Management of hyperglycaemia in type 2 diabetes: a patient-centered approach
Inzucchi S. Bergenstal R et al. Diabetes Care. Doi: 10.2337/dc14-2441
We all know that diabetes care moves at such a fast rate, it can be very hard to keep an eye on what is going on. So helpfully this paper is an update on a previous statement, published in 2012. This valuable review looks at the current state of type 2 diabetes management. It is an excellent and up to date review which is well worth a read or if you want, there is also a very informative slide set which can be easily downloaded and read off line. The paper is a helpful summary of current knowledge and practice but it is good to see that the old favourite metformin is still number one for single treatment. Other options are also considered and injection therapy is not forgotten either. Personalisation of treatment is discussed and it is encouraging to read that overzealous treatment is also highlighted in some specific age groups. This is a very readable review article which neatly summarises current wisdom with input from a large number of experts.
Type 2 diabetes and cancer umbrella review of meta-analyses of observational studies
Tsilidis K. Kasimis J.et al. British Medical Journal. Doi: 10.1136/bmj.g7607
According to this paper “Almost 400 million people throughout the world have diabetes, 85-95% of who have type 2 disease.” An impressive and memorable statistic but we also know that cancer is common. There has been a suspicion that type 2 diabetes may be linked with a number of different cancers. The researchers performed an extensive literature search and carried out a detailed statistical analysis for this paper. They concluded that there was a lot of research in this area with many claims. However only a small number of cancers have a good evidence base to associate them with type 2 diabetes. The article stated “Evidence could be substantiated only for the associations between type 2 diabetes and risk of developing breast, intrahepatic cholangiocarcinoma, colorectal, and endometrial cancer”. Other malignancies may still have a link with type 2 diabetes but the evidence is not as strong. There is still a lot of work to prove the case, provide precise biological explanations as to why this happens but at least this paper helps to clarify current knowledge.
Metformin use reduction in mild to moderate renal impairment
Flory J. Hennessy S. JAMA Intern Med. Doi:10.1001/jamainternmed.2014.6936
Metformin is universally considered as the first drug of choice in treating Type 2diabetes. This positioning comes from the fact that the drug is not associated with hypoglycaemia or weight gain and is unique amongst hypoglycaemic agents due to its cardiovascular protective properties. However, despite these benefits, many patients are either not started on metformin or having their use stopped prematurely. Whilst some of this may be due to education about where to use this drug (although this is hard to believe given its position in all guidelines over the last few years), it is possible that concern over renal function is an issue. Whilst Creatinine levels are often used as a guide to stopping the drug (caution if >130µmol/l, stop if >150), many professional bodies feel that eGFR is a better method of measuring renal function (caution if <45, stop if <30). Using the creatinine values may result in the drug being stopped prematurely in many patients who would benefit. In keeping with this, the 2015 draft NICE guidance for Type 2 diabetes embraces eGFR only as a measure of renal function for patients on Metformin.
Evaluating biosimilar medicines
National Institute for Health and Care Excellence
Biosimilar insulin will soon become a therapeutic option and so the way NICE reviews biosimilars is important. In contrast to generic drugs, with simple chemical structures (considered identical to their reference medicine), biosimilars are copies of more complex biological medicines, often produced in living systems (yeast & bacteria). The complexity means that characteristics of biologic drugs cannot be exactly reproduced. Biosimilar glargine has been licenced for use in the EU and will become available when the patent on Lantus expires in 2015. To be deemed ‘biosimilar’, licencing authorities require: similar pharmacokinetic and dynamic characteristics to the original; similar clinical efficacy; and no clinically meaningful differences in immunogenicity or adverse event profile. To put this into context, biosimilar glargine satisfied all requirements with five abstracts at last year’s ADA meeting. Now NICE seems to be stating that once biosimilar glargine has been successfully passed a Technology Appraisal, then subsequent glargine biosimilars can be fast-tracked through the process. In contrast, the novel insulin degludec molecule is currently undergoing a large-scale cardiovascular outcome study to demonstrate safety.
Pharmacokinetics and pharmacodynamics of insulin glargine evening v morning T2D
Francesca Porcellati et al. Diabetes Care. Doi: 10.2337/dc14-0649
When basal-bolus regimes of insulin were first introduced, long-acting insulin was recommended as an evening injection. This reflected the less-than-24 hour profile of human insulin, and fear that patients would have no background insulin during the twilight period if it was administered during day-time. Availability of analogue basal glargine, with a longer, flatter profile seemed to remove this requirement with any-time dosing possible (so long as it was roughly the same time). Now, with the advent of ultra-long acting analogues (degludec, U300 glargine & PEGylated lispro), the pharmacokinetics (PK) and pharmacodynamics (PD) of glargine are under increased scrutiny. This paper shows that with morning administration, insulin glargine activity is greater in the first 0–12 hours whilst with evening administration, it is greater over 12–24 hours. However, glargine PK and PD were similar when analyzed by 24-hour clock time independent of administration time. The authors suggest this reflects circadian changes in insulin sensitivity in T2DM (lower at night/early morning versus afternoon). This could impact on the clinical response to new analogues, so clinicians need to be aware.