A systematic review on the correlation between selective dipeptidyl peptidase inhibitor vildagliptin and risk of arthralgia/osteoarthritis

TAO Yilin; HUANG Youming; LIN Huie

doi:10.3969/j.issn.1006-0111.2016.06.015

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2016 > 34(6): 540-545

TAO Yilin, HUANG Youming, LIN Huie. A systematic review on the correlation between selective dipeptidyl peptidase inhibitor vildagliptin and risk of arthralgia/osteoarthritis[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 540-545. doi: 10.3969/j.issn.1006-0111.2016.06.015

Citation:

TAO Yilin, HUANG Youming, LIN Huie. A systematic review on the correlation between selective dipeptidyl peptidase inhibitor vildagliptin and risk of arthralgia/osteoarthritis[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 540-545. doi: 10.3969/j.issn.1006-0111.2016.06.015

A systematic review on the correlation between selective dipeptidyl peptidase inhibitor vildagliptin and risk of arthralgia/osteoarthritis

doi: 10.3969/j.issn.1006-0111.2016.06.015

Department of Pharmacy, No. 180 Hospital of PLA, Quanzhou 362000, China

Received Date: 2016-03-19
Rev Recd Date: 2016-06-16

Abstract

Objective To systematically evaluate the correlation between selective dipeptidyl peptidase (DPP)-4 inhibitor, vildagliptin and risk of arthralgia/osteoarthritis. Methods The following databases of PubMed (1978 to February 2016), the Cochrane Library (Issue 4, 2015), EMbase (1974 to February 2016), CBM(1978 to February 2016), CNKI(1978 to February 2016), VIP(1989 to February 2016) were searched. The randomized controlled trials (RCTs) for vildagliptin related arthralgia/osteoarthritis were assessed using the Cochrane Collaboration system. The meta-analysis was performed with RevMan 5.3 software. Results Ten RCTs were included. Meta-analysis showed that vildagliptin had higher risk of arthralgia/osteoarthritis than other oral hypoglycemic agents or placebo (RR=1.24, 95%CI 1.08 to 1.44, P=0.003). Further analysis indicated that patients received different doses of vildagliptin had higher risk of arthralgia/osteoarthritis than the placebo group (RR=1.35, 95% CI 1.02 to 1.78, P=0.04). In particular, the group who took vildagliptin 50mg once daily had significantly higher risk of arthralgia/osteoarthritis than the placebo group (RR=3.04, 95%CI 1.44 to 6.44, P=0.004). In comparison of other oral hypoglycemic agents, the vildagliptin group had higher risk of arthralgia/osteoarthritis (RR=1.19, 95% CI 1.01 to 1.41, P=0.04). Conclusion Based on the Meta-analysis results, vildagliptin increases the risk of arthralgia/osteoarthritis. Especially vildagliptin 50mg once daily had two times higher risk than the placebo group. However the long-term safety of vidagliptin still needs to be confirmed by RCTs with larger samples and long term follow-up.
- vildagliptin,
- arthralgia/osteoarthritis,
- risk,
- Meta-analysis

