Injectable weight loss medications such as tirzepatide and semaglutide have helped millions of Americans shed excess weight. Now, researchers are looking at pairing these glucagon-like peptide 1 (GLP–1) agonistsand dual GLP-1/ glucose-dependent insulinotropic polypeptide (GIP) receptor agonists with drugs that treat inflammatory diseases such as psoriasis to see if the combination boosts effectiveness.
TDD talked to several leading dermatologists about the potential synergy. Many of them are already on board and think that this combination will be the new standard of care for overweight or obese patients with psoriasis and other inflammatory conditions.
A Brief History of GLP-1 Agonists
First approved to treat diabetes under the brand name Ozempic, semaglutide (Novo Nordisk) received a U.S. Food and Drug Administration (FDA) nod as a weight-loss medication in June 2021 under the brand name Wegovy. Mounjaro (tirzepatide) was FDA-approved in spring 2022 for managing type 2 diabetes and greenlighted for chronic weight management in November 2023 as Zepbound (tirzepatide). Zepbound and Mounjaro are dual-agonist drugs, while Wegovy and Ozempic are single-agonist drugs.
Eli Lilly & Co. is set to begin recruiting for trials to test tirzepatide (Zepbound) with ixekizumab (Taltz) andis also exploring combination studies with Zepbound in inflammatory bowel disease too, according to media reports.
Mark G. Lebwohl, MD, the Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai and Professor and Chairman Emeritus of the Kimberly and Eric J. Waldman Department of Dermatology in New York City, and his team helped design the new trial, which will be launched soon.
“I predict that the combination of Taltz and Zepbound will be a powerful tool for treating overweight psoriasis patients,” he says. “Weight loss clearly improves the response to drugs, not to mention a myriad of obesity- and psoriasis-related comorbidities. I am already prescribing weight loss drugs, and I believe many of us will be doing so in the coming years.”
Hidradenitis suppurativa (HS) patients may also benefit from combination therapy that includes weight loss drugs, Dr. Lebwohl says.
The combination makes intuitive sense, according to George Martin, MD, Founder of Maui Derm and a dermatologist in Kihei, HI. “It has been known for years that weight reduction leads to greater therapeutic outcomes in inflammatory diseases [including] psoriasis and psoriatic arthritis, rheumatoid arthritis, HS, and others,” he says.
White adipose tissue is the largest endocrine organ that secretes systemic pro-inflammatory adipokines and cytokines. “Although not completely understood, weight gain and obesity result in dysfunctional adipocytes as well as an accumulation of immune cells in the fatty tissue,” Martin says. “Combined, we now understand that fatty tissue is an immune and secretory organ and that obesity is an inflammatory immune disease.”
Targeting weight loss leads to less inflammation. “GLP-drugs can now be added to diet and exercise, and the combination of these measures is key to reducing systemic inflammation,” Martin says.
Eingun James Song, MD, FAAD, Co-Chief Medical Officer and Director of Clinical Research at Frontier Dermatology in Seattle, WA, agrees.
“I think with the increasing awareness of cardiometabolic comorbidities in certain diseases like psoriasis, psoriatic arthritis, and hidradenitis suppurativa, it’s just a matter of time before using weight loss medications like GLP-1 / GIP agonists will become a standard of care,” he tells TDD.
“There are studies showing that weight loss with these mechanisms improves various inflammatory markers independent of the weight loss,” he continues, adding that some rheumatologists are already onboard and prescribing them for their patients with tough-to-treat psoriatic arthritis and osteoarthritis.
There are some logistical hurdles to be overcome before this combination becomes a new standard of care. “A lot of payors won’t approve these meds unless it comes from a weight loss physician,” Song says.
