Treatment for DM2 needs to be targeted at the diabetic phenotype (obese, IR, beta cell dysfunction, reduced beta cell mass, hyper-glucagonaemia, macrovascular risk, progressive disease).
GLP-1 analogues reduce weight, improve glucose-induced insulin secretion, increase beta cell growth and reduce apoptosis, inhibit glucagon, reduce gastric emptying and probably have cardiovascular beneficial effects.
A recent systematic review and meta-analysis including exenatide, exenatide LAR and Liraglutide is presented at the 2011 ADA. Weight loss was common to all trials with an overall average weight loss across the studies included of -2.8Kg. This compared with a rise in body mass in the studies involving insulin as the agent of choice when injection therapy is initiated. The overall difference between GLP-1 therapy vs insulin was 4.53Kg.
Hypoglycaemia risk is an important consideration as it results in reduced QOL for patients and affects concordance. There are also reasonable data to suggest that hypo may be linked to an increased mortality in DM2 when compared to those without hypo. GLP-1 therapy causes significantly less hypo than insulin.
In the recent meta-analysis there was a fall of around 3.5mmHg inSBP and 1.5 mmHg in DBP. Cholesterol also decreased and Liraglutide and Exenatide have been shown to improvesurrogate markers of vascular dysfunction.
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