Glucagon-Like Peptide-1 Receptor Agonist Therapy Is Associated With Improvement in Psoriatic Arthritis–Related and Metabolic Outcomes: A Retrospective Analysis of Two Cohorts

Abstract

Objective.

Obesity is highly prevalent in psoriatic arthritis (PsA) and is associated with worse disease outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly being used for weight loss and diabetes, but their impact on PsA outcomes remains unclear. We aimed to characterize patients with PsA initiating GLP-1RAs and assess longitudinal changes in weight, PsA activity, and cardiometabolic parameters.

Methods.

We conducted a retrospective analysis of patients with PsA who initiated GLP-1RAs. PsA disease activity data and cardiometabolic parameters from clinical visits within one year before and after GLP-1RA initiation, along with demographics and comorbidities, were collected.

Results.

Forty-eight patients with a median body mass index of 34.9 were included. Significant weight loss was observed posttreatment (−6.43 kg, 95% confidence interval [CI] −9.5 to −2.0; P < 0.0001), with 60% losing ≥5% of their baseline bodyweight. C-reactive protein levels (−1.1 mg/L; P = 0.002), pain scores (−1.0; P = 0.01), and triglyceride levels (−0.35 mmol/L; P = 0.02) decreased significantly. Each 1% reduction in body weight was associated with significant improvements in the Disease Activity in Psoriatic Arthritis score (β = −0.49, 95% CI −0.94 to −0.03), tender joint count (β = −0.18, 95% CI −0.32 to −0.05), EuroQol 5-domain (β = 0.0016, 95% CI 0.008–0.023), low-density lipoprotein cholesterol levels (β = −0.05, 95% CI −0.10 to −0.003), and systolic blood pressure (β = −0.67, 95% CI −1.18 to −0.15).

Conclusion.

In this real-world study, GLP-1RA therapy in PsA was associated with clinically meaningful weight loss and improvements in systemic inflammation, pain, and cardiometabolic markers. Improvements in psoriatic outcomes were proportional to the degree of weight loss. These findings warrant further investigation in prospective controlled studies to evaluate the role of GLP-1RAs in PsA management and comorbidities.

INTRODUCTION

Increased weight and obesity represent a significant burden on patients with psoriatic arthritis (PsA), affecting up to 80% of patients.¹ Obesity, a chronic, progressive, relapsing disorder of excess adipose tissue that impairs health, is particularly relevant in psoriatic disease (PsD), in which heightened adiposity can act as a risk (and possible causal) factor and amplifier of disease.² In addition to common underlying inflammatory etiologies of PsA and obesity, this relationship is evidenced clinically. Patients who are overweight and with obesity are at increased risk of developing psoriasis and PsA, have worse disease outcomes, and have decreased response to treatment.³

Weight loss, mostly through lifestyle modifications such as diet and exercise, has been shown to be an effective intervention in PsA, but they often lead to a modest reduction in weight loss that is difficult to maintain long-term.⁴ Although bariatric surgery can lead to clinically relevant long-term weight loss, surgical complications limit more widespread use. Glucagon-like peptide-1 receptors agonists (GLP-1RAs; this includes combined GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists) have emerged as highly effective weight loss therapies with a multitude of clinical benefits, including improvement in cardiovascular disease, stroke, and diabetes, as well as efficacy in other arthritic conditions, such as osteoarthritis.⁵

Limited data in PsD have shown that GLP-1RAs may improve outcomes, especially psoriatic skin activity.⁶ Although this may be due to weight loss alone, mechanistic studies point to possible direct anti-inflammatory and immunoregulatory effects of GLP-1RAs.^7–10 Overall, the lack of data on the unique impact and usage of GLP-1RAs in PsD remains a gap in the field. In this retrospective study nested in two prospectively observed cohorts, we aimed to characterize patients with PsA initiating GLP-1RAs and to assess longitudinal changes in weight, PsD activity, and cardiometabolic parameters.

METHODS

Population and setting.

