Effects of Semaglutide on Clinical Outcomes and Metabolic Inflammation in Psoriasis (SEMAPSO)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Psoriasis (PsO); Obesity & Overweight; Diabetes Mellitus - Type 2
• Intervention / Treatment: Drug: Semaglutide (Rybelsus®); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jorge Valdespino, MD; Phone Number: +52 8771093680; Email: jorge.valdespino@outlook.com

Study Locations

• Mexico
  • N.L.
    • Monterrey, N.L., Mexico, 64460
      • Recruiting
      • Hospital Universitario Dr. Jose E. Gonzalez
      • Contact: Jorge Valdespino Valdes, MD; Phone Number: +52 8771093680; Email: jorge.valdespino@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Semaglutide group; A total of 31 participants will be randomly assigned to the semaglutide intervention group.	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).
Placebo Comparator: Placebo group; A total of 31 participants will be randomly assigned to the placebo intervention group.	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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of GLP-1 Receptor Agonists on SCD-1 Activity	Change in SCD-1 activity, assessed via acylcarnitine profile (µmol/L), from baseline to Week 12.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving Psoriasis Area and Severity Index (PASI) 75	The proportion of participants achieving a 75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) will be compared between the semaglutide and placebo groups. The Psoriasis Area and Severity Index (PASI) is a validated clinical severity score that ranges from 0 to 72, with higher scores indicating more severe psoriasis. Achievement of PASI 75 represents a clinically meaningful improvement in disease severity.	Weeks 4, 8, and 12
Change in Body Weight	Change in body weight (kilograms) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Fasting Plasma Glucose	Change in fasting plasma glucose (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Total Cholesterol	Change in serum total cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Correlation Between Metabolic Parameters and PASI Improvement	Correlations between PASI improvement and glycemic control (fasting plasma glucose, HbA1c), lipid profile, and anthropometric and hemodynamic parameters (body weight, BMI, waist circumference, hip circumference, waist-to-hip ratio, and blood pressure) will be evaluated overall and by treatment group.	Baseline to Week 12
Change in Dermatology Life Quality Index (DLQI)	Change from baseline to Week 12 in the Dermatology Life Quality Index (DLQI) score will be compared between the semaglutide and placebo groups. The Dermatology Life Quality Index (DLQI) is a validated dermatology-specific quality-of-life questionnaire consisting of 10 items, with total scores ranging from 0 to 30, where higher scores indicate greater impairment in quality of life.	Baseline and Week 12
Correlation Between Psoriasis Severity and Quality of Life Measures	The correlation between psoriasis severity, measured by the Psoriasis Area and Severity Index (PASI), and quality of life, measured by the Dermatology Life Quality Index (DLQI), Patient-Reported Outcomes Measurement Information System 29-Item Profile (PROMIS-29), and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L), will be assessed overall and by treatment group from baseline to Week 12. PASI ranges from 0 to 72, with higher scores indicating more severe psoriasis. DLQI ranges from 0 to 30, with higher scores indicating greater quality-of-life impairment. PROMIS-29 domain scores are reported as T-scores (mean 50, SD 10); higher scores indicate worse symptoms for most domains, except physical function and social roles, where higher scores indicate better functioning. EQ-5D-5L index scores typically range from less than 0 to 1.0, with higher scores indicating better health-related quality of life.	Baseline to Week 12
Change in Serum Interleukin-6 (IL-6)	Change in serum interleukin-6 (IL-6) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Correlation Between PASI and Inflammatory Biomarkers	Correlations between PASI scores and serum levels of IL-6, IL-17, IL-23, TNF-α, CRP, and ESR will be evaluated overall and by treatment group.	Baseline to Week 12
PASI Response by Type 2 Diabetes Status	Improvement in PASI scores and the proportion of participants achieving PASI 75 and PASI 90 will be compared between participants with and without type 2 diabetes mellitus, stratified by treatment group.	Baseline to Week 12
Change in Body Weight in Participants with Type 2 Diabetes	Change in body weight (kg) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline and Week 12
Change in Serum IL-6 by Diabetes Status	Change in serum interleukin-6 (IL-6) levels from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus to evaluate differences in semaglutide-induced inflammatory modulation.	Baseline and Week 12
Correlation Between Baseline Glycemic Control and Change in Psoriasis Severity	The correlation between baseline glycemic control, measured by fasting plasma glucose (mg/dL) and glycated hemoglobin (HbA1c, %), and change in psoriasis severity, measured by the Psoriasis Area and Severity Index (PASI), will be assessed overall and by treatment group from baseline to Week 12. The Psoriasis Area and Severity Index (PASI) ranges from 0 to 72, with higher scores indicating more severe psoriasis.	Baseline to Week 12
Incidence and Type of Adverse Events	Incidence, type, and severity of adverse events associated with semaglutide, reported as number (%) of participants, up to Week 12.	Up to Week 12
Change in Body Mass Index (BMI)	Change in body mass index (BMI, kg/m²) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and week 12
Change in Waist Circumference	Change in waist circumference (centimeters) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Hip Circumference	Change in hip circumference (centimeters) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Waist-to-Hip Ratio	Change in waist-to-hip ratio from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Blood Pressure	Change in systolic and diastolic blood pressure (mmHg) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Time to First Achievement of PASI 75	Time to first achievement of a 75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) will be compared between the semaglutide and placebo groups. The Psoriasis Area and Severity Index (PASI) ranges from 0 to 72, with higher scores indicating more severe psoriasis. Shorter time to PASI 75 represents a better clinical outcome.	Up to Week 12
