INTRODUCTION
The glucagon-like peptide-1 receptor agonists (GLP1RAs) are a widely popularized drug class due to their notable success in promoting weight loss. The GLP1RAs, dulaglutide, exenatide, semaglutide, liraglutide, tirzepatide, and lixisenatide are FDAapproved for use in the treatment of obesity and type 2 diabetes mellitus (DM), particularly to reduce cardiovascular risk and improve glycemic control.1,2,3 GLP1RAs work by mimicking glucagon-like peptide-1 (GLP-1), an incretin, that functions to subdue appetite, delay gastric emptying, and regulate homeostasis of glucose. GLP1RAs also have anti-inflammatory effects; GLP-1 receptors are expressed in activated regulatory T cells and GLP-1 receptor agonists reduce proinflammatory cytokines through inhibition of tumor necrosis factor alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin (IL)-23, IL-17, and IL-22.1
Despite their popular use in bariatrics, cardiology, and endocrinology, GLP1RAs should not be overlooked by dermatologists. While mounting evidence has shown the utility of GLP1RAs in the treatment of psoriasis, they have also proved useful in treating hidradenitis suppurativa (HS), acanthosis nigricans, Hailey-Hailey disease, and diabetic wounds. Additionally, dermatologists should be aware of lipo-cutaneous adverse reactions, as well as the dermatologic manifestations of rapid weight loss in patients using GLP1RAs.
Psoriasis
The anti-inflammatory effects of GLP1RAs have most extensively been used in the treatment of psoriasis, a prominently IL-17, IL-23-, and TNF-α-mediated condition. Reduction in psoriasis symptoms has been observed in patients taking GLP1RAs, and as an added benefit, these drugs simultaneously address comorbid obesity and DM.4,5
A recent meta-analysis including 63 patients who received liraglutide or exenatide subcutaneously revealed significant reductions in Psoriasis Area Severity Index (PASI) after treatment in patients with psoriasis alone (P=0.002) and in patients with psoriasis and comorbid DM (P=0.005). Overall, over one-third (35%) of patients showed 75% improvement in PASI from baseline after 6-12 weeks of treatment.4 This study drew from results of a randomized-controlled trial (RCT) including 25 patients with psoriasis and DM taking liraglutide that showed improvements in PASI, Dermatology Life Quality Index (DLQI) (P<0.05), weight (P<0.001), body mass index (BMI) (P<0.001), and fasting blood glucose (P<0.001). In this RCT, the most common adverse events in the treatment group were nausea or vomiting (54.55%), and no serious adverse events occurred.5 Notably, one case study has reported worsening of psoriatic lesions after two weeks of treatment with liraglutide, thought to be due to a cytokine imbalance.6 These studies demonstrate current evidence for the efficacy of GLP1RAs in a multimodal treatment approach for patients with psoriasis and metabolic comorbidities, achieved through the drug’s anti-inflammatory effects and promotion of weight loss and normoglycemia.
Hidradenitis Suppurativa
HS has well-established associations with metabolic syndrome and obesity, as weight gain not only predisposes to HS but exacerbates it.1,7 Systemic inflammation in HS is modulated in part by IL-17, TNF-α, and NF-κB, targets of GLP1RAs. A recently published prospective cohort study including 14 patients with HS demonstrated that treatment with liraglutide led to significant decreases in BMI (P=0.0002), waist circumference (P=0.01), C-reactive protein (P=0.04), and homocysteine (P=0.005). Improvements in Hurley stage (P=0.002) and DLQI (P=0.04) were also observed.8 While further evidence is warranted, the use of GLP1RAs as an adjunctive therapy in patients with HS and elevated BMIs can be considered.
Additional Applications in Dermatologic Conditions
Case-based evidence exists highlighting the use of GLP1RAs for a variety of dermatologic conditions. One report demonstrated the use of liraglutide in achieving improvements in the clinical appearance of acanthosis nigricans.9 Hailey-Hailey disease, a genodermatosis with increased expression of IL-17, was successfully treated with liraglutide over a six-month period in one case of a previously treatment-refractory patient.10 Additionally, in vitro and in vivo studies of liraglutide and exenatide, respectively, have shown efficacy in accelerating wound healing in DM patients.11,12
Despite their popular use in bariatrics, cardiology, and endocrinology, GLP1RAs should not be overlooked by dermatologists. While mounting evidence has shown the utility of GLP1RAs in the treatment of psoriasis, they have also proved useful in treating hidradenitis suppurativa (HS), acanthosis nigricans, Hailey-Hailey disease, and diabetic wounds. Additionally, dermatologists should be aware of lipo-cutaneous adverse reactions, as well as the dermatologic manifestations of rapid weight loss in patients using GLP1RAs.
Psoriasis
The anti-inflammatory effects of GLP1RAs have most extensively been used in the treatment of psoriasis, a prominently IL-17, IL-23-, and TNF-α-mediated condition. Reduction in psoriasis symptoms has been observed in patients taking GLP1RAs, and as an added benefit, these drugs simultaneously address comorbid obesity and DM.4,5
A recent meta-analysis including 63 patients who received liraglutide or exenatide subcutaneously revealed significant reductions in Psoriasis Area Severity Index (PASI) after treatment in patients with psoriasis alone (P=0.002) and in patients with psoriasis and comorbid DM (P=0.005). Overall, over one-third (35%) of patients showed 75% improvement in PASI from baseline after 6-12 weeks of treatment.4 This study drew from results of a randomized-controlled trial (RCT) including 25 patients with psoriasis and DM taking liraglutide that showed improvements in PASI, Dermatology Life Quality Index (DLQI) (P<0.05), weight (P<0.001), body mass index (BMI) (P<0.001), and fasting blood glucose (P<0.001). In this RCT, the most common adverse events in the treatment group were nausea or vomiting (54.55%), and no serious adverse events occurred.5 Notably, one case study has reported worsening of psoriatic lesions after two weeks of treatment with liraglutide, thought to be due to a cytokine imbalance.6 These studies demonstrate current evidence for the efficacy of GLP1RAs in a multimodal treatment approach for patients with psoriasis and metabolic comorbidities, achieved through the drug’s anti-inflammatory effects and promotion of weight loss and normoglycemia.
Hidradenitis Suppurativa
HS has well-established associations with metabolic syndrome and obesity, as weight gain not only predisposes to HS but exacerbates it.1,7 Systemic inflammation in HS is modulated in part by IL-17, TNF-α, and NF-κB, targets of GLP1RAs. A recently published prospective cohort study including 14 patients with HS demonstrated that treatment with liraglutide led to significant decreases in BMI (P=0.0002), waist circumference (P=0.01), C-reactive protein (P=0.04), and homocysteine (P=0.005). Improvements in Hurley stage (P=0.002) and DLQI (P=0.04) were also observed.8 While further evidence is warranted, the use of GLP1RAs as an adjunctive therapy in patients with HS and elevated BMIs can be considered.
Additional Applications in Dermatologic Conditions
Case-based evidence exists highlighting the use of GLP1RAs for a variety of dermatologic conditions. One report demonstrated the use of liraglutide in achieving improvements in the clinical appearance of acanthosis nigricans.9 Hailey-Hailey disease, a genodermatosis with increased expression of IL-17, was successfully treated with liraglutide over a six-month period in one case of a previously treatment-refractory patient.10 Additionally, in vitro and in vivo studies of liraglutide and exenatide, respectively, have shown efficacy in accelerating wound healing in DM patients.11,12
