glucagon-like-peptide-1 and Psoriasis

Psoriasis is a chronic recurrent inflammatory skin disease with a high risk of diabetes based on disease severity.. The aim of the study was to evaluate the efficacy of different hypoglycemic medications in patients with psoriasis.. A systematic review and meta-analysis of studies were conducted to evaluate the efficacy of hypoglycemic medications in patients with psoriasis. The primary outcome was of changes in the psoriasis area and severity index (PASI) score, and a 75% improvement in PASI from baseline (PASI75). Subgroup analysis was used to investigate associations among the types of hypoglycemic medicines, combination therapy, patient characteristics, course of treatment, and curative effect.. We included 3,286 patients from 19 studies to explore the effects of hypoglycemic medications. Patients randomized to receive hypoglycemic medicines showed a more significant decrease in the PASI score (standard mean difference = -0.55, 95% confidence interval (CI): -0.87 to -0.23, p = 0.0007) and a higher PASI75 ratio (RR: 1.80, 95% CI: 1.20-2.71, p = 0.0046). Patients consuming thiazolidinediones (TZDs) were more likely to reach PASI75 than those consuming glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 inhibitors. The combined use of hypoglycemic medicines had an add-on effect on the standard psoriasis treatment, and the proportion of PASI75 in the combination group was nearly four times that in the noncombination group (p = 0.0216). In addition, hypoglycemic medications can reduce body weight, waist circumference, triglyceride, total cholesterol, low-density lipoprotein, and systolic blood pressure.. Certain hypoglycemic drugs, such as GLP-1 RAs and TZDs, are beneficial for treating psoriasis. Multidisciplinary collaboration is recommended for the management of systemic inflammation in patients with psoriasis and diabetes.

Topics: Chronic Disease; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Psoriasis; Randomized Controlled Trials as Topic; Thiazolidinediones

GLP-1 receptor agonists (GLP-1 RAs) with exenatide b.i.d. first approved to treat type 2 diabetes in 2005 have been further developed to yield effective compounds/preparations that have overcome the original problem of rapid elimination (short half-life), initially necessitating short intervals between injections (twice daily for exenatide b.i.d.).. To summarize current knowledge about GLP-1 receptor agonist.

Topics: Animals; Blood Glucose; Body Weight; Cardiovascular System; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Hypoglycemia; Immunoglobulin Fc Fragments; Insulin; Liraglutide; Neurodegenerative Diseases; Peptides; Psoriasis; Recombinant Fusion Proteins

Psoriasis is a chronic inflammatory skin disease with a global prevalence of 2-3%. In recent years it has been established that patients with psoriasis carry an increased risk of type 2 diabetes, but the underlying pathophysiological mechanisms remain unclear. The association is most likely due to a combination of shared genes, immunoinflammatory mechanisms and a number of diabetes risk factors in patients with psoriasis. The current review summarises the evidence in the field and calls for attention on diabetes risk assessment, preventive measures and treatment in patients with psoriasis.

Topics: Alcohol Drinking; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucocorticoids; Humans; Incretins; Metabolic Syndrome; Obesity; Psoriasis; Risk Factors; Smoking

It has been reported that GLP-1 analogue can improve the skin lesions of psoriasis. However further research is needed to confirm that finding.. The study can provide further data regarding the efficacy and safety of GLP-1 analogue liraglutide in the treatment of psoriasis patients with type 2 diabetes.. We recruit 7 psoriasis patients with type 2 diabetes, and use hypodermic injection with liraglutide1.8 mg. In 12 weeks of treatment, we estimate the difference of before and after respectively, likeBMI, waist circumference, fasting blood glucose, fasting C-peptide, HbA1c, blood lipid levels, CRP, PASI, DLQI, skin tissue and pathological analysis of psoriasis.. GLP-1 analogueliraglutide can improve the skin lesions of psoriasis patients with type 2 diabetes effectively, especially for extremely severe psoriasis patients. Its therapeutic effect may be related to anti-inflammatory, hypoglycemic and reducing weight.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Liraglutide; Male; Middle Aged; Prognosis; Prospective Studies; Psoriasis