Two prospective, observational cohorts were analyzed in this study. The University of Toronto PsA (Toronto) cohort at Women’s College Hospital has been collecting data since 2016 and is comprised of 766 patients with PsD who are observed prospectively every 3 to 12 months. The New York University (NYU) Langone Health Psoriatic Arthritis Center (NYU PAC) cohort has followed patients prospectively at every clinic visit since 2016, and it includes 1,134 patients with PsA. From these cohorts, patients with PsA were included if they (1) were started on US Food and Drug Administration/Health Canada–approved GLP-1RAs for weight loss or diabetes and (2) were seen at the Toronto or NYU cohort within one year before and after medication implementation. GLP-1RA selection and titration was done by the participant’s rheumatologist, primary care doctor, endocrinologist, cardiologist, or weight management specialist. Except for the medications prescribed by the rheumatologist, the research teams did not have input on medication selection or titration. This study was approved by the NYU Institutional Review Board (s-20–00084) and the Women’s College Hospital Research Ethics Board (2025–0026-E), with waived written consent from individual participants because all data were collected in a deidentified manner.

Outcomes.

Patient baseline and longitudinal characteristics were assessed at the visit closest to the initiation of GLP-1RA within one year and at a second visit within one year after GLP-1RA initiation (closest to six months). Comorbid conditions, metabolic parameters, PsA disease activity measures, and patient-reported outcomes were extracted from the cohort databases. Metabolic parameters include weight and body mass index (BMI), lipid profile, blood pressure, and liver enzymes. PsA-related measures included the Disease Activity in Psoriatic Arthritis (DAPSA) score, tender and swollen joint count, percent of body surface area covered by psoriasis, and C-reactive protein (CRP) levels. Patient-reported outcomes included patient-reported pain and global scores (scored from 0–10, with 10 representing the worst pain and overall health assessment), Functional Assessment of Chronic Illness Therapy–Fatigue scale to measure fatigue, Health Assessment Questionnaire–Disability Index (HAQ-DI) to measure function, and EuroQol 5-domain (EQ-5D) to measure quality of life.

Statistical analysis.

Summary statistics were presented as frequencies (percentages) and median and interquartile range (IQR), as appropriate. Within-patient changes in the above variables before and after GLP-1RA treatment were assessed using the Wilcoxon signed-rank test and between group changes were assessed with Mann-Whitney U tests. Linear regression models, adjusting for baseline outcome values, were used to examine the associations between percent weight change and change in outcomes.

Data availability.

Data are available upon request to the authors.

RESULTS

A total of 48 patients were identified who met the inclusion criteria from 2019 to 2025, comprising 18 patients from the Toronto cohort and 30 patients from the NYU PAC cohort. Thirty-six patients were receiving semaglutide, and 12 were receiving tirzepatide. GLP-1RAs were primarily prescribed for a primary indication of obesity (72.9%) by primary care physicians (43.8%) and endocrinologists (22.9%; Supplementary Table 1). Those who were started on GLP-1RAs were 52.7 years, 60.4% were women, and they had an average BMI of 34.9 at their visit before GLP-1RA initiation (Table 1). The baseline visit was a median of 80 days before GLP-1RA initiation. At baseline, 33.3% of patients were taking conventional disease-modifying antirheumatic drugs (DMARDs), and 77.1% were taking biologic or targeted synthetic DMARDs for PsA. The median baseline DAPSA score was 14.5 (IQR 9.5–18.9), tender joint count was 1 (IQR 0–3.8), swollen joint count was 0 (IQR 0–1), pain score was 5 (IQR 2.4–7), patient global score was 6 (IQR 3.1–7), physician global score was 2 (IQR 1–3), HAQ-DI score was 0.72 (IQR 0.3 to −1.25), CRP level was 3.7 mg/L (IQR 1.9–11), and the percent body surface area covered by psoriasis was 0 (IQR 0–1). In terms of comorbidities, 81% had obesity, 19% were overweight, 35% had diabetes mellitus, 50% had hypertension, 21% had metabolic dysfunction–associated steatotic liver disease, 40% had depression, 13% had cardiovascular disease, 35% had sleep apnea, and 27% had osteoarthritis.

