Effects of Semaglutide on Clinical Outcomes and Metabolic Inflammation in Psoriasis

Official title

Effects of Semaglutide on Clinical Outcomes and Metabolic Inflammation in Psoriasis: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial

Overview

This study will evaluate the effects of oral semaglutide in combination with topical corticosteroid/calcipotriol on clinical outcomes and metabolic inflammation in patients with plaque psoriasis and overweight/obesity and/or type 2 diabetes mellitus. A total of 62 participants will be randomized to receive either semaglutide plus topical corticosteroid/calcipotriol or placebo plus topical corticosteroid/calcipotriol for 12 weeks. Clinical efficacy will be assessed using the Psoriasis Area and Severity Index (PASI), and quality of life will be evaluated using DLQI, PROMIS-29, and EQ-5D-5L. Systemic inflammatory markers will also be measured to assess metabolic inflammation.

Detailed description

Psoriasis is a chronic inflammatory skin disease frequently associated with metabolic comorbidities, including obesity and type 2 diabetes mellitus. Increasing evidence suggests that systemic metabolic inflammation may contribute to psoriasis severity and treatment response. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely used in the management of type 2 diabetes and obesity, has demonstrated anti-inflammatory effects that may be relevant to psoriasis.

This study is a randomized, triple-blind, placebo-controlled clinical trial designed to evaluate the effects of oral semaglutide on clinical disease activity, quality of life, and metabolic inflammatory markers in patients with plaque psoriasis and overweight/obesity and/or type 2 diabetes mellitus.

A total of 62 participants will be enrolled and randomized in a 1:1 ratio to one of two treatment groups. One group will receive oral semaglutide in combination with topical corticosteroid/calcipotriol cream, while the comparator group will receive oral placebo in combination with topical corticosteroid/calcipotriol cream. All participants will receive treatment for 12 weeks.

Clinical assessments will be performed at baseline and at weeks 4, 8, and 12. Disease severity and clinical response will be evaluated using the Psoriasis Area and Severity Index (PASI) at each visit. Patient-reported quality of life will be assessed using the Dermatology Life Quality Index (DLQI), the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at baseline and at week 12.

Blood samples will be collected at baseline and at week 12 to evaluate systemic inflammatory and metabolic biomarkers, allowing assessment of changes in metabolic inflammation associated with treatment.

The primary hypothesis is that participants receiving semaglutide in combination with topical corticosteroid/calcipotriol will demonstrate greater improvement in clinical severity and inflammatory markers compared with those receiving placebo plus topical corticosteroid/calcipotriol. Findings from this study may provide evidence supporting the role of metabolic-targeted therapies as adjunctive treatment in psoriasis patients with metabolic comorbidities.

Interventions

• Drug Semaglutide (Rybelsus®)
  Oral semaglutide will be administered once daily at a dose of 3 mg for the first 4 weeks, followed by 7 mg once daily for the next 4 weeks, and 14 mg once daily for the final 4 weeks (total treatment duration: 12 weeks). All participants will also receive conventional topical therapy for 12 weeks, consisting of a topical corticosteroid and a vitamin D analog (calcipotriol).
• Drug Placebo
  A total of 31 participants will be randomly assigned to the placebo intervention group. They will receive a daily placebo tablet containing starch for 12 weeks. All participants will also receive conventional topical therapy for 12 weeks, consisting of a topical corticosteroid and a vitamin D analog (calcipotriol).

Primary outcome measures

• Effect of GLP-1 Receptor Agonists on SCD-1 Activity [Time frame: Baseline to Week 12]

Secondary outcome measures (12)

• Proportion of Participants Achieving Psoriasis Area and Severity Index (PASI) 75 [Time frame: Weeks 4, 8, and 12]
• Change in Body Weight [Time frame: Baseline and Week 12]
• Change in Fasting Plasma Glucose [Time frame: Baseline and Week 12]
• Change in Total Cholesterol [Time frame: Baseline and Week 12]
• Correlation Between Metabolic Parameters and PASI Improvement [Time frame: Baseline to Week 12]
• Change in Dermatology Life Quality Index (DLQI) [Time frame: Baseline and Week 12]
• Correlation Between Psoriasis Severity and Quality of Life Measures [Time frame: Baseline to Week 12]
• Change in Serum Interleukin-6 (IL-6) [Time frame: Baseline and Week 12]
• Correlation Between PASI and Inflammatory Biomarkers [Time frame: Baseline to Week 12]
• PASI Response by Type 2 Diabetes Status [Time frame: Baseline to Week 12]
• Change in Body Weight in Participants with Type 2 Diabetes [Time frame: Baseline and Week 12]
• Change in Serum IL-6 by Diabetes Status [Time frame: Baseline and Week 12]

Eligibility criteria

Inclusion criteria

• Male or female participants aged ≥18 years at the time of randomization.
• Clinical diagnosis of plaque psoriasis with Psoriasis Area and Severity Index (PASI) ≥3 and body surface area (BSA) ≥3%.
• Body mass index (BMI) ≥25 kg/m², consistent with overweight or obesity.
• Participants with or without type 2 diabetes mellitus.
• Participants with diabetes must be on stable antidiabetic therapy (no changes in medication or dosage within the previous 3 months) and have adequate glycemic control, defined as HbA1c ≤9.0% at baseline.
• No use of systemic psoriasis therapies (e.g., methotrexate, cyclosporine) for at least 8 weeks prior to randomization.
• No use of biologic therapies for at least 3 months prior to randomization.

Exclusion criteria

• Diagnosis of a non-plaque psoriasis subtype, including pustular, guttate, nail, inverse, psoriatic arthritis, or erythrodermic psoriasis.
• Pregnancy or breastfeeding at the time of screening or enrollment.
• Insulin-dependent diabetes mellitus or current use of sulfonylureas.
• Active malignancy at the time of screening.
• History of thyroid neoplasia.
• Presence of autoimmune diseases.
• Use of systemic therapies within 8 weeks prior to randomization.
• Use of biologic therapies within 3 months prior to randomization.
• Renal insufficiency.
• Heart failure.
• Hepatic insufficiency.
• History of pancreatitis.
• Current treatment with other GLP-1 receptor agonists.
• History of inflammatory bowel disease.
• Known allergy to starch.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Mexico · 1 center

• Hospital Universitario Dr. José E. González — Monterrey

Identifiers

NCT: NCT07401992 · DE26-00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