Do Genetics Explain Variability in Weight-Loss Response to Liraglutide?

sharma-obesity-dna_molecule9As with any medication (for anything!) not everyone responds the same.

Now a small study by Mojca Jensterle and colleagues from Ljubljana, published in the European Journal of Clinical Pharmacology, reports that genetic variability in the GLP-1 receptor gene may predict the variability to the human GLP-1 analogue liraglutide, now approved for obesity treatment in the US, Canada and Europe.

In their study, Jensterle and colleagues examine the realationship between two common alleles (variants) of the GLP-1 receptor in 57 women with obesity and polycystic ovary syndrome.

All women were treated with liraglutide 1.2 mg QD s.c (well under the 3.0 mg QD dose approved for obesity treatment) for 12 weeks.

Twenty of the participants were classified as strong responders (>5% weight loss), who lost about 7.4 Kg, whereas 37 were considered poor responders losing only 2.2 Kg.

Carriers of at least one rs10305420 allele were about 70% less likely to be a high responder than individuals with two wild-type alleles. Similarly, carriers of at least one rs6923761 allele were about three times as likely to high responders compared to homozygous carriers of the wild type.

Although my previous work in these type of genetic studies have made me highly critical (not to say sceptical) of these types of small studies, the notion that genetic variability in the GLP-1 receptor (the molecular target of liraglutide) may well lead to differences in response is not all that far fetched.

Thus, whether true or not, I have little doubt that indeed much of the variability in pharmacological response to liraglutide (or for that matter any other drug for anything) may well be determined by genetics.

Whether testing people for genetic markers before starting a specific treatment will ever become reality for obesity and whether or not, the genetic variability seen in this study will still be seen when lirglutide is used at the actual dose approved for obesity treatment remains to be seen.

In the meantime, the easiest way to see who responds and who does not is to try it. This why the regulatory approval of liraglutide for obesity comes with a simple stopping rule – if it doesn’t work for you – stop taking it!

Edmonton, Alberta

Disclaimer: I have received consulting and speaking honoraria from Novo Nordisk, the maker of liraglutide.