Table 1.

Baseline patient characteristics^*

Characteristic	Value	N
Demographics
Age, median, years	52.7	48
Female sex, n (%)	29 (60.4)	48
GLP-1 medication initiated, n (%)
Semaglutide	36 (75)	48
Tirzepatide	12 (25)	48
Baseline psoriatic arthritis treatment, n (%)
csDMARD	16 (33.3)	48
b/tsDMARD	37 (77.1)	48
TNF inhibitor	12 (27.1)	48
IL-17 inhibitor	15 (31.1)	48
IL-23 inhibitor	2 (4.2)	48
JAK inhibitor	3 (6.3)	48
Psoriatic disease activity measures, median (IQR)
DAPSA score	14.5 (9.5–18.9)	26
CRP, mg/L	3.7 (1.9–11)	38
Tender joint count	1 (0–3.8)	68
Swollen joint count	0 (0–1)	66
Pain score	5 (2.4–7)	29
Patient global score	6 (3.1–7)	26
Physician global score	2 (1–3)	35
HAQ-DI	0.72 (0.30–1.25)	18
FACIT-Fatigue score	33.1 (22.9–40.75)	18
EQ-5D index	0.61 (0.57–0.78)	18
Psoriasis body surface area, %	0.0 (0.0–1.0)	45
Comorbidities, n (%)
Overweighta	9 (18.8)	48
Obesityb	39 (81.3)	48
Diabetes mellitus	17 (35.4)	48
Hypertension	24 (50.0)	48
MASLD	10 (20.8)	48
Depression	19 (39.6)	48
Cardiovascular disease	6 (12.5)	48
Sleep apnea	17 (35.4)	48
Osteoarthritis	13 (27.1)	48

Note: Higher scores indicating worse disease activity.

^*Tender and swollen joint counts totaled 0 to 68. Pain score measured 0 to 10, with 10 denoting the worst pain imaginable. Patient global score measured 0 to 10, with 10 denoting the worst health status. Physician global score measured 0 to 10, with 10 representing the worst patient status. HAQ-DI measured from 0 to 3, with 3 denoting worse health status. FACIT-Fatigue score measured 0 to 52, with 52 indicating no fatigue. EQ-5D index measured from 0 to 1, with 1 representing full health. b/tsDMARD, biologic/targeted synthetic disease-modifying antirheumatic drug; CRP, C-reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DAPSA, Disease Activity in Psoriatic Arthritis; EQ-5D, EuroQol 5-domain; FACIT, Functional Assessment of Chronic Illness Therapy; GLP-1, glucagon-like peptide-1; HAQ-DI, Health Assessment Questionnaire–Disability Index; IL-17, interleukin-17; IL-23, interleukin-23; IQR, interquartile range; MASLD, metabolic dysfunction–associated steatotic liver disease; TNF tumor necrosis factor.

^aOverweight defined as body mass index 25 to 29.9.

^bObesity defined as body mass index ≥30.

At the clinic visit that was within one year following initiation of GLP-1RA (208 days, IQR 157–250), median weight loss was 6.43 kg (IQR −9.5 to −2). Of the 48 patients who were started on GLP-1RAs, 44 (91.7%) were still taking the medication at the time of follow-up, with discontinuations due to insurance coverage or side effects (Supplementary Table 1). A total of 20.8% of patients had no change or an increase in body weight, 18.5% of patients had a 1% to 4.9% body weight reduction, 35.4% of patients had a 5% to 9.9% body weight reduction, and 25% of patients had ≥10% body weight reduction. Triglyceride levels (−13.5 mg/dL, IQR −27.5 to −5; P = 0.02), CRP levels (−1.1 mg/L, IQR −2 to −0.2; P = 0.002), swollen joint count (0, IQR 0–0; P = 0.03), and pain levels (−1, IQR −1.75 to 0; P = 0.01) were all significantly lower in patients after GLP-1RA administration (Table 2). Numerical yet nonsignificant improvement was seen in the DAPSA score; tender joint count; patient global score; function, fatigue, and quality of life; cholesterol levels; and alanine transaminase levels. As a sensitivity analysis, we also looked at patients who had no changes to their PsA medications during the follow-up time period (n = 40). In this subset, median weight loss was 6.13 kg (IQR −9.9 to −0.48); pain score (−1.0, IQR −2 to 0.3; P = 0.011) and CRP levels (−1.5 mg/dL, IQR −6.0 to 0.2; P = 0.005) continued to have statistically significant improvement (Supplementary Table 2).

