sitagliptin-phosphate and Arthritis

Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel therapy widespread used in type 2 diabetes mellitus. We describe 3 cases of polyarthritis which delay of appearance strongly suggests a link with DPP4 inhibitors. Three patients presented with bilateral, symmetrical, seronegative polyarthritis after introduction of DPP4 inhibitors (sitagliptine (n = 2) and vildagliptine (n = 1)). Two patients also developed xerostomia and xerostomia, and laboratory test results showed normal values of CRP and erythrocyte sedimentation rate. Joints X-rays were normal. One patient was diagnosed with primary Sjögren's syndrome and treated with hydroxychloroquine, methotrexate and prednisone, with a poor efficacy. When sitagliptine was stopped, all symptoms disappeared, leading to methotrexate and prednisone discontinuation within a month. There were no immunological abnormalities in the 2 other patients, but a chronic viral hepatitis B was found in one patient. Eventually, discontinuation of DPP4 inhibitors led to resolution of symptoms in 1 and 3 weeks for both patients. DPP4 inhibitors seemed to trigger bilateral, non-erosive, seronegative polyarthritis in our 3 patients. DPP4, also known as CD26, is expressed on many cells including lymphocytes and fibroblasts, and its inhibition may lead to immunomodulating effect as suggested by clinical and in vitro studies.

Topics: Adamantane; Arthritis; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Nitriles; Pyrazines; Pyrrolidines; Risk Factors; Sitagliptin Phosphate; Triazoles; Vildagliptin

To validate the potential anti-inflammatory and analgesic role of sita- and vildagliptin, five different experimental models were used in mice: i) mustard oil-induced ear edema, ii) neutrophil accumulation, iii) mechanical and iv) thermal touch sensitivity in complete Freund's adjuvant-induced arthritis and v) capsaicin-induced plasma extravasation in the urinary bladder. For the complete examination period in i) the dose of 10mg sitagliptin as well as 1-10mg vildagliptin was found to significantly decrease ear edema as compared to positive control (p<0.05, n=8/group). All doses of sitagliptin provided an anti-inflammatory effect p<0.005 (n=10/group) in test ii) and an analgesic effect in iii) except 3mg. Vildagliptin was similarly effective in test ii) (p<0.005, n=10/group) as sitagliptin, but it failed to affect mechanical touch sensitivity. Unlike mechanical touch sensitivity, both gliptins could beneficially act on the thermal threshold (p<0.05, n=10/group). And only in tests v) could both gliptins reverse inflammation. Further studies are needed to support the suggestion that the utilization of these beneficial effects of gliptins may be considered in the treatment of Type 2 diabetic patients.

Topics: Adamantane; Allyl Compounds; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Capsaicin; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Freund's Adjuvant; Isothiocyanates; Male; Mice; Nitriles; Pyrrolidines; Sitagliptin Phosphate; Temperature; Urinary Bladder; Vildagliptin

Dipeptidyl peptidase-4 inhibitors (DPP-4Is) inhibit the inactivation of incretin hormones while also affecting the immune system, since CD26/DPP-4 is involved in immune regulation. The current study shows that the use of DPP-4Is as therapy for type 2 diabetes patients may induce joint symptoms with decrease in plasma SDF-1α level.

Topics: Adult; Aged; Aged, 80 and over; Arthritis; Chemokine CXCL12; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Triazoles