Change in PROMIS-29 Profile Score	Change from baseline to Week 12 in Patient-Reported Outcomes Measurement Information System 29-Item Profile (PROMIS-29) scores will be compared between the semaglutide and placebo groups. PROMIS-29 is a validated patient-reported outcome instrument that assesses multiple health domains. Domain scores are reported as T-scores standardized to a mean of 50 and a standard deviation of 10. For most domains, higher scores indicate worse symptoms or greater impairment, except for physical function and social roles, where higher scores indicate better functioning.	Baseline and Week 12
Change in EQ-5D-5L Index Score	Change from baseline to Week 12 in the EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) index score will be compared between the semaglutide and placebo groups. The EQ-5D-5L is a standardized instrument for measuring health-related quality of life. Index scores typically range from less than 0 (health states worse than death) to 1.0, where higher scores indicate better health status.	Baseline and Week 12
Change in Serum Interleukin-17 (IL-17)	Change in serum interleukin-17 (IL-17) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Serum Interleukin-23 (IL-23)	Change in serum interleukin-23 (IL-23) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Serum Tumor Necrosis Factor-Alpha (TNF-α)	Change in serum tumor necrosis factor-alpha (TNF-α) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Serum C-Reactive Protein (CRP)	Change in serum C-reactive protein (CRP) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Change in Erythrocyte Sedimentation Rate (ESR)	Change in erythrocyte sedimentation rate (ESR) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline and Week 12
Correlation Between Baseline Glycemic Control and Change in Metabolic Parameters	The correlation between baseline glycemic control, measured by fasting plasma glucose (mg/dL) and glycated hemoglobin (HbA1c, %), and changes in metabolic parameters, including body weight (kg), body mass index (kg/m²), and serum acylcarnitine profile, will be assessed overall and by treatment group from baseline to Week 12.	Baseline to Week 12
Change in Body Mass Index (BMI) by Diabetes Status	Change in body mass index (BMI, kg/m²) from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.	Baseline and Week 12
Change in Acylcarnitine Profile by Diabetes Status	Change in serum acylcarnitine profile from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.	Baseline and Week 12
Change in Serum IL-17 by Diabetes Status	Change in serum interleukin-17 (IL-17) levels from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.	Baseline and Week 12
Change in Serum IL-23 by Diabetes Status	Change in serum interleukin-23 (IL-23) levels from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.	Baseline and Week 12
Change in Serum TNF-α by Diabetes Status	Change in serum tumor necrosis factor-alpha (TNF-α) levels from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.	Baseline and Week 12
Change in Serum CRP by Diabetes Status	Change in serum C-reactive protein (CRP) levels from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.	Baseline and Week 12
Change in ESR by Diabetes Status	Change in erythrocyte sedimentation rate (ESR) from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.	Baseline and Week 12
Change in HbA1c	Change in glycated hemoglobin (HbA1c, %) from baseline to Week 12.	Baseline to Week 12
Change in HDL Cholesterol	Change in HDL cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline to Week 12
Change in LDL Cholesterol	Change in LDL cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline to Week 12
Change in VLDL Cholesterol	Change in VLDL cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline to Week 12
Change in Triglycerides	Change in triglycerides (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.	Baseline to Week 12
Change in Body Weight in Participants without Type 2 Diabetes	Change in body weight (kg) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12
Change in Body Mass Index (BMI) in Participants with Type 2 Diabetes	Change in BMI (kg/m²) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline to Week 12
Change in Body Mass Index (BMI) in Participants without Type 2 Diabetes	Change in BMI (kg/m²) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum IL-6 in Participants with Type 2 Diabetes	Change in serum interleukin-6 (IL-6, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum IL-6 in Participants without Type 2 Diabetes	Change in serum interleukin-6 (IL-6, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum IL-17 in Participants without Type 2 Diabetes	Change in serum interleukin-17 (IL-17, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum IL-17 in Participants with Type 2 Diabetes	Change in serum interleukin-17 (IL-17, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum IL-23 in Participants with Type 2 Diabetes	Change in serum interleukin-23 (IL-23, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum IL-23 in Participants without Type 2 Diabetes	Change in serum interleukin-23 (IL-23, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum TNF-α in Participants with Type 2 Diabetes	Change in serum tumor necrosis factor-alpha (TNF-α, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum TNF-α in Participants without Type 2 Diabetes	Change in serum tumor necrosis factor-alpha (TNF-α, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum C-Reactive Protein (CRP) in Participants with Type 2 Diabetes	Change in serum C-reactive protein (CRP, mg/L) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline to Week 12
Change in Serum C-Reactive Protein (CRP) in Participants without Type 2 Diabetes	Change in serum C-reactive protein (CRP, mg/L) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12
Change in Erythrocyte Sedimentation Rate (ESR) in Participants with Type 2 Diabetes	Change in erythrocyte sedimentation rate (ESR, mm/h) from baseline to Week 12 in participants with type 2 diabetes mellitus.	Baseline to Week 12
Change in Erythrocyte Sedimentation Rate (ESR) in Participants without Type 2 Diabetes	Change in erythrocyte sedimentation rate (ESR, mm/h) from baseline to Week 12 in participants without type 2 diabetes mellitus.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: February 3, 2026
• First Posted (Actual): February 11, 2026

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: diabetes; GLP-1; obesity; overweight; semaglutide; dermatology; clinical trial; psoriasis
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Skin Diseases, Papulosquamous; Skin Diseases; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2; Diabetes Mellitus; Psoriasis; semaglutide
• Other Study ID Numbers: DE26-00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No