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Efficacy and tolerability of DPP4 inhibitor, teneligliptin, on autonomic and peripheral neuropathy in type 2 diabetes: an open label, pilot study

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Abstract

Background

Diabetic neuropathy increases risk of cardiovascular disease, peripheral artery disease, foot amputation and overall mortality. Not only hyperglycaemia induced nerve damage is harder to repair using currently approved medications, but also, the use of these agents is often limited by the extent of pain relief provided and side effects.

Methodology

In this prospective, open-label, pilot study, 20 type-2 diabetes mellitus patients (male/female=13/7, mean age- 56.1±8.04 years), meeting inclusion/exclusion criteria, were treated with dipeptidyl peptidase-4 (DPP-4) inhibitor, Teneligliptin, 20mg once a day for three months. Efficacy parameters: Sudomotor function (Sudoscan score); parasympathetic dysfunction assessed using Ewing’s criteria i.e. heart rate response to –standing (HRS), -valsalva (HRV) and -deep breath (HRD); sympathetic dysfunction assessed as blood pressure response to -standing (BPS) and –handgrip (BPH); ankle brachial index (ABI), vibration perception threshold (VPT), C-reactive protein, glycemic profile and health related quality of life (HRQoL); and, tolerability parameters: complete blood count, liver function tests, serum creatinine, thyroid stimulating hormone, QT- interval and serum vitamin B12 levels, were measured.

Results

There was no statistical difference in BMI, SBP, DBP, HRD, BPH and all safety parameters. After 12 weeks treatment, there was improvement in HRS (p<0.01) and HRV (p<0.01), but not in HRD (p=0.12). BPS was significantly lowered (p <0.01), but not the BPH (p =0.06). Sudoscan score was increased, while VPT was significantly decreased (both p<0.01).

Conclusion

Teneligliptin not only improves the glycemic status but also improves sudomotor function, peripheral and autonomic neuropathy, and reduces vascular inflammation in type 2 diabetes.

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References

  1. Ricci L, Luigetti M, Florio L, Capone F, Di Lazzaro V (2019) Causes of chronic neuropathies: a single-center experience. Neurol Sci 40:1611–1617. https://doi.org/10.1007/s10072-019-03899-z

    Article  PubMed  Google Scholar 

  2. Paul DA, Qureshi ARM, Rana AQ (2020) Peripheral neuropathy in Parkinson's disease. Neurol Sci. https://doi.org/10.1007/s10072-020-04407-4

  3. Kreymann B, Williams G, Ghatei MA, Bloom SR (1987) Glucagon-like peptide-1, a physiological incretin in man. Lancet 2:1300–1304. https://doi.org/10.1016/S0140-6736(87)91194-9

    Article  CAS  PubMed  Google Scholar 

  4. Perry T, Lahiri DK, Chen D, Zhou J, Shaw KT, Egan JM et al (2002) A novel neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth factor-mediated differentiation in PC12 cells. J Pharmacol Exp Ther 300:958–966. https://doi.org/10.1124/jpet.300.3.958

    Article  CAS  PubMed  Google Scholar 

  5. Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig NH (2007) Evidence of GLP-1-mediated neuro protection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 203:293–301. https://doi.org/10.1016/j.expneurol.2006.09.028

    Article  CAS  PubMed  Google Scholar 

  6. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ et al (1995) Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 44:1126–1131. https://doi.org/10.2337/diab.44.9.1126

    Article  CAS  PubMed  Google Scholar 

  7. Holst JJ, Deacon CF (1998) Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes 47:1663–1670. https://doi.org/10.2337/diabetes.47.11.1663

    Article  CAS  PubMed  Google Scholar 

  8. Jin HY, Liu WJ, Park JH, Baek HS, Park TS (2009) Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor (Vildagliptin) on peripheral nerves in streptozotocin-induced diabetic rats. Arch Med Res 40:536–544. https://doi.org/10.1016/j.arcmed.2009.09.005

    Article  CAS  PubMed  Google Scholar 

  9. Davidson EP, Coppey LJ, Dake B, Yorek MA (2011) Treatment of streptozotocin-induced diabetic rats with alogliptin: effect on vascular and neural complications. Exp Diabetes Res 2011:810469–810467. https://doi.org/10.1155/2011/810469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Syngle A, Verma I, Krishan P, Garg N, Syngle V (2014) Minocycline improves peripheral and autonomic neuropathy in type 2 diabetes: MIND study. Neurol Sci 35:1067–1073. https://doi.org/10.1007/s10072-014-1647-2

    Article  PubMed  Google Scholar 

  11. Bagherzadeh Cham M, Mohseni-Bandpei MA, Bahramizadeh M, Kalbasi S, Biglarian A (2018) The effects of vibro-medical insole on vibrotactile sensation in diabetic patients with mild-to-moderate peripheral neuropathy. Neurol Sci 39:1079–1084. https://doi.org/10.1007/s10072-018-3318-1

