced Nursing. Doi: 10.1111/jan.12681

This study examined the associations between the characteristics of general practice settings and primary healthcare providers (general practitioners and practice nurses) and the degree of relational coordination for the task of insulin initiation for type 2 diabetes between primary healthcare providers and diabetes specialists. It drew on the results from surveys completed by general practitioners and practice nurses participating in the Stepping Up trial. Data on demographics, practice characteristics and relational coordination were collected between October 2012 and June 2014. It found that the expanded role and experience of practice nurses in diabetes care increased and that had the potential to deliver more effective chronic disease management in general practice, and that practice and health professional characteristics should be taken into account when designing models of care to increase insulin initiation.
http://onlinelibrary.wiley.com/doi/10.1111/jan.12681/abstract

 

Diabetic kidney disease: pathophysiology and therapeutic targets
Stephanie Toth-Manikowski and Mohamed G. Atta.  Journal of Diabetes Research. Doi: http://dx.doi.org/10.1155/2015/697010

Over the past two decades, there has been significant clarification of the various pathways implicated in the pathogenesis of Diabetic Kidney Disease (DKD). Nonetheless, very little has changed in the way clinicians manage patients with this disorder. Indeed, treatment is primarily centered on controlling hyperglycemia and hypertension and inhibiting the renin-angiotensin system. The purpose of this review is to describe the current understanding of how the hemodynamic, metabolic, inflammatory, and alternative pathways are all entangled in pathogenesis of DKD and to detail the various therapeutic targets that may one day play a role in quelling this epidemic. The paper concludes with the observation that the treatment of DKD will likely require a multifaceted approach given the numerous pathways involved in the diabetic kidney.
http://www.hindawi.com/journals/jdr/2015/697010/

 

Deciphering metabolic messages from the gut drives therapeutic innovation
Daniel J. Drucker. The 2014 Banting Lecture (Diabetes). Doi: 10.2337/db14-1514

Gut peptides convey nutrient-regulated signals to the enteric nervous system and to distal organs, and act as circulating hormones secreted in the basal and postprandial state. This study provides an overview of the actions of glucagon-like peptide (GLP)-1 and GLP-2, the two major enteroendocrine L-cell peptides. The multiple metabolic actions of GLP-1 enable reduction of glycemia and body weight in diabetic and obese subjects, providing the opportunity to reduce glycemia in human subjects with diabetes with a low risk of hypoglycemia. GLP-2 plays a key role in the control of energy absorption and in the integrity of the intestinal mucosa. GLP-1 and GLP-2 are both cleaved by dipeptidyl peptidase-4 (DPP-4); hence, inhibition of DPP-4 activity enables yet another pathway for potentiation of incretin action and the therapy for type 2 diabetes. The author of this review calls on 30-year experience with the elucidation of gut hormone action and, where possible, highlights the therapeutic implications of preclinical studies and future opportunities for incretin research.
http://diabetes.diabetesjournals.org/content/64/2/317.long