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Weight-loss drugs and psoriasis

Weight Loss Drugs And Psoriasis
Reviewing the evidence

Individuals with psoriasis are more likely to be overweight; the heavier you are, the more severe your psoriasis is likely to be and the more at risk you are of developing type 2 diabetes.

Conversely, losing weight results in much less severe disease and fewer flares. The problem is that losing weight and maintaining a healthy weight, is very difficult. However, a new generation of medications called GLP-1 agonists, the best-known examples of which are semaglutide (Ozempic) and tirzepatide (Mounjaro), are now well established for their efficacy in promoting weight loss. In addition, there is preliminary evidence that these drugs also have a beneficial effect on psoriasis, especially in individuals who have type 2 diabetes.  At the same time, biologics – e.g. adalimumab and infliximab –  remain an important treatment option for patients with moderate-severe psoriasis. In future, the combination of GLP-1 agonists and biologics will likely usher in a new era in the treatment of psoriasis, especially for those patients who are also diabetic and obese.  All of this assumes that the problem of high-levels of discontinuation can be successfully addressed.

Patients with psoriasis and psoriatic arthritis, are more likely to be obese or overweight. Furthermore, there is a clear association between body weight – or body mass index (BMI) - and the severity of psoriasis: the heavier you are, the more severe your psoriasis is likely to be.1  There is also evidence to suggest that being overweight reduces the efficacy of many of the medications used to treat psoriasis.2  Put simply, if you are overweight you are more likely to have psoriasis and the medications used in your treatment, will be less effective.

Conversely, losing weight can help to improve the symptoms of psoriasis. This is unsurprising given that both psoriasis and inflammation are pro-inflammatory conditions and share the same basic inflammatory pathways, each exacerbating the other. Weight loss helps reduce overall inflammation, which can lead to fewer psoriasis flares and less severe skin disease.3

See the full article on obesity here:

GLP-1 Agonists – a new generation of weight-loss drugs

While weight loss through diet and exercise has been recommended as a way to manage psoriasis, as anyone who has attempted to lose weight will attest, it is exceedingly difficult. This why the new generation of weight-loss drugs, called GLP-1 agonists, has changed the dieting and weight-loss landscape almost overnight. These drugs work by mimicking the effects of a naturally occurring hormone called glucagon-like peptide-1 (GLP-1), which plays a role in regulating blood sugar and appetite. They help lower blood sugar levels, slow down digestion and reduce appetite, which can lead to weight loss. Whilst these drugs are commonly prescribed to people with diabetes to help manage their blood sugar, nowadays they are increasingly used to help people lose weight.

Perhaps the best known GLP-1 agonist is semaglutide which is available under two brand names, Ozempic and Wegovy. They are exactly the same drug, but Ozempic can only be prescribed for type 2 diabetes (mainly to protect supplies for diabetic patients), whilst Wegovy can be prescribed for weight loss. Both are given as injections, though there is now an oral (tablet) form of semaglutide available, called Rybelsus.

Tirzepatide (Mounjaro), on the other hand, is a dual-action medication, acting both as a GLP-1 agonist and a GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. It has been used in the treatment of type 2 diabetes since 2022, but was licensed for use as a weight loss drug in 2024. Moreover, evidence suggests that this dual action might account for the fact that Mounjaro appears to be somewhat more effective than Wegovy.

In a recently published study, sponsored by Eli Lilly (the company which developed Mounjaro), involving 751 obese subjects, without diabetes:

  • 32% of people lost a quarter of their body weight on Mounjaro, compared to 16% on Wegovy
  • Those on Mounjaro lost an average of 18 cm from their waistline compared with 13 cm on Wegovy
  • Those subjects taking Mounjaro had better blood pressure, blood sugar and cholesterol levels.
  • Side-effects were the same in both groups.4

