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NCT Number: NCT07401992

Effects of Semaglutide on Clinical Outcomes and Metabolic Inflammation in Psoriasis

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.

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Key information

Conditions

Psoriasis (PsO) Body Weight Diabetes Mellitus Diabetes Mellitus - Type 2 Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity & Overweight Overnutrition Overweight Pathological Conditions, Signs and Symptoms Psoriasis Signs and Symptoms Skin Diseases Skin Diseases, Papulosquamous Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Hospital Universitario Dr. José E. González

Monterrey, N.L., 64460, Mexico

Location status: Recruiting

Location contact

Jorge Valdespino Valdes, MD

CONTACT

[email protected]

+52 8771093680

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Semaglutide (Rybelsus®)

Drug

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

Drug

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 outcomes

  1. Effect of GLP-1 Receptor Agonists on SCD-1 Activity

    Time frame: Baseline to Week 12

    Change in SCD-1 activity, assessed via acylcarnitine profile (µmol/L), from baseline to Week 12.

Secondary outcomes

  1. Proportion of Participants Achieving Psoriasis Area and Severity Index (PASI) 75

    Time frame: Weeks 4, 8, and 12

    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.

  2. Change in Body Weight

    Time frame: Baseline and Week 12

    Change in body weight (kilograms) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  3. Change in Fasting Plasma Glucose

    Time frame: Baseline and Week 12

    Change in fasting plasma glucose (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  4. Change in Total Cholesterol

    Time frame: Baseline and Week 12

    Change in serum total cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  5. Correlation Between Metabolic Parameters and PASI Improvement

    Time frame: Baseline to Week 12

    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.

  6. Change in Dermatology Life Quality Index (DLQI)

    Time frame: Baseline and Week 12

    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.

  7. Correlation Between Psoriasis Severity and Quality of Life Measures

    Time frame: Baseline to Week 12

    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.

  8. Change in Serum Interleukin-6 (IL-6)

    Time frame: Baseline and Week 12

    Change in serum interleukin-6 (IL-6) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  9. Correlation Between PASI and Inflammatory Biomarkers

    Time frame: Baseline to Week 12

    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.

  10. PASI Response by Type 2 Diabetes Status

    Time frame: Baseline to Week 12

    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.

  11. Change in Body Weight in Participants with Type 2 Diabetes

    Time frame: Baseline and Week 12

    Change in body weight (kg) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  12. Change in Serum IL-6 by Diabetes Status

    Time frame: Baseline and Week 12

    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.

  13. Correlation Between Baseline Glycemic Control and Change in Psoriasis Severity

    Time frame: Baseline to Week 12

    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.

  14. Incidence and Type of Adverse Events

    Time frame: Up to Week 12

    Incidence, type, and severity of adverse events associated with semaglutide, reported as number (%) of participants, up to Week 12.

  15. Change in Body Mass Index (BMI)

    Time frame: Baseline and week 12

    Change in body mass index (BMI, kg/m²) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  16. Change in Waist Circumference

    Time frame: Baseline and Week 12

    Change in waist circumference (centimeters) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  17. Change in Hip Circumference

    Time frame: Baseline and Week 12

    Change in hip circumference (centimeters) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  18. Change in Waist-to-Hip Ratio

    Time frame: Baseline and Week 12

    Change in waist-to-hip ratio from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  19. Change in Blood Pressure

    Time frame: Baseline and Week 12

    Change in systolic and diastolic blood pressure (mmHg) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  20. Time to First Achievement of PASI 75

    Time frame: Up to Week 12

    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.

  21. Change in PROMIS-29 Profile Score

    Time frame: Baseline and Week 12

    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.

  22. Change in EQ-5D-5L Index Score

    Time frame: Baseline and Week 12

    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.

  23. Change in Serum Interleukin-17 (IL-17)

    Time frame: Baseline and Week 12

    Change in serum interleukin-17 (IL-17) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  24. Change in Serum Interleukin-23 (IL-23)

    Time frame: Baseline and Week 12

    Change in serum interleukin-23 (IL-23) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  25. Change in Serum Tumor Necrosis Factor-Alpha (TNF-α)

    Time frame: Baseline and Week 12

    Change in serum tumor necrosis factor-alpha (TNF-α) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  26. Change in Serum C-Reactive Protein (CRP)

    Time frame: Baseline and Week 12

    Change in serum C-reactive protein (CRP) levels from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  27. Change in Erythrocyte Sedimentation Rate (ESR)

    Time frame: Baseline and Week 12

    Change in erythrocyte sedimentation rate (ESR) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  28. Correlation Between Baseline Glycemic Control and Change in Metabolic Parameters

    Time frame: Baseline to Week 12

    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.