References

[1]	Gu D, Reynolds K,Duan X, et al. Prevalence of diabetes and impaired fasting glucose in the Chinese adult population:international collaborative study of cardiovascular disease in Asia (InterASIA)[J]. Diabetologia, 2003, 46(9):1190-1198.
[2]	Yang W, Liu JM, Weng JP, et al. Prevalence of diabetes among men and women in China[J].N Engl J Med, 2010,362(12):1090-1101.
[3]	Deacon CF, Holst JJ. Dipeptidyl peptidase IV inhibitors:a promising new therapeutic approach for the management of type 2 diabetes[J]. Int J Biochem Cell Biol, 2006, 38(5-6):831-844.
[4]	Ahren B, Landin-Olsson M, Jansson PA, et al. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagon levels in type 2 diabetes[J]. J Clin Endocrinol Metab, 2004, 89(5):2078-2084.
[5]	Mari A, Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed β-cell function in patients with type 2 diabetes[J]. J Clin Endocrinol Metab, 2005,90(8):4888-4894.
[6]	American Diabetes Association. Standards of medical care in diabetes——2015:summary of revisions[J]. Diabetes Care,2015,38(Suppl):S4.
[7]	Hirose T, Suzuki M,Tsumiyama I. Efficacy and safety of vildagliptin as an add-on to insulin with or without metformin in Japanese patients with type 2 diabetes mellitus:a 12-week, double-blind, randomized study[J]. Diabetes Ther,2015,6(4):559-571.
[8]	FDA safety alert. FDA Drug Safety Communication:FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain[EB/OL].[2015-08-28] (2016-02-29).http://www.fda.gov/Drugs/DrugSafety/ucm459579.htm.
[9]	Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0[EB/OL].[2011-03-01] (2016-02-29).http://handbook.cochrane.org/
[10]	CLAF237A2329. A multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF23750 mg bid to 50 mg qd in patients with type 2 diabetes with HbAlc 9-11%[EB/OL].[2007-03-16] (2016-02-29). http://www.novctrd.com/ctrdWebApp/clinicaltrialrepository/displayFile.do?trialResult=2297.
[11]	CLAF237B2224. A multi-center, randomized, double-blind study to evaluate the efficacy and long-term safety of vildagliptin modified release (MR) as add-on therapy to metformin in patients with type 2 diabetes[EB/OL].[2013-09-11] (2016-02-29).http://www.novctrd.com/ctrdWebApp/clinicaltrialrepository/displayFile.do?trialResult=9923.
[12]	Filozof C, Schwartz S, Foley JE. Effect of vildagliptin as add-on therapy to a low-dose metformin[J]. World J Diabetes,2010,1(1):19-26.
[13]	Garber AJ, Schweizer A,Baron MA, et al. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetesfailing thiazolidinedione monotherapy:a randomized, placebo-controlled study[J]. Diabetes Obes Metab, 2007,9(2):166-174.
[14]	Macauley M, Hollingsworth KG, Smith FE, et al. Effect of vildagliptin on hepatic steatosis[J]. J Clin Endocrinol Metab, 2015,100(4):1578-1585.
[15]	Rosenstock J, Niggli M, Maldonado-Lutomirsky M. Long-term 2-year safety and efficacy of vildagliptin compared with rosiglitazone in drug-naïve patients with type 2 diabetes mellitus[J].Diabetes Obes Metab, 2009,11(6):571-578.
[16]	Strain WD, Lukashevich V,Kothny W, et al. Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL):a 24 week, randomised, double-blind, placebo-controlled study[J]. Lancet,2013,382(9890):409-416.
[17]	Scherbaum WA, Schweizer A, Mari A, et al. Evidence that vildagliptin attenuates deterioration of glycaemic control during 2-year treatment of patients with type 2 diabetes and mild hyperglycaemia[J]. Diabetes Obes Metab,2008,10(11):1114-1124.
[18]	Scherbaum WA, Schweizer A, Mari A, et al. Efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia[J]. Diabetes Obes Metab, 2008,10(8):675-682.
[19]	Matthews DR, Dejager S, Ahren B, et al. Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain:results from a 2-year study[J]. Diabetes Obes Metab,2010,12(9):780-789.
[20]	Ospelt C, Mertens JC, Jüngel A, et al. Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial fibroblasts[J]. Arthritis Rheum, 2010,62(5):1224-1235.
[21]	Yan S, Marguet D, Dobers J, et al. Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen[J]. Eur J Immunol,2003,33(6):1519-1527.
[22]	K nig A, Krenn V, Toksoy A, et al. Mig,GRO alpha and RANTES messenger RNA expression in lining layer, infiltrates and different leucocyte populations of synovial tissue from patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis[J]. Virchows Arch,2000,436(5):449-458.
[23]	Loetscher P, Moser B. Homing chemokines in rheumatoid arthritis[J]. Arthritis Res,2002,4(4):233-236.
[24]	Sedo A, Duke-Cohan JS, Balaziova E, et al. Dipeptidyl peptidase IV activity and/or structure homologs:contributing factors in the pathogenesis of rheumatoid arthritis[J]. Arthritis Res Ther,2005,7:253-269.
[25]	Busso N, Wagtmann N, Herling C, et al. Circulating CD26 is negatively associated with inflammation in human and experimental arthritis[J]. Am J Pathol,2005,166(2):433-442.