Table 2.

Longitudinal changes in cardiometabolic and psoriatic arthritis outcomes in patients initiated on glucagon-like peptide-1^*

Outcome	Median change (IQR)	P value	N
Cardiometabolic
Total cholesterol, mg/dL	−8.9 (−17.4 to 7.7)	0.10	28
Triglyceride, mg/dL	−13.5 (−27.5 to −5)	0.02	28
High-density lipoprotein, mg/dL	3 (−3.4 to 6.5)	0.13	28
Low-density lipoprotein, mg/dL	1 (−16.9 to 6.5)	0.49	28
Creatinine, mg/dL	−0.02 (−0.08 to 0.04)	0.27	41
Alanine aminotransferase, U/L	−2.5 (−6 to 1)	0.24	42
Systolic blood pressure, mm Hg	0 (−4 to 5)	0.88	42
Diastolic blood pressure, mm Hg	1 (−9 to 10)	0.68	42
Psoriatic arthritis activity
DAPSA score	−3.52 (−8.62 to 2.77)	0.11	21
CRP, mg/L	−1.1 (−2 to −0.2)	0.002	31
Tender joint count	0 (−1 to 0)	0.29	68
Swollen joint count	0 (0–0)	0.03	66
Pain score	−1.0 (−1.75 to 0)	0.01	25
Patient global score	−0.5 (−1.67 to 0)	0.08	23
HAQ-DI	−0.05 (−0.25 to 0.08)	0.27	18
FACIT-Fatigue score	2.75 (−3 to 7.5)	0.14	18
EQ-5D index	0.01 (0–0.14)	0.14	18
Psoriasis body surface area, %	0.01 (0.0–1.0)	0.56	45

Note: Higher scores indicating worse disease activity.

^*Tender and swollen joint counts totaled 0 to 68. Pain score measured 0 to 10, with 10 denoting the worst pain imaginable. Patient global score measured 0 to 10, with 10 denoting the worst health status. HAQ-DI measured from 0 to 3, with 3 denoting worse health status. FACIT-Fatigue score measured 0 to 52, with 52 indicating no fatigue. EQ-5D index measured from 0 to 1, with 1 representing full health. CRP, C-reactive protein; DAPSA, Disease Activity in Psoriatic Arthritis; EQ-5D, EuroQol 5-domain; FACIT, Functional Assessment of Chronic Illness Therapy; HAQ-DI, Health Assessment Questionnaire–Disability Index; IQR, interquartile range.

We then performed a linear regression to estimate the effect of body weight reduction (percent from baseline) on disease outcomes. Each 1% reduction in body weight following GLP-1RA therapy demonstrated significant reductions in DAPSA score (β = −0.49; P = 0.04), tender joint count (β = −0.18; P = 0.01), EQ-5D score (β = 0.016, P < 0.001), total cholesterol level (β = −0.07 mmol/L; P = 0.003), low-density lipoprotein cholesterol level (β = −0.05 mmol/L; P = 0.04), and systolic blood pressure (β = −0.67 mm/Hg; P = 0.01) (Table 3).

Table 3.