Several other studies have shown a similar advantage for Mounjaro. In a systematic review combining data from four trials, a total of 28,827 patients (14,870 tirzepatide/13,928 semaglutide) with type 2 diabetes, were followed for just under one-year. At the end of that period, average weight reduction across four studies for tirzepatide was 11.4% and for semaglutide 7.3%.5 Another study involving 18,386 overweight or obese subjects, again showed tirzepatide to be associated with significantly greater weight loss than semaglutide.6

In the UK, patients typically qualify for GLP-1 agonists if they have a BMI ≥30 kg/m2 (classed as obesity) or a BMI ≥27 kg/m2 (classed as overweight) if you also have weight-related issue such as high cholesterol, pre-diabetes, increased BP etc. In practice, however, this guideline is widely ignored and these drugs are widely available on the internet without any requirement for an in-person medical check with a GP. 

Does treating obesity with GLP-1 agonists improve psoriasis?

Given the link between psoriasis and obesity, treating obesity with GLP-1 agonists may offer a promising approach to improving psoriasis outcomes in those affected by both conditions. In fact, a number of studies have demonstrated the efficacy of GLP-1 agonists in treating psoriasis in patients with type 2 diabetes.7-10 All subjects in these studies showed significant improvements in their psoriasis, as measured by standard questionnaires, such as the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI). The problem is that these were very small trials, sometimes containing only one or two patients and 25 patients at the most. This makes it impossible to draw any firm conclusions. Moreover, when it comes to disease impact in patients without type 2 diabetes, the evidence is inconclusive. In a study involving 20 non-diabetic obese patients, participants were given either liraglutide - a GLP-1 agonist - or placebo for 8-weeks.11 No significant improvements were observed either in the PASI score or in the DLQI in the study and there was no improvement in the level of inflammatory markers in the liraglutide group. These findings suggest that the metabolic status of the patient may influence the impact on psoriasis and that the effects of GLP-1 agonists may be more pronounced in patients with concurrent metabolic dysfunction.

What all this this amounts to, is that although initial studies suggest that GLP-1 agonists may offer benefits for patients with psoriasis and type 2 diabetes, they are not believed to be as effective as the current group of biologic therapies, e.g. adalimumab, infliximab (see below) which remain the first choice in treating moderate-severe psoriasis. Note however, that no studies to date have included patients with psoriatic arthritis and there is currently no evidence to suggest that GLP-1 agonists will be effective in treating normal-weight, non-diabetic patients with psoriasis. Clearly large-scale trials are needed to assess the efficacy of GLP-1 agonists in broader patient populations, including patients with psoriasis, psoriatic arthritis and other chronic inflammatory conditions. Several such studies are currently underway.

What about GLP-1 agonists with biologics?

Biologics for psoriasis are medications designed to target specific parts of the immune system and inflammatory pathways that are overactive in people with psoriasis. For patients with moderate-severe psoriasis, they provide a more precise and effective treatment when compared to older therapies. There are many different types of biologic drugs, depending on the mechanism of action; examples include adalimumab, infliximab, and etanercept.

There is little information on the interactions between GLP-1 agonists and biologics, though at present, it does not appear that GLP-1 agonists have any direct negative effects on biologics. Nevertheless, we must bear in mind that biologics work by dampening certain immune responses, which can make people more vulnerable to infections. Since GLP-1 drugs also have an effect on inflammation and the immune system, theoretically combining them with biologics could create a heightened risk of infection or immune-related issues. 

On the other hand, GLP-1 agonists not only reduce inflammation, but also improve metabolic parameters associated with obesity, e.g. blood sugar levels, cholesterol and high blood pressure. So far from being antagonistic, biologics and GLP-1 agonists may actually have a powerful synergistic effect in which the biologic addresses the skin and joint manifestations of the disease, whilst the GLP-1 agonist reduces inflammation, improves the subject’s metabolic profile and reduces body weight, thus making the individual more receptive to biologic treatment. It is an approach which has huge promise.