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A systematic review on the correlation between selective dipeptidyl peptidase inhibitor vildagliptin and risk of arthralgia/osteoarthritis

Department of Pharmacy, No. 180 Hospital of PLA, Quanzhou 362000, China

Received Date: 2016-03-19

Rev Recd Date: 2016-06-16

Key words:

Abstract: Objective To systematically evaluate the correlation between selective dipeptidyl peptidase (DPP)-4 inhibitor, vildagliptin and risk of arthralgia/osteoarthritis. Methods The following databases of PubMed (1978 to February 2016), the Cochrane Library (Issue 4, 2015), EMbase (1974 to February 2016), CBM(1978 to February 2016), CNKI(1978 to February 2016), VIP(1989 to February 2016) were searched. The randomized controlled trials (RCTs) for vildagliptin related arthralgia/osteoarthritis were assessed using the Cochrane Collaboration system. The meta-analysis was performed with RevMan 5.3 software. Results Ten RCTs were included. Meta-analysis showed that vildagliptin had higher risk of arthralgia/osteoarthritis than other oral hypoglycemic agents or placebo (RR=1.24, 95%CI 1.08 to 1.44, P=0.003). Further analysis indicated that patients received different doses of vildagliptin had higher risk of arthralgia/osteoarthritis than the placebo group (RR=1.35, 95% CI 1.02 to 1.78, P=0.04). In particular, the group who took vildagliptin 50mg once daily had significantly higher risk of arthralgia/osteoarthritis than the placebo group (RR=3.04, 95%CI 1.44 to 6.44, P=0.004). In comparison of other oral hypoglycemic agents, the vildagliptin group had higher risk of arthralgia/osteoarthritis (RR=1.19, 95% CI 1.01 to 1.41, P=0.04). Conclusion Based on the Meta-analysis results, vildagliptin increases the risk of arthralgia/osteoarthritis. Especially vildagliptin 50mg once daily had two times higher risk than the placebo group. However the long-term safety of vidagliptin still needs to be confirmed by RCTs with larger samples and long term follow-up.

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Reference (25)

