Diabetes – lixisenatide

With the inexorable increase in Type II diabetes there is a real need for new drug treatments that improve glucose control

With the inexorable increase in prevalence of Type II diabetes thanks to bad diet and lack of exercise, there is still a real need for new drug treatments that give better glucose control. One of these, lixisenatide, was discovered by Zealand Pharma, and commercialised by Sanofi.1 The modified exendin-4 peptide acts as a glucagon-like peptide-1 (GLP-1) agonist. GLP-1 is a naturally occurring peptide that is released after eating, and suppresses the secretion of glucagon from pancreatic alpha cells, as well as stimulating insulin release from pancreatic beta cells.

Numerous randomised, double-blind, placebo-controlled, parallel-group Phase III clinical trials have taken place in adults with inadequately controlled Type II diabetes, looking at the effect of daily subcutaneous doses of lixisenatide as an add-on therapy in combination with other antidiabetic agents or insulin.

For example, in a 13-week study in 542 patients, subjects were given metformin plus 5, 10, 20 or 30µg lixisenatide once or twice a day or placebo.2 The drug significantly improved mean HbA(1c),with better results achieved on the twice-daily schedule. Dose-dependent improvements were also seen for both fasting and post-prandial blood glucose levels, and weight loss of 3–4kg was also achieved. The most common side-effect was mild to moderate nausea.

Another trial was carried out in combination with pioglitazone.3 Subjects were given 20µg once-daily doses of lixisenatide or placebo in addition to their existing piaglitazone ± metformin therapy for 24 weeks. Again, the new drug gave a significantly greater reduction in HBA(1c) than placebo. Another trial gave subjects similar doses of lixisenatide or placebo in combination with insulin ± metformin.4 Insulin doses were kept constant throughout the 24-week study, and again much better reductions in HBA(1c) were achieved in the lixisenatide group.

It has also been investigated as monotherapy, with 361 patients in a 12-week study given once daily step-up doses from 10µg up to a maximum of 20µg or placebo.5 Again, it significantly improved HbA(1c) compared with placebo, with marked improvements in 2-h postprandial glucose levels. A significant decrease in fasting plasma glucose was also seen.


1. M. Christensen et al. IDrugs 2009, 12, 503

2. R.E. Ratner et al. Diabet. Med. 2010, 27, 1024

3. M. Pinget et al. 47th EASD 2011 (Lisbon, 12-16 Sep), Abst. 810

4. R. Aronson et al. 48th EASD 2012 (Dublin, 1-5 Oct), Abst 3

5. V.A. Fonseca et al. Diabetes Care 2012, 35, 1225