To explore the potential of this combined approach, the pharma company Eli Lilly, is currently sponsoring 2 studies in overweight patients with psoriasis. In the first, researchers are using a combination of tirzepatide (a dual GLP-1/GIP agonist), together with the biologic, ixekizumab (an IL-17A inhibitor). In the second study, the combination of tirzepatide and ixekizumab is being compared with ixekizumab alone. Note, however, that neither of these trials includes normal weight, non-diabetic patients with psoriasis and/or psoriatic arthritis.

Taken together, the results of these trials should begin to reveal the impact of the combination of a biologic with a GLP-1 agonist in the treatment of psoriasis. It could well prove to be a game-changer, especially given that many patients with psoriasis are overweight or obese and a significant minority - around 11% - also have type 2 diabetes.12

As research continues, there is little doubt that GLP-1 receptor agonists will soon be an essential part of managing chronic inflammatory skin diseases by addressing the metabolic factors that impact treatment outcomes and quality of life.

The obstacle in the way

A potential problem which may prevent the full potential of GLP-1 agonists being realised, is the high discontinuation rates now being reported. A recent study involving 125,474 adults with overweight or obesity, found that 46.5% of patients with Type 2 diabetes and 64.8% of non-diabetics discontinued GLP-1 medications within one year of starting treatment.13  Another large study involving 195,915 adults who began GLP-1 agonist treatment in 2021, found that at 12-months, 50.3% of obese patients and 35.8% of Type 2 diabetics, had discontinued their medication, as had 34% of those with both conditions.14  Older patients and those from poorer socio-economic groups were more likely to discontinue, as were those experiencing significant side-effects – including gastrointestinal upset such as nausea, diarrhoea and vomiting. 

The concern here, of course, is that when patients discontinue these drugs, they regain the weight they lost. A recent of review of 11 studies of older and newer GLP-1 weight loss drugs by the University of Oxford, found that patients typically lost 8kg on weight loss jabs but returned to their original weight within 10 months of stopping them.

These trends have serious implications for patients with psoriasis as well as for those with Type 2 diabetes and obesity. If patients discontinue GKP-1 agonists and regain the weight they lost, what implications does this have for their psoriasis?  Does it result in an exacerbation of their disease?  And for those patients with type 2 diabetes, what would such weight regain do to their diabetic control?  More broadly, is it worth the expense of providing these drugs on the NHS, if the benefit is relatively short-lasting? It seems clear that if treatment is to be life-long, we will need to think very hard about how we can mitigate these high rates of discontinuation and their long-term health implications.

Key Conclusions

  • Both obesity and psoriasis are inflammatory conditions with the same inflammatory pathways involved.
  • In individuals with psoriasis, increasing body weight is associated with a worsening of their symptoms, whilst reducing weight results in an improvement.
  • GLP-1 receptor agonists, including semaglutide and tirzepatide, are well-recognised for their efficacy in promoting weight loss, with tirzepatide being consistently more effective than semaglutide.
  • Studies on the impact of GLP-1 agonists in psoriatic patients with type 2 diabetes and/or obesity, suggest benefit, but these trials are very small and – as yet – do not allow of any firm conclusions.
  • The combination of biologic drugs and GLP-1 agonists, offers a new therapeutic dimension for the treatment of psoriasis, in which both overweight and the associated dysmetabolism are addressed at the same time as the skin and/or joint manifestations of psoriasis.
  • Currently, no trials have examined the impact of GLP-1 agonists on normal weight, non-diabetic subjects and no trial either of GLP-1 agonists alone or in combination with biologics, has included patients with psoriatic arthritis.
  • A major concern which will need to addressed, is the high rates of discontinuation – up to 50% - observed in recent studies.
  • Assuming the results of the ongoing trials are positive, GLP-1 agonists will quickly become an essential addition to the growing armamentarium of therapeutics for patients with psoriasis, especially for those who are obese and have type 2 diabetes.

Author:
Dr David Ashton MD PhD
June 2025

References

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