scholarly journals Long-Acting Glucagon-Like Peptide-1 Receptor Agonist-Induced Rheumatoid Arthritis in a Patient with Type 2 Diabetes Mellitus

Author(s):  
Koji Kikkawa ◽  
Hiroto Hoshi ◽  
Atsushi Isoda ◽  
Kazuya Okada ◽  
Junichi Okada ◽  
...  

<b><i>Case Presentation:</i></b> We report a case of a male patient with rheumatoid arthritis (RA) diagnosed during treatment with a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist (once-weekly dulaglutide injection). At 3 months after dulaglutide initiation, he began experiencing left shoulder pain that continued despite treatment by an acupuncturist, indicating that the pain was not due to periarthritis scapulohumeralis. His HbA1c level was 7.3% at the 3-month follow-up. At the 6-month follow-up visit, the HbA1c level was 8.2%, the low-density lipoprotein cholesterol level was 132 mg/dL, and he expressed right shoulder pain. After 3 months, the HbA1c level was 9.0%, and his bilateral shoulder pain worsened, due to which he could not use his arms well. Routine laboratory testing revealed no other abnormalities at that time. However, several inflammatory and serological RA markers were detected, including an erythrocyte sedimentation rate of 73 (normal range, &#x3c;10) mm/h, a C-reactive protein level of 1.89 (normal range, 0.0–0.14) mg/dL, a rheumatoid factor level of 26 (normal range, 0–15) IU/mL, and an anti-cyclic citrullinated protein antibody level of 195 (normal range, &#x3c;4.5) U/mL. However, tests for antinuclear antibodies, anti-SS-A/Ro antibodies, and anti-RNP antibodies showed negative results. He was diagnosed with RA, and salazosulfapyridine (500 mg/day) was started. At 1 month after RA treatment initiation, his shoulder pain began showing improvement and improved HbA1c levels from 9.0% to 8.0%. <b><i>Discussion:</i></b> Thus, this case report suggests an association between RA and GLP-1. Based on a literature search in PubMed, we believe that this case report is the first to demonstrate that a patient with type 2 diabetes mellitus treated with a long-acting GLP-1 receptor agonist had RA. However, further research is needed to determine whether RA is one of the adverse effects of long-acting GLP-1 receptor agonists. <b><i>Conclusion:</i></b> During treatment with long-acting GLP-1 receptor agonists, it is necessary to consider the possibility of RA as a differential diagnosis when patients complain of persistent joint pain.

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Koji Yamamoto ◽  
Masatoshi Amako ◽  
Yoritsuna Yamamoto ◽  
Toyokazu Tsuchihara ◽  
Hitoshi Nukada ◽  
...  

Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system. In this study, we administered repeated intraperitoneal (i.p.) injections of exendin-4 to examine whether exendin-4 is able to facilitate the recovery after the crush nerve injury. Exendin-4 injection was started immediately after crush injury and was repeated every day for subsequent 14 days. Rats subjected to sciatic nerve crush exhibited marked functional loss, electrophysiological dysfunction, and atrophy of the tibialis anterior muscle (TA). All these changes, except for the atrophy of TA, were improved significantly by the administration of exendin-4. Functional, electrophysiological, and morphological parameters indicated significant enhancement of nerve regeneration 4 weeks after nerve crush. These results suggest that exendin-4 is feasible for clinical application to treat peripheral nerve injury.


RSC Advances ◽  
2017 ◽  
Vol 7 (85) ◽  
pp. 54178-54187 ◽  
Author(s):  
Lian Lu ◽  
Xiaoqing Su ◽  
Yantai Wang ◽  
Yi Luo ◽  
Jun Yang ◽  
...  

Exendin-4 (Ex-4), one of the important glucagon-like peptide-1 receptor (GLP-1R) agonists, has proven to be an effective antidiabetic agent for type 2 diabetes (T2D).


