Official Journal of the College of Pharmacy, University of Mosul

Document Type : Review Paper

Authors

1 Nineveh Health Directorate, Ministry of Health, Mosul, Iraq

2 Department of Pharmacology and Toxicology, College of Medicine, University of Mosul, Iraq

Abstract

Background: Cilnidipine, a common hypertension medication, is now being studied for its potential to improve insulin sensitivity, which plays a key role in regulating blood sugar levels. Recent research suggests that cilnidipine may benefit individuals with both hypertension and insulin resistance, offering a promising avenue for further investigation and potential therapeutic applications. Objective: The present study aimed to investigate the influence of cilnidipine on insulin sensitivity, seeking to comprehend how this medication affects the body's capacity to utilize insulin efficiently. Methods: The current literature search was conducted using diverse databases, primarily including PubMed, Elsevier, Google Scholar, and the Iraqi Virtual Science Library. The search was limited to publications up to [2009-2023], and the keywords "Cilnidipine" and "Insulin Sensitivity" were used to identify relevant articles. Inclusion and exclusion criteria were applied to filter the search results, and the number of papers retrieved meeting these criteria was recorded for further analysis. Results: indicate that cilnidipine may have a positive impact on insulin sensitivity in individuals with hypertension and type 2 diabetes. This suggests that cilnidipine could potentially be a beneficial therapeutic option for addressing insulin resistance in these patients. However, it is crucial to note that further research is necessary to confirm these findings and evaluate the long-term effects of cilnidipine on insulin sensitivity. Conclusion: The results of this study indicate a potential positive impact of cilnidipine on insulin sensitivity in individuals with both hypertension and type 2 diabetes. This suggests that cilnidipine could serve as a promising therapeutic option for addressing insulin resistance in these patients.

