Standards of medical care in diabetes – 2017: summary of revisions
Diabetes Care. DOI: https://doi.org/10.2337/dc17-S003
In stark contrast to guidelines from the National Institute for Health and Care Excellence (NICE), which in the case of type 2 diabetes took over 5 years to be updated, the American Diabetes Association (ADA) reviews its ‘Standards of Medical Care in Diabetes’ on an annual basis. It also sensibly provides a summary of the changes so that busy clinicians don’t need to trawl through the entire Diabetes Care supplement (134 pages). The changes are wide-ranging, from an inclusion of psychosocial aspects of therapy in all areas of diabetes care, to a discussion of evidence for diabetes screening in dental practice. More specific advice relates to periodic vitamin B12 assessment in patients taking metformin and less focus on ACE-inhibitors for the treatment of hypertension (thiazides and calcium channel-blockers are given equal prominence). Important from a clinical trial perspective is the redefinition of clinically significant hypoglycemia as a glucose level below 3.0 mmol/L (rather than 4.0mmol/L) and acknowledgement of the positive outcomes from recent cardiovascular studies of newer diabetes therapies. Well worth a read.
Exploring the characteristics of suboptimally controlled patients after 24 weeks of basal insulin treatment: an individualized approach to intensification
Kamlesh Khunti et al. Diabetes Research and Clinical Practice. DOI: http://dx.doi.org/10.1016/j.diabres.2016.11.028
The authors present a post hoc analysis of the SOLVE study. This was an industry-sponsored 24-week, international, observational study which examined 17,374 patients with type 2 diabetes (T2DM) inadequately controlled on oral antidiabetic drugs (OADs) who went on to receive once-daily insulin. Patients were divided according to the achieved HbA1c (above or below 7.0% [<53.0 mmol/mol] at their final assessment. The baseline characteristics which were independently associated with ‘suboptimal control’ included higher baseline HbA1c (odds ratio [95% confidence interval]: 1.56 [1.50;1.62]; p < 0.0001), body mass index (1.03 [1.02;1.04]; p < 0.0001), longer duration of diabetes (5–10 years: 1.44 [1.25;1.66]; >10 years: 1.44 [1.17;1.77]; p < 0.0001), and greater number of OADs (two OADs: 1.27 [1.12;1.44]; >2 OADs: 1.38 [1.14;1.66]; p = 0.0003). Unfortunately, this almost perfectly describes the typical phenotype of UK patients who are initiated on basal insulin. Worse still, apart from the HbA1c, it also describes the sort of patient who would receive insulin when the current NICE guidelines are followed. Perhaps basal insulin shouldn’t be the treatment of last resort.
Lack of evidence to guide deprescribing of antihyperglycemics: a systematic review
Cody D. Black et al. Diabetes Therapy. DOI: 10.1007/s13300-016-0220-9
This is an interesting area which, I suspect, many clinicians have not given a great deal of consideration (I admit that I hadn’t). The authors begin by highlighting that good clinical management of type 2 diabetes (T2DM) recognises the risk of hypoglycaemia in frail and elderly patients and the implication that this will involve withdrawal of antidiabetic drugs in many cases (they term this ‘deprescribing’). They then go on examine evidence from all studies evaluating the effects of deprescribing in older adults with T2DM, searching MEDLINE, EMBASE, and the Cochrane Library. They managed to identify only two controlled before-and-after studies which were both ‘of very low quality’. One study found that an educational intervention decreased glibenclamide use while not compromising glucose control. The other reported that cessation of antihyperglycemics in elderly nursing home patients resulted in a non-significant increase in HbA1C. No significant change in hypoglycemia rate was reported but only one study had this as an outcome measure. The manuscript has essentially identified an evidence-free zone, which researchers should be encouraged to fill.
Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy
Thomas Nyström et al. Diabetes Research and Clinical Practice. DOI: http://dx.doi.org/10.1016/j.diabres.2016.12.004
The progressive nature of T2DM ensures that drug therapy requires regular review and escalation. It is widely accepted by all international guidelines that Metformin should be used first line but after this, individualised treatment choices should be considered. The last few years have resulted in a plethora of drug classes with most health care professionals using insulin after oral failure. Cardiovascular outcome studies have shown the DPP4 inhibitors (gliptins) to be safe whilst at the same time others have shown that tight control using insulin may actually increase mortality possibly due to an increased incidence of hypoglycaemia. This Swedish study compared the risk of all-cause mortality and severe hypoglycaemia with patients started on either insulin or a gliptin after Metformin. The population was older (mean age 65) and had significant co-morbidities including a high incidence of established macrovascular disease. Insulin treated patients had a higher risk of mortality and severe hypoglycaemia than those on a gliptin. The cause for the increased mortality is not clear but the incidence of hypoglycaemia is probably relevant.
Lowest glucose variability and hypoglycemia are observed with the combination of a GLP-1 Receptor agonist and basal insulin (VARIATION study)
Harpreet S. Bajaj et al. Diabetes Care. DOI: https://doi.org/10.2337/dc16-1582
Glucose variability has been identified as a predictor of hypoglycemia and has been found to be related to intensive care unit mortality. Other evidence suggests a link between it and micro and macrovascular complications of diabetes as well as being predictive of severe hypoglycaemia in T1DM and non-severe hypoglycaemia in T2DM. Despite multiple available insulin regimes, it is unclear as to which will reduce glucose variability. This cohort study used continuous glucose monitoring (CGM) in patients with well controlled diabetes on a number of regimes including basal insulin and a GLP1 agonist, twice daily premixed insulin, basal bolus and basal insulin plus a variety of oral agents. The lowest glucose variability and incidence of hypoglycaemia was found in the group treated with basal insulin and a GLP1 agonist. This is likely to be due to the synergistic properties of this regime which target fasting and post prandial glucose excursions. The reduction in hypoglycaemia may contribute to emerging evidence regarding cardiovascular risk reduction with GLP1 analogues.