Association between bodyweight reduction and change in outcomes following glucagon-like peptide-1 receptor agonist therapy^*

Outcome	Median change (IQR)a	P value	N
Cardiometabolic
Cholesterol, mmol/L	−0.07 (−0.11 to −0.03)	0.003	28
Triglyceride, mmol/L	−0.05 (−0.1 to 0)	0.07	28
Low-density lipoprotein, mmol/L	−0.05 (−0.1 to −0.003)	0.04	28
Systolic blood pressure, mm/Hg	−0.67 (−1.18 to −0.15)	0.01	42
Psoriatic arthritis activity
DAPSA score	−0.49 (−0.94 to −0.03)	0.04	21
Pain score	−0.09 (−0.20 to 0.02)	0.10	25
CRP, mg/L	−0.10 (−0.23 to 0.04)	0.15	31
Tender joint count	−0.18 (−0.32 to −0.05)	0.01	45
Swollen joint count	−0.02 (−0.06 to 0.02)	0.26	45
Psoriasis body surface area, %	0.01 (−0.02 to 0.04)	0.57	45
HAQ-DI	−0.02 (−0.04 to 0)	0.09	18
EQ-5D index	0.016 (0.008 to 0.023)	<0.001	18

Note: Higher scores indicating worse disease activity.

^*Pain score measured 0 to 10, with 10 denoting the worst pain imaginable. HAQ-DI measured from 0 to 3, with 3 denoting worse health status. EQ-5D index measured from 0 to 1, with 1 representing full health. CRP, C-reactive protein; DAPSA, Disease Activity in Psoriatic Arthritis; EQ-5D, EuroQol 5-domain; HAQ-DI, Health Assessment Questionnaire–Disability Index; IQR, interquartile range.

^aEstimates indicate the change in the corresponding outcome for each 1% reduction in bodyweight adjusted for baseline level of assessed activity.

We also examined the effect of the primary GLP-1RA indication (ie, diabetes or obesity) on outcomes. Patients prescribed a GLP-1RA for obesity (n = 36) lost a significantly higher percent of bodyweight (−7.3%, IQR −11.5 to −4.3 vs −0.2%, IQR −5.0 to 0.8; P = 0.002) compared to patients with diabetes (n = 12) (Supplementary Table 3). Although not statistically significant, an indication of obesity was also associated with higher improvement in the DAPSA score compared to that of diabetes (−7.1, IQR −11.6 to 4.2 vs 0.2 IQR −4.4 to 2.8; P = 0.102). Additionally, a subset of patients (n = 21) who reached a confirmed high dose of semaglutide (≥1.7 mg subcutaneous [SC]) or tirzepatide (≥10 mg SC) lost an average of 7.2% (IQR −11.2 to −4.9) of their initial body weight, with 76.2% of patients achieving a ≥5% loss of their initial body weight (Supplementary Table 4). Pain also decreased by one point (IQR −1.9 to 0; P = 0.026) as well as the DAPSA score (−7.4, IQR −10.3 to 0.03; P = 0.0116).

DISCUSSION

This real-world cohort study from two psoriasis-PsA centers demonstrates the high burden of cardiometabolic comorbidities among patients with PsA who were started on GLP-1RAs. GLP-1RA use resulted in substantial weight loss within one year of initiation, with 80% of patients losing weight and over 60% of patients achieving clinically significant weight loss (≥5% initial bodyweight). Additionally, weight loss was significantly greater in those prescribed GLP-1RAs for obesity rather than diabetes despite similar starting weights and BMIs. This is likely secondary to approved dosing, which is higher for weight loss than diabetes and is also reflected in our analysis of those taking confirmed high doses of GLP-1RAs, in which over 75% of patients had clinically relevant weight loss. The ability of GLP-1RAs to result in weight loss is of particular importance because PsA is likely driven in part by increased adiposity, leading to a proinflammatory milieu.²

Excess adiposity has been shown to act as both a risk factor of psoriasis and PsA and as an amplifier of symptoms. Patients with psoriasis and obesity are 1.2 to 2.7 times more likely to progress to PsA than those without obesity.² In those with existing PsA, obesity is linked to a 50% less chance of achieving sustained remission and worse pain, function, and quality of life.³ Individuals with obesity also demonstrate poor response to immunomodulator medications. Patients with PsA and concomitant obesity are up to 60% less likely to respond to tumor necrosis factor inhibitors—a mainstay in PsA treatment—in a dose-dependent method.¹¹ Weight loss of ≥5% has also been shown to reduce risk of diabetes and cardiovascular disease. Therefore, weight loss can help attenuate the risk of these comorbidities in PsA, a disease state in which patients are already at increased risk compared to the general population.