2020 ◽  
Vol 98 (3) ◽  
pp. 210-217
Author(s):  
A. Yu. Babenko ◽  
Yu. A. Kononova ◽  
M. V. Martjanova ◽  
A. V. Simanenkova ◽  
M. A. Kokina ◽  
...  

Due to the high efficiency of glucagon-like peptide-1 (GLP-1) receptor agonists therapy in only a part of patients, the search for predictors of response to the treatment is a relevant problem. Purpose. The purpose is to compare the efficacy of liraglutide and exenatide therapy in obese patients with type 2 diabetes mellitus (T2DM) and to evaluate the predictors of response to glycated hemoglobin (HbA1c), weight and lipids reduction. Material and methods. The study included 47 patients with type 2 diabetes and obesity who received GLP-1 receptor agonists therapy. 26 patients were treated with liraglutide, 21 patients were treated with exenatide. We measured the parameters of carbohydrate and lipid metabolism, the levels of hormones involved in glucose and lipids metabolism and in appetite regulation. Blood pressure was measured. These parameters were evaluated at baseline and after 24 weeks of treatment. Results. Patients receiving exenatide therapy showed a tendency towards more frequent HbA1c level reduction by 1% or more (60% versus 30.4%, p = 0.07). The effects of liraglutide and exenatide on weight and waist circumference were comparable. When assessing the predictors of response to the therapy, a more pronounced decrease in HbA1c level (by 1% or more) was in the patients with a higher initial HbA1c level (8.7 (8.2; 9.7) versus 8.2 (6.9; 8.7)%, p = 0.04), as well as with a higher initial GLP-1 level (0.12 (0.05; 0.17) versus 0.040 (0.01; 0.09) ng/ml.) A more significant decrease in the triglycerides (TG) level was detected in patients with a higher level of glucose-dependent insulinotropic peptide (GIP) before therapy (409 (316.0; 431.4) pg/ml in patients who reduced TG level by 30% or more and 331.5 (324.9; 367.1) pg/ml in patients with a lower decrease in TG level). Among the studied parameters, no predictors of body mass reduction were revealed. Conclusion. Measurement of HbA1c, GLP-1, GIP level may be useful to predict the efficacy of GLP-1 receptor agonists therapy.


2018 ◽  
Vol 315 (4) ◽  
pp. R595-R608 ◽  
Author(s):  
Jacob D. Brown ◽  
Danielle McAnally ◽  
Jennifer E. Ayala ◽  
Melissa A. Burmeister ◽  
Camilo Morfa ◽  
...  

Long-acting glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists (GLP-1RA), such as exendin-4 (Ex4), promote weight loss. On the basis of a newly discovered interaction between GLP-1 and oleoylethanolamide (OEA), we tested whether OEA enhances GLP-1RA-mediated anorectic signaling and weight loss. We analyzed the effect of GLP-1+OEA and Ex4+OEA on canonical GLP-1R signaling and other proteins/pathways that contribute to the hypophagic action of GLP-1RA (AMPK, Akt, mTOR, and glycolysis). We demonstrate that OEA enhances canonical GLP-1R signaling when combined with GLP-1 but not with Ex4. GLP-1 and Ex4 promote phosphorylation of mTOR pathway components, but OEA does not enhance this effect. OEA synergistically enhanced GLP-1- and Ex4-stimulated glycolysis but did not augment the hypophagic action of GLP-1 or Ex4 in lean or diet-induced obese (DIO) mice. However, the combination of Ex4+OEA promoted greater weight loss in DIO mice than Ex4 or OEA alone during a 7-day treatment. This was due in part to transient hypophagia and increased energy expenditure, phenotypes also observed in Ex4-treated DIO mice. Thus, OEA augments specific GLP-1RA-stimulated signaling but appears to work in parallel with Ex4 to promote weight loss in DIO mice. Elucidating cooperative mechanisms underlying Ex4+OEA-mediated weight loss could, therefore, be leveraged toward more effective obesity therapies.


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