    Article  PubMed  Google Scholar 

  12. Basantsova NY, Starshinova AA, Dori A, Zinchenko YS, Yablonskiy PK, Shoenfeld Y (2019) Small-fiber neuropathy definition, diagnosis, and treatment. Neurol Sci 40:1343–1350. https://doi.org/10.1007/s10072-019-03871-x

    Article  PubMed  Google Scholar 

  13. Otsuki H, Kosaka T, Nakamura K, Shimomura F, Kuwahara Y, Tsukamoto T (2014) Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis patients with type 2 diabetes. Int Urol Nephrol 46:427–432. https://doi.org/10.1007/s11255-013-0552-6

    Article  CAS  PubMed  Google Scholar 

  14. Hashikata T, Yamaoka-Tojo M, Kakizaki R, Nemoto T, Fujiyoshi K, Namba S, Kitasato L, Hashimoto T, Kameda R, Maekawa E, Shimohama T, Tojo T, Ako J (2016) Teneligliptin improves left ventricular diastolic function and endothelial function in patients with diabetes. Heart Vessel 31:1303–1310. https://doi.org/10.1007/s00380-015-0724-7

    Article  Google Scholar 

  15. Tsuchimochi W, Ueno H, Yamashita E, Tsubouchi C, Sakoda H, Nakamura S, Nakazato M (2015) Teneligliptin improves glycemic control with the reduction of postprandial insulin requirement in Japanese diabetic patients. Endocr J 62:13–20. https://doi.org/10.1507/endocrj.EJ14-039

    Article  CAS  PubMed  Google Scholar 

  16. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R (2005) Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 28:956–962. https://doi.org/10.2337/diacare.28.4.956

    Article  PubMed  Google Scholar 

  17. Ewing DJ, Clarke BF (1986) Autonomic neuropathy: its diagnosis and prognosis. Clin Endocrinol Metab 15:855–888. https://doi.org/10.1016/S0300-595X(86)80078-0

    Article  CAS  PubMed  Google Scholar 

  18. Zilliox L, Peltier AC, Wren PA, Anderson A, Smith AG, Singleton JR, Feldman EL, Alexander NB, Russell JW (2001) Assessing autonomic dysfunction in early diabetic neuropathy: the survey of autonomic symptoms. Neurology 76:1099–1105. https://doi.org/10.1212/WNL.0b013e3182120147

    Article  Google Scholar 

  19. Garrow AP, Boulton AJ (2006) Vibration perception threshold—a valuable assessment of neural dysfunction in people with diabetes. Diabetes Metab Res Rev 22:411–419. https://doi.org/10.1002/dmrr.657

    Article  PubMed  Google Scholar 

  20. Williams G, Gill JS, Aber V, Mather HM (1988) Variability in vibration perception threshold among sites: a potential source of error in biothesiometry. Br Med J (Clin Res Ed) 296:233–235

    Article  CAS  Google Scholar 

  21. Mayaudon H, Miloche PO, Bauduceau B (2010) A new simple method for assessing sudomotor function: relevance in type 2 diabetes. Diabetes Metab 36:450–454. https://doi.org/10.1016/j.diabet.2010.05.004

    Article  CAS  PubMed  Google Scholar 

  22. Kumar A, Malaviya AN, Pandhi A, Singh R (2002) Validation of an Indian version of the health assessment questionnaire in patients with rheumatoid arthritis. Rheumatology (Oxford) 41:1457–1459. https://doi.org/10.1093/rheumatology/41.12.1457

    Article  CAS  Google Scholar 

  23. Kishimoto M (2013) Teneligliptin: a DPP-4 inhibitor for the treatment of type 2 diabetes. Diabetes Metab Syndr Obes 6:187–195. https://doi.org/10.2147/DMSO.S35682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Goldenberg IL, Moss AJ, Zareba W (2006) QT interval: how to measure it and what is" normal". J Cardiovasc Electrophysiol 17:333–336. https://doi.org/10.1111/j.1540-8167.2006.00408.x

    Article  PubMed  Google Scholar 

  25. Kadowaki T, Kondo K (2014) Efficacy and safety of teneligliptin added to glimepiride in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study with an open-label, long-term extension. Diabetes Obes Metab 16:418–425. https://doi.org/10.1111/dom.12235

    Article  CAS  PubMed  Google Scholar 

  26. Kadowaki T, Kondo K (2013) Efficacy, safety and dose–response relationship of teneligliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus. Diabetes Obes Metab 15:810–818. https://doi.org/10.1111/dom.12092

    Article  CAS  PubMed  Google Scholar 

  27. Kim MK, Rhee EJ, Han KA, Woo AC, Lee MK, Ku BJ, Chung CH, Kim KA, Lee HW, Park IB, Park JY, Chul Jang HC, Park KS, Jang WI, Cha BY (2015) Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week randomized, double-blind, placebo-controlled phase III trial. Diabetes Obes Metab 17:309–312. https://doi.org/10.1111/dom.12424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Maser RE, James Lenhard M, Pohlig RT, Babu Balagopal P (2017) Osteopontin and clusterin levels in type 2 diabetes mellitus: differential association with peripheral autonomic nerve function. Neurol Sci 38:1645–1650. https://doi.org/10.1007/s10072-017-3019-1