Our results show that in addition to weight loss, patients experienced improvement in markers of inflammation and pain, including those whose PsA medications were maintained at a stable dose during the follow-up time period. This suggests that the initiation of GLP-1RA alone may improve both subjective and objective measures of disease activity. However, it is unclear if these effects are caused by the weight loss associated with GLP-1RA use, direct actions of the therapy itself, or a combination of these mechanisms. Weight loss alone (eg, by diet and exercise) is effective in improving outcomes in PsA. In a study of 138 patients with PsA starting on tumor necrosis factor inhibitors and a diet intervention, patients with a ≥5% weight loss were four times more likely to achieve minimal disease activity (MDA) compared to those with <5% weight loss, with increasing amounts of weight loss conferring higher rates of MDA in a dose-dependent manner.¹² The DIPSA study randomly assigned patients with residual PsA symptoms to either the Mediterranean diet, a low-caloric diet, or general dietary recommendations and found that weight loss, regardless of diet type, was associated with improvement in PsA outcomes.¹³ Similarly, in the present study, we observed that PsA outcomes (DAPSA score, tender joint count, and quality of life) were associated with greater magnitude of weight loss, supporting the role of weight loss as an important adjunctive treatment for PsA.

In addition to weight loss, GLP-1RAs may have direct anti-inflammatory and immunomodulating properties, including modulating pathways specific to PsD. Proposed mechanisms include effects on invariant natural killer cells, γδ T cells, lymphocyte migration, and proinflammatory cytokines.^7–10 This is supported by clinical findings; improvement in psoriatic skin disease can be seen independent of or before weight loss in case reports and small cohort studies of patients initiating GLP-1RAs.¹⁴ Additionally, the only other study of GLP-1RA use in PsA observed 10 patients who were started on liraglutide and, at three months, observed an increase in MDA and improvements in skin psoriasis, quality of life, pain, and depressive symptoms without significant weight loss.¹⁵ Of note, however, no information was provided on PsA therapy use and changes in this study. Taken together, these findings support the hypothesis that GLP-1RAs may impact PsD beyond weight loss alone through direct anti-inflammatory effects.

Our study is limited by a small sample size and heterogenous population. Given the observational nature of our cohorts, some patients do have missing data. We reported the sample size for each outcome individually to ensure clarity in our results (see Tables 1 and 2). Importantly, GLP-1RAs were initiated and dose titrated for other indications (ie, obesity and diabetes) by predominantly outside providers and not with the specific intention to improve PsA activity. As such, some patients had minimal symptoms at baseline and lowered our ability to show change over time. In particular, our population had a baseline low burden of skin psoriasis, which did not allow us to assess any dermatologic effect. Additionally, although this study represents the longest to date in this population, the follow-up period is still relatively short, hampering our ability to observe long-term effects and assess persistence taking the drug. We were also unable to collect detailed information on side effects or adverse events in these patients (beyond discontinuation), which is an important factor in weighing the risks and benefits of any medication.

Although our results are preliminary, they support the notion that GLP-1RAs may potentially have a vital adjunctive role in the treatment of PsA. In patients who are overweight or have obesity, weight loss alone is a critical element in disease treatment, and GLP-1RAs have been highly effective in this regard. Additionally, GLP-1RAs may have direct effects on psoriatic skin and joint disease. Overall, these findings highlight the need for prospective, controlled studies to better quantify the clinical impact and possible optimal dosing of GLP-1RAs for patients with PsD. Further, studies looking at the biologic basis of GLP-1RA through biosampling and molecular endotyping are needed to tease out the underlying mechanisms of disease improvement.

Supplementary Material

Additional supplementary information cited in this article can be found online in the Supporting Information section (https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.70170).