[1]	Gu D, Reynolds K,Duan X, et al. Prevalence of diabetes and impaired fasting glucose in the Chinese adult population:international collaborative study of cardiovascular disease in Asia (InterASIA)[J]. Diabetologia, 2003, 46(9):1190-1198.
[2]	Yang W, Liu JM, Weng JP, et al. Prevalence of diabetes among men and women in China[J].N Engl J Med, 2010,362(12):1090-1101.
[3]	Deacon CF, Holst JJ. Dipeptidyl peptidase IV inhibitors:a promising new therapeutic approach for the management of type 2 diabetes[J]. Int J Biochem Cell Biol, 2006, 38(5-6):831-844.
[4]	Ahren B, Landin-Olsson M, Jansson PA, et al. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagon levels in type 2 diabetes[J]. J Clin Endocrinol Metab, 2004, 89(5):2078-2084.
[5]	Mari A, Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed β-cell function in patients with type 2 diabetes[J]. J Clin Endocrinol Metab, 2005,90(8):4888-4894.
[6]	American Diabetes Association. Standards of medical care in diabetes——2015:summary of revisions[J]. Diabetes Care,2015,38(Suppl):S4.
[7]	Hirose T, Suzuki M,Tsumiyama I. Efficacy and safety of vildagliptin as an add-on to insulin with or without metformin in Japanese patients with type 2 diabetes mellitus:a 12-week, double-blind, randomized study[J]. Diabetes Ther,2015,6(4):559-571.
[8]	FDA safety alert. FDA Drug Safety Communication:FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain[EB/OL].[2015-08-28] (2016-02-29).http://www.fda.gov/Drugs/DrugSafety/ucm459579.htm.
[9]	Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0[EB/OL].[2011-03-01] (2016-02-29).http://handbook.cochrane.org/
[10]	CLAF237A2329. A multicenter, double-blind, randomized, active controlled, parallel group study to compare the effect of 12 weeks treatment with LAF23750 mg bid to 50 mg qd in patients with type 2 diabetes with HbAlc 9-11%[EB/OL].[2007-03-16] (2016-02-29). http://www.novctrd.com/ctrdWebApp/clinicaltrialrepository/displayFile.do?trialResult=2297.
[11]	CLAF237B2224. A multi-center, randomized, double-blind study to evaluate the efficacy and long-term safety of vildagliptin modified release (MR) as add-on therapy to metformin in patients with type 2 diabetes[EB/OL].[2013-09-11] (2016-02-29).http://www.novctrd.com/ctrdWebApp/clinicaltrialrepository/displayFile.do?trialResult=9923.
[12]	Filozof C, Schwartz S, Foley JE. Effect of vildagliptin as add-on therapy to a low-dose metformin[J]. World J Diabetes,2010,1(1):19-26.
[13]	Garber AJ, Schweizer A,Baron MA, et al. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetesfailing thiazolidinedione monotherapy:a randomized, placebo-controlled study[J]. Diabetes Obes Metab, 2007,9(2):166-174.
[14]	Macauley M, Hollingsworth KG, Smith FE, et al. Effect of vildagliptin on hepatic steatosis[J]. J Clin Endocrinol Metab, 2015,100(4):1578-1585.
[15]	Rosenstock J, Niggli M, Maldonado-Lutomirsky M. Long-term 2-year safety and efficacy of vildagliptin compared with rosiglitazone in drug-naïve patients with type 2 diabetes mellitus[J].Diabetes Obes Metab, 2009,11(6):571-578.
[16]	Strain WD, Lukashevich V,Kothny W, et al. Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL):a 24 week, randomised, double-blind, placebo-controlled study[J]. Lancet,2013,382(9890):409-416.
[17]	Scherbaum WA, Schweizer A, Mari A, et al. Evidence that vildagliptin attenuates deterioration of glycaemic control during 2-year treatment of patients with type 2 diabetes and mild hyperglycaemia[J]. Diabetes Obes Metab,2008,10(11):1114-1124.
[18]	Scherbaum WA, Schweizer A, Mari A, et al. Efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia[J]. Diabetes Obes Metab, 2008,10(8):675-682.
[19]	Matthews DR, Dejager S, Ahren B, et al. Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain:results from a 2-year study[J]. Diabetes Obes Metab,2010,12(9):780-789.
[20]	Ospelt C, Mertens JC, Jüngel A, et al. Inhibition of fibroblast activation protein and dipeptidylpeptidase 4 increases cartilage invasion by rheumatoid arthritis synovial fibroblasts[J]. Arthritis Rheum, 2010,62(5):1224-1235.
[21]	Yan S, Marguet D, Dobers J, et al. Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen[J]. Eur J Immunol,2003,33(6):1519-1527.
[22]	K nig A, Krenn V, Toksoy A, et al. Mig,GRO alpha and RANTES messenger RNA expression in lining layer, infiltrates and different leucocyte populations of synovial tissue from patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis[J]. Virchows Arch,2000,436(5):449-458.
[23]	Loetscher P, Moser B. Homing chemokines in rheumatoid arthritis[J]. Arthritis Res,2002,4(4):233-236.
[24]	Sedo A, Duke-Cohan JS, Balaziova E, et al. Dipeptidyl peptidase IV activity and/or structure homologs:contributing factors in the pathogenesis of rheumatoid arthritis[J]. Arthritis Res Ther,2005,7:253-269.
[25]	Busso N, Wagtmann N, Herling C, et al. Circulating CD26 is negatively associated with inflammation in human and experimental arthritis[J]. Am J Pathol,2005,166(2):433-442.

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A systematic review on the correlation between selective dipeptidyl peptidase inhibitor vildagliptin and risk of arthralgia/osteoarthritis

doi: 10.3969/j.issn.1006-0111.2016.06.015

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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