GLP-1 Receptor Agonists, Obesity And Psoriasis
Wednesday, September 7, 2011
I have previously discussed the not too uncommon association between obesity and psoriasis, a chronic, autoimmune disease that causes red, scaly patches to appear on the skin, and affects 2-3% of the population in Western countries.
Hogan and colleagues, St Vincent’s University Hospital, University College Dublin, Ireland, in a paper just published in Diabetologia, now report improvement of psoriasis in three obese patients with type 2 diabetes several weeks after the initiation of therapy with the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists exenatide and liraglutide.
Regular readers may recall that GLP-1 receptor agonists were recently introduced for the treatment of diabetes and are currently under investigation for the treatment of obesity.
In addition to the clinical improvement, with reduced itching and/or a reduction in Psoriasis Area and Severity Index (PASI) scores, they also provide evidence that GLP-1 receptor agonist treatment had immunological effects in that it increased the number of natural killer T (NKT) cells in the circulation and reduced the number of invariant NKT cells in the psoriatic plaques.
In an accompanying commentary, Drucker and Rosen from the University of Toronto, point out that apart from the ‘classical’ metabolic effects of GLP-1 (e.g. on the secretion of insulin and glucagon), GLP-1 receptors are also found in numerous immune cell subpopulations, including thymoyctes, splenocytes, bone marrow-derived cells, and regulatory T cells.
It is therefore biologically ‘plausible’ that administration of GLP-1 analogues could have anti-inflammatory effects on psoriasis (and perhaps other inflammatory abnormalities).
Obviously, a few cases do not yet make an indication, but they certainly suggest that this hypothesis may well be worthy of further study.
I certainly wonder, if any of my readers have experienced similar improvements in inflammatory conditions like psoriasis with the use of GLP-1 analogues.
AMS
Edmonton, Alberta
Hogan AE, Tobin AM, Ahern T, Corrigan MA, Gaoatswe G, Jackson R, O’Reilly V, Lynch L, Doherty DG, Moynagh PN, Kirby B, O’Connell J, & O’Shea D (2011). Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis. Diabetologia PMID: 21744074
Drucker DJ, & Rosen CF (2011). Glucagon-like peptide-1 (GLP-1) receptor agonists, obesity and psoriasis: diabetes meets dermatology. Diabetologia PMID: 21892687
Wednesday, September 7, 2011
I don’t have psoriasis myself, but my dad’s a fat type II diabetic, and he’s got it – or had when he was younger, anyway. Are exenatide and liraglutide the drugs’ trade names? If so, I’ll ask him if he’s taking them and how his psoriasis is doing.
Wednesday, September 7, 2011
Hi Dr. Sharma…
I can’t contribute to your question, but was wondering if you had any insight into long term changes in psoriasis patients following WLS. I had assumed that as part of metabolic syndrome, psoriasis would be improved by rapid weight loss and metabolic balance, but eight months later my own case is worse than ever. I haven’t seen any research on the matter and was hoping you could cover this in a future post.
Cheers!
Wednesday, September 7, 2011
It is a very interesting study. I might be stretching what I remember here, but I think about 30% of psoriasis sufferers have elevated uric acid (at least those with psoriatic arthritis). We used to find in practice that treatments that lowered uric acid improved symptoms in these patients. I believe I have seen data that GLP-1 agonists lower uric acid – so perhaps that is also part of the mechanism for improvement?
Friday, September 9, 2011
Very interesting! I had a patient in a clinical trial of once weekly exenatide (a new GLP-1 analog) vs placebo, who lost 35lb and had DRAMATIC improvement of her psoriasis, almost to the point of complete resolution. It could have been the weight loss alone that improved her psoriasis but it was so severe and so dramatically improved, that I really do think there was pharmacologic activity going on here (the randomization won’t be unblinded for years so it will be long before I know for sure).