A few case reports suggest that incretin-based therapies could improve psoriasis in patients with type 2 diabetes, the mechanism(s) of which remain unclear.. To determine the effects after 16-20 weeks of treatment with a glucagon-like peptide (GLP)-1 analogue on clinical severity and histopathological aspects of psoriasis in patients with type 2 diabetes, and to examine the presence of γδ T cells and the expression of interleukin (IL)-17 in psoriasis before and after treatment.. Seven patients with type 2 diabetes and psoriasis were followed. Psoriasis Area and Severity Index (PASI) was measured at baseline (T0) and after 7 ± 1 (T1) and 18 ± 2 (T2) weeks' treatment with exenatide/liraglutide. The histopathological pattern of psoriasis, and flow cytometry and immunological data (γδ T-cell percentage and IL-17 expression) were obtained from psoriatic and control sites.. The mean PASI decreased from 12·0 ± 5·9 to 9·2 ± 6·4 (P = 0·04). Histological analysis showed a reduction in epidermal thickness after treatment. The dermal γδ T-cell percentage was higher in psoriatic lesions than in control specimens (P = 0·03), as was IL-17 expression (P = 0·018). A reduction of γδ T cells from 6·7 ± 4·5% to 2·7 ± 3·8% (P = 0·05) was demonstrated in the six patients with improved/unchanged PASI. A correlation between PASI and γδ T-cell percentage evolution during therapy (T2-T0) was noted (r = 0·894, P = 0·007). IL-17 was reduced in the four patients with the highest PASI reductions.. The administration of a GLP-1 analogue improved clinical psoriasis severity in patients with type 2 diabetes. This favourable outcome was associated with a decrease of dermal γδ T-cell number and IL-17 expression. Further studies are needed to establish long-term efficacy in (diabetic) patients with psoriasis.

Topics: Adult; Chronic Disease; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incretins; Interleukin-17; Liraglutide; Lymphocyte Count; Male; Middle Aged; Peptides; Prospective Studies; Psoriasis; Severity of Illness Index; Skin; T-Lymphocytes; Treatment Outcome; Venoms

A 59-year old man with moderate and stable psoriasis through 15 years was admitted to our Department with inadequately controlled type 2 diabetes. Treatment was initiated with the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide. The patient experienced marked improvement in his psoriasis immediately after the start of liraglutide treatment. Itching stopped within days, scaling was reduced and spots of normal skin emerged. After 3 months, psoriasis was still improving. Excellent glycaemic control and a weight loss of approximately 8 kg over 3 months were moreover obtained. The patient had previously been well controlled in his diabetes without improvement in psoriasis, and the effect of liraglutide on psoriasis started before weight loss occurred. We discuss the possibility of a direct anti-inflammatory effect of liraglutide in psoriasis as well as indirect effects through improvement in comorbidities such as overweight. Randomized clinical trials are needed to reveal whether GLP-1R agonists represent a new therapeutic option for psoriasis.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Liraglutide; Male; Middle Aged; Psoriasis; Receptors, Glucagon; Treatment Outcome

Topics: Acitretin; Chronic Disease; Drug Therapy, Combination; Glucagon-Like Peptide 1; Humans; Incretins; Keratolytic Agents; Liraglutide; Male; Middle Aged; Psoriasis

