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The rationale for combining GLP-1 receptor agonists with basal insulin

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The progressive nature of type 2 diabetes mellitus (T2DM) dictates the need for an individualised, stepped interventional approach. The current approach to treatment intensification includes the addition of increasingly complex insulin regimens that involve prandial insulin dosing. However, the more intensively diabetes is treated with many of the current treatment options, the greater the risk of hypoglycaemia, weight gain and, possibly, cardiovascular mortality.13 One of the key challenges in patient management is how to achieve glycaemic goals while mitigating these risks.

Pharmacological approaches aimed at enhancing the incretin effect in T2DM have been pursued.4 Two main classes of incretin therapies are now in use: glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1 receptor agonists mimic the effects of endogenous GLP-1; they stimulate glucose-medicated insulin secretion and suppress glucagon secretion (Box 1). But, unlike DPP-4 inhibitors, they have the additional clinical benefits of delaying gastric emptying and decreasing appetite.