NICE has not published guidance specifically related to lixisenatide, but the place of the drug in therapy will be included in the update of the NICE clinical guideline for the management of type 2 diabetes. The publication date for this guideline is to be confirmed.
NICE recommends the use of exenatide or liraglutide in dual or triple therapy in addition to metformin, a sulfonylurea or a glitazone in certain circumstances (see the Introduction for more information). The European Medicines Agency (EMA) noted in its public assessment report for lixisenatide that the effect of lixisenatide on HbA1c, when added on to metformin, was clinically relevant. However, the 0.8–0.9 percentage point mean reduction in HbA1c from baseline in the lixisenatide groups in GetGoal-P and GetGoal-M were slightly less than the 1.0 percentage point (11 mmol/mol) reduction specified in NICE guidance as a criterion for continuing treatment with exenatide or liraglutide in triple or dual therapy beyond 6 months, and the mean difference from placebo was about half of that.
Although the EMA concluded in its public assessment report for lixisenatide that non-inferiority to exenatide had not been shown robustly, it stated that the absolute mean reduction in HbA1c and body weight from baseline produced by lixisenatide in GetGoal-X was of clear clinical relevance, and that lack of proof of non-inferiority could be acceptable considering other benefits, such as once-daily dosing and a lower incidence of nausea and hypoglycaemia.
Weight loss has been seen as a possible pleiotropic effect of glucagon-like peptide-1 (GLP-1) mimetics and is a criterion within NICE guidance for continuing treatment with exenatide or liraglutide in triple therapy in addition to metformin and a sulfonylurea beyond 6 months. There was no statistically significant effect from lixisenatide on body weight compared with placebo in either GetGoal-M or GetGoal-P (lixisenatide plus oral agents). In the 2 trials of lixisenatide in conjunction with basal insulin, body weight reduced to a greater extent with lixisenatide than placebo in GetGoal-L and increased to a lesser extent with lixisenatide than placebo in GetGoal-Duo1. The EMA concluded in its public assessment report for lixisenatide that, overall, the mean difference in body weight with lixisenatide compared with placebo was approximately 1 kg, and that this was of clear clinical relevance and advantageous compared with the increase in weight with some other therapeutic options.
NICE guidance does not currently include the use of any GLP-1 mimetic in combination with insulin. The results of GetGoal-L and GetGoal-Duo1 needs to be considered in that context and also in terms of the likely clinical significance of the observed difference in HbA1c from baseline and in comparison with placebo.