  29. Change in Body Mass Index (BMI) by Diabetes Status

    Time frame: Baseline and Week 12

    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.

  30. Change in Acylcarnitine Profile by Diabetes Status

    Time frame: Baseline and Week 12

    Change in serum acylcarnitine profile from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.

  31. Change in Serum IL-17 by Diabetes Status

    Time frame: Baseline and Week 12

    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.

  32. Change in Serum IL-23 by Diabetes Status

    Time frame: Baseline and Week 12

    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.

  33. Change in Serum TNF-α by Diabetes Status

    Time frame: Baseline and Week 12

    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.

  34. Change in Serum CRP by Diabetes Status

    Time frame: Baseline and Week 12

    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.

  35. Change in ESR by Diabetes Status

    Time frame: Baseline and Week 12

    Change in erythrocyte sedimentation rate (ESR) from baseline to Week 12 will be compared between participants with and without type 2 diabetes mellitus.

  36. Change in HbA1c

    Time frame: Baseline to Week 12

    Change in glycated hemoglobin (HbA1c, %) from baseline to Week 12.

  37. Change in HDL Cholesterol

    Time frame: Baseline to Week 12

    Change in HDL cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  38. Change in LDL Cholesterol

    Time frame: Baseline to Week 12

    Change in LDL cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  39. Change in VLDL Cholesterol

    Time frame: Baseline to Week 12

    Change in VLDL cholesterol (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  40. Change in Triglycerides

    Time frame: Baseline to Week 12

    Change in triglycerides (mg/dL) from baseline to Week 12 will be compared between the semaglutide and placebo groups.

  41. Change in Body Weight in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in body weight (kg) from baseline to Week 12 in participants without type 2 diabetes mellitus.

  42. Change in Body Mass Index (BMI) in Participants with Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in BMI (kg/m²) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  43. Change in Body Mass Index (BMI) in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in BMI (kg/m²) from baseline to Week 12 in participants without type 2 diabetes mellitus.

  44. Change in Serum IL-6 in Participants with Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum interleukin-6 (IL-6, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  45. Change in Serum IL-6 in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum interleukin-6 (IL-6, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.

  46. Change in Serum IL-17 in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum interleukin-17 (IL-17, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.

  47. Change in Serum IL-17 in Participants with Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum interleukin-17 (IL-17, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  48. Change in Serum IL-23 in Participants with Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum interleukin-23 (IL-23, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  49. Change in Serum IL-23 in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum interleukin-23 (IL-23, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.

  50. Change in Serum TNF-α in Participants with Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum tumor necrosis factor-alpha (TNF-α, pg/mL) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  51. Change in Serum TNF-α in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum tumor necrosis factor-alpha (TNF-α, pg/mL) from baseline to Week 12 in participants without type 2 diabetes mellitus.

  52. Change in Serum C-Reactive Protein (CRP) in Participants with Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum C-reactive protein (CRP, mg/L) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  53. Change in Serum C-Reactive Protein (CRP) in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in serum C-reactive protein (CRP, mg/L) from baseline to Week 12 in participants without type 2 diabetes mellitus.

  54. Change in Erythrocyte Sedimentation Rate (ESR) in Participants with Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in erythrocyte sedimentation rate (ESR, mm/h) from baseline to Week 12 in participants with type 2 diabetes mellitus.

  55. Change in Erythrocyte Sedimentation Rate (ESR) in Participants without Type 2 Diabetes

    Time frame: Baseline to Week 12

    Change in erythrocyte sedimentation rate (ESR, mm/h) from baseline to Week 12 in participants without type 2 diabetes mellitus.

Study contacts

Contact information is provided by the study sponsor or research team.

Jorge Valdespino, MD

CONTACT

[email protected]

+52 8771093680

Sponsors and collaborators

Lead sponsor

Hospital Universitario Dr. Jose E. Gonzalez

Other

Registry information

Official study title

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

Acronym: SEMAPSO

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Feb 11, 2026
Registry last updated
Feb 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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