Glimmer of hope for obese type 2 patients

Back in the days of UKPDS it was firmly established that insulin-initiation in patients with type 2 diabetes leads, on average, to a weight gain of around 7Kg in the first 12 months after initiation.

Patients and their doctors do not like this. The patients feel disempowered as they watch their weight remorselessly climb and their doctors have a sneaking suspicion that they are doing little more than ‘fuelling the fire’ of insulin resistance.

Although the latter concern has a strong theoretical basis, we should remember that even with the observed weight gain, there is strong evidence that intensively insulin-treating T2DM leads to better outcomes than not doing so.

Nevertheless, the weight issue remains and is only becoming more of a problem as the background average BMI in the population increases. In 2007, a new class of T2DM drug was launched – the GLP1 agonists and indeed initial experience has been encouraging with the ABCD UK national audit of exenatide reporting a mean 0.7% HbA1c reduction and a mean 5.9Kg weight loss in the first six months with broadly acceptable side effect and safety profile (to date).

Of course we do not yet know if these results, which after all are only surrogate end points, will translate ultimately in to reduced mortality and morbidity but for now the portents are good. Thus, for the first time in T2DM there has been a meaningful alternative to insulin inititiation, and more importantly one which offers realistic hope of weight loss, when the old metformin/sulphonylurea combination is no longer cutting the mustard.

However, until very recently, a large and important group or patients has been excluded from the party – those whose HbA1c is so way out of range or whose beta cell exhaustion so advanced (or both) that insulin is mandated. Of course some have already been (perhaps quite rightly) combining insulin with GLP1 agonsists “off license” and again the ABCD UK national audit gives us a useful snap shot of this situation, showing that across the UK already ~30% of prescriptions for exenatide were written in combination with insulin.

However, it will come as a relief that this practice has finally been officially sanctioned. Many of you will have received a communication from Lilly/Amylin in the last couple of weeks that twice daily exenatide is now licensed in Europe for co-prescription with any basal insulin (and metformin plus/minus pioglitazone). Although the study that led to this license extension was performed with insulin glargine, the EMA’s decision pragmatically and sensibly does not restrict the approval to lantus.

Encouragingly, there was no more hypoglycaemia in the exenatide/glargine arm of the study than in the glargine/placebo arm.

Although it will remain essential to monitor patient's responses in terms of weight and HbA1c improvement, to stop this costly combination where there is little/no benefit and to remain philosophical about its use while there is an absence of hard evidence of long term benefit, this step offers one more bit of good news to patients.

I think the next challenge for this interesting area of pharmacotherapy is to see what guidelines NICE lays down around the GLP1-insulin combination in its next iteration of CG66-CG87-type 2 diabetes clinical guidance.

Tags for this article: GLP1 agonists

The author - Dr Jeremy Turner

Jeremy Turner A consultant diabetologist and endocrinologist in Norfolk, and author of Diabetes Bible

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My blog expresses my personal views on the rapidly advancing field of diabetes. It is aimed at fellow physicians and is not offering medical advice to readers. I will not respond to requests for clinical advice. If you have health concerns please contact your GP or specialist.

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