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M, Toyota T, Nakashima M, Yoshimura I, Sakamoto N, Shigeta Y (2006) Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative aldose reductase inhibitor-diabetes complications trial. Diabetes Care 29:1538–1544. https://doi.org/10.2337/dc05-2370

    Article  CAS  PubMed  Google Scholar 

  30. Kumthekar AA, Gidwani HV, Kumthekar AB (2012) Metformin associated B12 deficiency. J Assoc Physicians India 60:58–60

    PubMed  Google Scholar 

  31. Hijazi MM, Buchmann SJ, Sedghi A, Illigens BM, Reichmann H, Schackert G, Siepmann T (2020) Assessment of cutaneous axon-reflex responses to evaluate functional integrity of autonomic small nerve fibers. Neurol Sci 2020:1685–1696. https://doi.org/10.1007/s10072-020-04293-w

    Article  Google Scholar 

  32. Rennings A, Smits P, Stewart M, Tack C (2010) Autonomic neuropathy predisposes to rosiglitazone-induced vascular leakage in insulin-treated patients with type 2 diabetes: a randomised, controlled trial on thiazolidinedione-induced vascular leakage. Diabetologia 53:1856–1866. https://doi.org/10.1007/s00125-010-1787-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schütte KL et al (1999) Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III study). ALADIN III study group. Alpha-lipoic acid in diabetic neuropathy. Diabetes Care 22:1296–1301. https://doi.org/10.2337/diacare.22.8.1296

    Article  CAS  PubMed  Google Scholar 

  34. Lobinet E, Reichardt F, Garret C, Cazals L, Waget A, Dejajer S et al (2015) Autonomic diabetic neuropathy impaired glucose and dipeptidyl peptidase 4 inhibitor-regulated glucagon concentration in type 1 diabetic patients. J Endocrinol Metab 5:229–237. https://doi.org/10.14740/jem289w

    Article  CAS  Google Scholar 

  35. Martin CL, Waberski BH, Pop-Busui R, Cleary PA, Catton S, Albers JW, Feldman EL, Herman WH, on behalf of the DCCT/EDIC Research Group (2010) Vibration perception threshold as a measure of distal symmetrical peripheral neuropathy in type 1 diabetes: results from the DCCT/EDIC study. Diabetes Care 33:2635–2641. https://doi.org/10.2337/dc10-0616

    Article  PubMed  PubMed Central  Google Scholar 

  36. Chahal S, Vohra K, Syngle A (2017) Association of sudomotor function with peripheral artery disease in type 2 diabetes. Neurol Sci 38:151–156. https://doi.org/10.1007/s10072-016-2742-3

    Article  PubMed  Google Scholar 

  37. Casellini CM, Parson HK, Richardson MS, Nevoret ML, Vinik AI (2013) Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction. Diabetes Technol Ther 15:948–953. https://doi.org/10.1089/dia.2013.0129

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kanchan V, Pawan K, Sudhir V, Singh KH (2016) Effect of low-dose mineralocorticoid receptor antagonists on metabolic profile and endothelial dysfunction in metabolic syndrome. Diabetes Metab 42:65–68. https://doi.org/10.1016/j.diabet.2015.10.005

    Article  CAS  PubMed  Google Scholar 

  39. Huzmeli ED, Melek I (2017) Neuropathic pain’s biopsychosocial effects. Neurol Sci 38(11):1993–1997. https://doi.org/10.1007/s10072-017-3092-5

    Article  Google Scholar 

  40. Levterova B, Naydenov V, Todorov P, Leterov G (2018) Prevalence and impact of peripheral neuropathy on quality of life in patients with diabetes mellitus pilot study. Trakia J Sci 16(1):71–76. https://doi.org/10.15547/tjs.2018.s.01.015

    Article  Google Scholar 

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Acknowledgements

We gratefully acknowledge academic contribution of Mr. Balkar Chand, Research Scholar, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, in preparing the manuscript.

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Authors and Affiliations

  1. Healing Touch City Clinic, # 547, Sector 16-D, Chandigarh, India

    Ashit Syngle

  2. Fortis Multi Specialty Hospital, Mohali, Punjab, India

    Ashit Syngle

  3. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India

    Simran Chahal & Kanchan Vohra

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  1. Ashit Syngle
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Correspondence to Kanchan Vohra.

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The study was approved by the Institutional Ethics Committee (IEC) (approval no: 61), Punjabi University, Patiala, and was conducted in accordance with “Ethical guidelines for biomedical research on human participants” issued by Indian Council of Medical Research (ICMR).

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Syngle, A., Chahal, S. & Vohra, K. Efficacy and tolerability of DPP4 inhibitor, teneligliptin, on autonomic and peripheral neuropathy in type 2 diabetes: an open label, pilot study. Neurol Sci 42, 1429–1436 (2021). https://doi.org/10.1007/s10072-020-04681-2

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