Diabetes and obesity are more prevalent amongst psoriasis patients as is disturbance of the innate immune system. GLP-1 analogue therapy considerably improves weight and glycaemic control in people with type 2 diabetes and its receptor is present on innate immune cells.. We aimed to determine the effect of liraglutide, a GLP-1 analogue, on psoriasis severity.. Before and after 10 weeks of liraglutide therapy (1.2 mg subcutaneously daily) we determined the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) in seven people with both psoriasis and diabetes (median age 48 years, median body mass index 48.2 kg/m(2) ). We also evaluated the immunomodulatory properties of liraglutide by measuring circulating lymphocyte subset numbers and monocyte cytokine production.. Liraglutide therapy decreased the median PASI from 4.8 to 3.0 (P = 0.03) and the median DLQI from 6.0 to 2.0 (P = 0.03). Weight and glycaemic control improved significantly. Circulating invariant natural killer T (iNKT) cells increased from 0.13% of T lymphocytes to 0.40% (P = 0.03). Liraglutide therapy also effected a non-significant 54% decrease in the proportion of circulating monocytes that produced tumour necrosis factor alpha (P = 0.07).. GLP-1 analogue therapy improves psoriasis severity, increases circulating iNKT cell number and modulates monocyte cytokine secretion. These effects may result from improvements in weight and glycaemic control as well as from direct immune effects of GLP-1 receptor activation. Prospective controlled trials of GLP-1 therapies are warranted, across all weight groups, in psoriasis patients with and without type 2 diabetes.

Topics: Adult; Aged; Animals; Cats; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Humans; Liraglutide; Male; Obesity; Prospective Studies; Psoriasis

The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.. We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells.. The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro.. The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.

Topics: Cell Count; Cell Line; Cytokines; Diabetes Mellitus, Type 2; Female; Gene Expression Regulation; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Immunologic Factors; Liraglutide; Male; Middle Aged; Molecular Targeted Therapy; Natural Killer T-Cells; Obesity; Psoriasis; Receptors, Glucagon; RNA, Messenger; Severity of Illness Index; Signal Transduction; Skin

Type 2 diabetes mellitus is characterised by beta cell failure, which frequently develops in the setting of insulin resistance. Inflammation contributes to the pathophysiology of type 2 diabetes by impairing insulin action in peripheral tissues and via reduction of beta cell function. Inflammation may also play an important role in the development of complications that arise in patients with type 2 diabetes. Hence, the anti-inflammatory actions of commonly used glucose-lowering drugs may contribute, indirectly, to their mechanisms of action and therapeutic benefit. Herein we highlight the anti-inflammatory actions of glucagon-like peptide-1 (GLP-1), which exerts direct and indirect actions on immune function. The observations that GLP-1 receptor agonists exert anti-inflammatory actions in preclinical studies, taken together with case reports linking improvements in psoriasis with GLP-1 receptor agonist therapy, illustrates the emerging clinical implications of non-classical anti-inflammatory actions of incretin-based therapeutics.

Topics: Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Male; Natural Killer T-Cells; Psoriasis; Receptors, Glucagon

Psoriasis is a common inflammatory skin disease and obesity constitutes a risk factor for the disease. Obese patients with psoriasis are often more difficult to treat and are at increased risk for dyslipidemia, diabetes, hypertension and cardiovascular disease. Case reports suggest that gastric bypass surgery in patients with psoriasis may result in complete remission of the disease. A substantial weight loss is achieved in the months following surgery, which is likely to reduce psoriasis symptoms and risk of comorbidities. Interestingly, however, it has been described that improvement of psoriasis is initiated immediately following surgery before any weight loss could have happened. We hypothesize that the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1) is responsible for this effect. The levels of GLP-1 have been shown to increase up to 20 times after gastric bypass surgery. This most likely contributes importantly to the acute remission of type 2 diabetes, which is often induced by gastric bypass operations. The hormone is not hypersecreted after the purely restrictive bariatric procedure gastric banding and no case reports exist on improvement in psoriasis following gastric banding. Intriguingly, recent studies describe that GLP-1 may convey anti-inflammatory effects in addition to its effects on glucose homeostasis. Also, GLP-1 reduces appetite and gastrointestinal motility including gastric emptying, which reduces food intake and leads to weight loss. Thus, both a direct anti-inflammatory effect of GLP-1 as well as an indirect effect through weight loss could contribute to improvement in psoriasis. A potential involvement of GLP-1 in the remission of psoriasis observed after bariatric surgery offers exciting possibilities for research and eventually perhaps new ways of anti-psoriatic treatment.

Topics: Gastric Bypass; Glucagon-Like Peptide 1; Humans; Models, Biological; Obesity; Psoriasis; Remission Induction; Skin; Weight Loss