Background/Purpose: Glucagon-like peptide-1 (GLP-1) analogues such as liraglutide, which are used for the treatment of type 2 diabetes (T2DM), mimic the action of endogenous incretin hormones through both enhancing post-prandial pancreatic glucose-dependent insulin release and promoting early satiety. Recent evidence indicates novel anti-inflammatory effects of GLP-1 analogues, including the amelioration of TNF inflammatory responses on human endothelial cells, and reduction in monocyte TLR2, TLR4 and TNF expression following treatment with GLP-1 analogues for T2DM. We have previously shown decreased inflammatory activity of invariant Natural Killer T (iNKT), modulation of monocyte cytokine secretion and amelioration of skin psoriasis in a cohort of patients with concomitant psoriasis and T2DM. Here we investigate a role for liraglutide in the amelioration of inflammatory arthritis disease activity in a cohort of patients undergoing liraglutide treatment for concomitant T2DM. 

Methods: Following institutional ethics committee approval, patients with T2DM and a concomitant diagnosis of either rheumatoid arthritis (n=11) or psoriatic arthritis (n=4 ) were recruited from rheumatology out patient clinics and commenced on the GLP-1 analogue, liraglutide 1.2mg s/c od. No changes were made to patient Disease Modifying Anti Rheumatic or biological drug therapies for the duration of the study. DAS28 scores, weight, HbA1C, were recorded at baseline and weeks 6, 12 and 24. DAS28 outcomes were  defined by EULAR good, or moderate vs non-responders. Results expressed as Mean + SE.

Results:  Patients had active arthritis (DAS28 4.38 + 0.4) and inadequate glycaemic control Hba1C (55 + 5.1) at baseline. Following liraglutide therapy 9 patients achieved DAS28 response (DAS28 = 4.2 + 0.8 pre, 2.7 + 0.5 post) vs 6 non-responders (DAS28 = 4.7 + 0.8 pre, 5.0 + 2.7 post ). Significant weight loss was seen in DAS28 responders (94 + 5 pre, 90.6 + 5.2kg, p=0.008) but not non-responders (93.8 + 3.3kg pre, 95 + 2.8kg post, p = 0.79). A significant fall in HbA1C was seen in DAS28 responders (60.5 + 6.3 pre vs 45.5 + 2.1 post, p = 0.012) but not non-responders (47.1+9.5 pre vs 39.4+13, p=0.144). A significant fall in SJC28 was seen in DAS28 responders (3.3 + 0.9 pre vs 1.2 + 0.6, p = 0.027) but not non-responders (4.2 + 2.8 pre vs 4.8 + 3.2, p = 0.66). Weight loss  following liraglutide was also significantly associated with achieving a DAS28 response by Chi Square analysis (p = 0.044). No significant differences were observed in baseline levels of DAS28, weight, HbA1C, SJC, ESR or CRP analysed according to subsequent DAS28 response grouping. 

Conclusion: In a cohort of patients with both inflammatory arthritis and T2DM, clinical efficacy of  the GLP-1 analogue liraglutide in reducing HbA1C and inducing weight loss was significantly associated with a concomitant reduction in inflammatory arthritis clinical disease activity by EULAR DAS28 response criteria. Further studies investigating common pathways of inflammation between these diseases may lead to novel therapeutic stretegies in the treatment of inflammatory arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-with-the-glucagon-like-peptide-1-analogue-liraglutide-is-associated-with-amelioration-of-disease-activity-in-a-prospective-cohort-study-of-patients-with-inflammatory-arthritis/