Are there any findings on tirzepatide (dual GLP‑1/GIP receptor agonist) regarding its effect on psoriasis?

Tirzepatide and Psoriasis: Emerging Evidence

GLP-1 receptor agonists, including tirzepatide, show promising effects in reducing psoriasis severity, particularly in patients with metabolic comorbidities, though the evidence for tirzepatide specifically remains limited compared to other agents in this class.

Current Evidence for GLP-1 Receptor Agonists in Psoriasis

Liraglutide: The Most Studied Agent

• Liraglutide 1.2 mg daily significantly reduced psoriasis severity in a prospective cohort of 7 patients with psoriasis, obesity, and type 2 diabetes, decreasing median PASI from 4.8 to 3.0 (P = 0.03) after 10 weeks of treatment 1
• Quality of life improved substantially, with median DLQI decreasing from 6.0 to 2.0 (P = 0.03) in the same cohort 1
• The mechanism appears to involve increased circulating invariant natural killer T (iNKT) cells, which rose from 0.13% to 0.40% of T lymphocytes (P = 0.03), alongside a 54% decrease in TNF-alpha-producing monocytes 1

Semaglutide: Broader Population Benefits

• Semaglutide treatment in patients with psoriasis was associated with dramatically reduced all-cause mortality (HR 0.219,95% CI 0.123-0.391; P < 0.001) compared to other antidiabetic/antiobesity drugs in a large cohort of 3,048 matched patients 2
• Major adverse cardiac events were reduced by 44% (HR 0.561,95% CI 0.442-0.714; P < 0.001) in psoriasis patients treated with GLP-1RAs 2
• Psychiatric comorbidities improved, with lower risks for alcohol abuse (HR 0.346,95% CI 0.174-0.685; P = 0.009) and substance abuse (HR 0.510,95% CI 0.350-0.743; P = 0.002) 2
• Risk reductions were more pronounced in patients with psoriasis than in those with obesity or diabetes without psoriasis, suggesting disease-specific benefits 2

Tirzepatide-Specific Considerations

Theoretical Advantages Over Single GLP-1 Agonists

• Tirzepatide's dual GIP/GLP-1 receptor activation provides enhanced metabolic benefits, including delayed gastric emptying, suppressed appetite, and improved insulin secretion compared to semaglutide's single-receptor action 3
• Superior weight loss with tirzepatide (20.9% at 72 weeks with 15mg dose) compared to semaglutide (14.9%) may provide additional benefit for psoriasis patients, as obesity is a known exacerbating factor 3
• Broader cardiometabolic improvements with tirzepatide, including superior triglyceride reduction and blood pressure control, may address the systemic inflammation underlying psoriasis 3

Proposed Mechanisms in Psoriasis

• GLP-1RAs mitigate psoriasis through both systemic and local effects: weight loss, improved glycemic control, regulation of iNKT cells, and AMPK activation in psoriatic plaques 4
• Anti-inflammatory and immunomodulatory properties of GLP-1 receptor activation may directly impact the immune dysregulation driving psoriasis 4
• Benefits appear particularly notable in patients with coexisting metabolic conditions (obesity, type 2 diabetes), which are highly prevalent in psoriasis populations 4

Clinical Decision Algorithm

When to Consider GLP-1RAs (Including Tirzepatide) for Psoriasis Patients

Primary indications:

• Psoriasis patients with BMI ≥30 kg/m² or BMI ≥27 kg/m² with metabolic comorbidities (type 2 diabetes, hypertension, dyslipidemia) 3
• Psoriasis patients with established cardiovascular disease, where semaglutide 2.4mg offers proven cardiovascular benefit (20% reduction in CV death, MI, or stroke) 3
• Psoriasis patients with type 2 diabetes requiring superior glycemic control, where tirzepatide achieves HbA1c reductions of 1.87-2.59% 3

Medication selection:

• Choose semaglutide 2.4mg weekly for patients with established cardiovascular disease due to proven cardiovascular outcomes (HR 0.74,95% CI 0.58-0.95) 3
• Choose tirzepatide 15mg weekly for patients requiring maximum weight loss (20.9% vs 14.9% with semaglutide), as obesity exacerbates psoriasis 3
• Choose liraglutide 1.2-3.0mg daily if weekly injections are not tolerated, though efficacy is lower (5.2-6.1% weight loss) 3

Monitoring Requirements

• Assess psoriasis severity (PASI) and quality of life (DLQI) at baseline and every 3 months to evaluate treatment response 1
• Monitor weight, blood pressure, and cardiovascular risk factors every 3 months after reaching maintenance dose 3
• Evaluate for gastrointestinal adverse effects (nausea 17-22%, diarrhea 13-16%, vomiting 6-10%) during dose titration 5
• Screen for contraindications: personal or family history of medullary thyroid cancer or MEN2 syndrome 3, 5

Critical Limitations and Caveats

Evidence Gaps

• No published clinical trials specifically evaluate tirzepatide in psoriasis patients, limiting definitive recommendations 4
• Existing evidence is limited by small cohort sizes (e.g., 7 patients in the liraglutide study), heterogeneous patient populations, and confounding effects of concurrent therapies 4, 1
• Larger, long-term randomized controlled trials are needed to validate efficacy, optimize dosing, and determine the role of GLP-1RAs as standalone or adjunctive therapies 4

Practical Considerations

• Benefits may be primarily mediated through weight loss and metabolic improvement rather than direct anti-psoriatic effects, making efficacy uncertain in lean psoriasis patients without metabolic comorbidities 4
• Cost is substantial (~$1,272-$1,619 per 30-day supply), requiring long-term financial planning and insurance authorization 3
• Lifelong treatment is typically necessary to maintain benefits, as discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 3

Safety Monitoring

• Discontinue tirzepatide at least 3 weeks before elective surgery due to delayed gastric emptying and aspiration risk, even with extended fasting 5
• Monitor for pancreatitis and gallbladder disease, though causality has not been definitively established 5
• Use with caution in patients with history of pancreatitis or severe gastroparesis 5

Practical Implementation

For psoriasis patients with obesity and/or type 2 diabetes:

• Initiate tirzepatide 5mg weekly if maximum weight loss is the priority, titrating every 4 weeks to 10mg, then 15mg based on tolerance 3
• Initiate semaglutide 0.25mg weekly if cardiovascular disease is present, titrating to 2.4mg weekly over 16 weeks 3
• Combine with lifestyle modifications: 500-kcal reduction below daily requirements, minimum 150 minutes/week physical activity, and resistance training 3
• Reduce or discontinue sulfonylureas when initiating GLP-1RAs to prevent hypoglycemia 3
• Reduce basal insulin by 20% when starting GLP-1RA therapy in diabetic patients 3

Expected outcomes:

• Psoriasis improvement may be observed within 10 weeks, though optimal response may require 3-6 months 1
• Weight loss of 15-21% is achievable with tirzepatide 15mg at 72 weeks, potentially improving psoriasis severity through metabolic pathways 3
• Cardiovascular risk reduction occurs independently of psoriasis improvement, providing additional benefit 2