Keywords

Main Subjects

  1. Zhao H, Zhang J, Cheng X, Nie X, He B. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment. Journal of Ovarian Research. 2023;16(1):1-17.
  2. Stanciu S, Rusu E, Miricescu D, Radu AC, Axinia B, Vrabie AM, et al. Links between Metabolic Syndrome and Hypertension: The Relationship with the Current Antidiabetic Drugs. Metabolites. 2023;13(1):87.
  3. Succurro E, Cicone F, Papa A, Miceli S, Vizza P, Fiorentino TV, et al. Impaired insulin-stimulated myocardial glucose metabolic rate is associated with reduced estimated myocardial energetic efficiency in subjects with different degrees of glucose tolerance. Cardiovascular Diabetology. 2023;22(1):1-11.
  4. Stowasser M, Jansen P, Wolley M. Systematic approach to the diagnosis and management of endocrine hypertension. In: Endocrine Hypertension. Elsevier; 2023:331-368.
  5. Masuda T, Ogura MN, Moriya T, Takahira N, Matsumoto T, Kutsuna T, et al. Beneficial Effects of L‐and N‐type Calcium Channel Blocker on Glucose and Lipid Metabolism and Renal Function in Patients with Hypertension and Type II Diabetes Mellitus. Cardiovascular therapeutics. 2011;29(1):46-53.
  6. Guthrie RM, Lott JA. Screening for proteinuria in patients with hypertension or diabetes mellitus. Journal of family practice. 1993;37:253.
  7. Varadi G, Mori Y, Mikala G, Schwartz A. Molecular determinants of Ca2+ channel function and drug action. Trends in pharmacological sciences. 1995;16(2):43-49.
  8. Takahara A. Cilnidipine: a new generation Ca2+ channel blocker with inhibitory action on sympathetic neurotransmitter release. Cardiovascular therapeutics. 2009;27(2):124-139.
  9. Chakraborty RN, Langade D, More S, Revandkar V, Birla A, Langade DG, et al. Efficacy of Cilnidipine (L/N-type Calcium Channel Blocker) in Treatment of Hypertension: A Meta-Analysis of Randomized and Non-randomized Controlled Trials. Cureus. 2021;13(11).
  10. Harada E, Sugino K, Aimoto M, Takahara A. Effects of the L/N-Type Ca(2+) Channel Blocker Cilnidipine on the Cardiac Histological Remodelling and Inducibility of Atrial Fibrillation in High-Salt-Fed Rats. Biological & pharmaceutical bulletin. 2021;44(5):707-713.
  11. Shete MM. Cilnidipine: Next generation calcium channel blocker. Journal of Association of Physicians of India. 2016;64(APRIL):95-99.
  12. Chandra KS, Ramesh G. The fourth-generation Calcium channel blocker: Cilnidipine. Indian heart journal. 2013;65(6):691-695.
  13. Das A, Kumar P, Kumari A, Chandra S, Gari M, Singh N, et al. Effects of cilnidipine on heart rate and uric acid metabolism in patients with essential hypertension. Cardiology Research. 2016;7(5):167.
  14. Tripathy D, Carlsson M, Almgren P, Isomaa B, Taskinen MR, Tuomi T, et al. Insulin secretion and insulin sensitivity in relation to glucose tolerance: lessons from the Botnia Study. Diabetes. 2000;49(6):975-980.
  15. Kalil GZ, Haynes WG. Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. Hypertension Research. 2012;35(1):4-16.
  16. Takahashi E, Ito M, Miyamoto N, Nagasu T, Ino M, Tanaka I. Increased glucose tolerance in N-type Ca2+ channel alpha(1B)-subunit gene-deficient mice. International journal of molecular medicine. 2005;15(6):937-944.
  17. Haap M, Heller E, Thamer C, Tschritter O, Stefan N, Fritsche A. Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects. European journal of clinical nutrition. 2006;60(6):734-739.
  18. Prasanna G. Formulation Development and Evaluation of Cilnidipine Nanosuspension for the treatment of Hypertension using Anti-Solvent Precipitation and Ultrasonication Method. 2021.
  19. Kali MSK, Khan MRI, Barman RK, Hossain MF, Wahed MII. Cilnidipine and magnesium sulfate supplement ameliorates hyperglycemia, dyslipidemia and inhibits oxidative-stress in fructose-induced diabetic rats. Heliyon. 2022;8(1).
  20. Siddiqui MMR, Mosharraf SSB, Giasuddin RS, Islam N, Mirza S. What is new in new generation calcium channel blocker. Anwer Khan Modern Medical College Journal. 2019;10(1):77-83.
  21. Onose Y, Oki T, Yamada H, Manabe K, Kageji Y, Matsuoka M, et al. Effect of cilnidipine on left ventricular diastolic function in hypertensive patients as assessed by pulsed Doppler echocardiography and pulsed tissue Doppler imaging. Japanese circulation journal. 2001;65(4):305-309.
  22. Ikejder Y, Sebbani M, Hendy I, Khramz M, Khatouri A, Bendriss L. Impact of arterial hypertension on left atrial size and function. BioMed Research International. 2020;2020.
  23. Shete MM. Cilnidipine: next generation calcium channel blocker. J Assoc Physicians India. 2016;64(4):95-99.
  24. Sakata K, Yoshida H, Tamekiyo H, Obayashi K, Nawada R, Mori N. Comparative effect of clinidipine and quinapril on left ventricular mass in mild essential hypertension. Drugs under experimental and clinical research. 2003;29(3):117-123.
  25. Ahmed SN, Jhaj R, Sadasivam B, Joshi R. Regression of the left ventricular hypertrophy in patients with essential hypertension on standard drug therapy. Discoveries. 2020;8(3).
  26. Burnier M, Damianaki A. Hypertension as cardiovascular risk factor in chronic kidney disease. Circulation Research. 2023;132(8):1050-1063.
  27. Weldegiorgis M, Woodward M. The impact of hypertension on chronic kidney disease and end-stage renal disease is greater in men than women: a systematic review and meta-analysis. BMC nephrology. 2020;21(1):1-9.
  28. Provenzano M, Coppolino G, Faga T, Garofalo C, Serra R, Andreucci M. Epidemiology of cardiovascular risk in chronic kidney disease patients: the real silent killer. Reviews in cardiovascular medicine. 2019;20(4):209-220.
  29. Dane MJC, van den Berg BM, Avramut MC, Faas FGA, van der Vlag J, Rops AL, et al. Glomerular endothelial surface layer acts as a barrier against albumin filtration. The American journal of pathology. 2013;182(5):1532-1540
  30. Anil Kumar P, Welsh GI, Saleem MA, Menon RK. Molecular and cellular events mediating glomerular podocyte dysfunction and depletion in diabetes mellitus. Frontiers in endocrinology. 2014;5:151.
  31. Trimarchi H. Mechanisms of podocyte detachment, podocyturia, and risk of progression of glomerulopathies. Kidney Diseases. 2020;6(5):324-329.
  32. Benzing T, Salant D. Insights into glomerular filtration and albuminuria. New England Journal of Medicine. 2021;384(15):1437-1446.
  33. Kumari K, Sinha R, Toppo MS, Mishra P, Alam S, Majhee L, et al. Blood Pressure Reducing Potential and Renoprotective Action of Cilnidipine Among Hypertensive Patients Suffering From Chronic Kidney Disease: A Meta-Analysis. Cureus. 2023;15(4).
  34. Rysz J, Banach M, Franczyk B, Gluba-Brzózka A. Novel strategies of hypertension management in chronic kidney disease. Archives of Medical Science. 2021;17(6).
  35. Zhao M, Zhang Z, Pan Z, Ma S, Chang M, Fan J, et al. N-/T-Type vs. L-Type Calcium Channel Blocker in Treating Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel, Switzerland). 2023;16(3).
  36. Fujita T, Ando K, Nishimura H, Ideura T, Yasuda G, Isshiki M, et al. Antiproteinuric effect of the calcium channel blocker cilnidipine added to renin-angiotensin inhibition in hypertensive patients with chronic renal disease. Kidney international. 2007;72(12):1543-1549.
  37. Adake P, Somashekar HS, Rafeeq PKM, Umar D, Basheer B, Baroudi K. Comparison of amlodipine with cilnidipine on antihypertensive efficacy and incidence of pedal edema in mild to moderate hypertensive individuals: A prospective study. Journal of advanced pharmaceutical technology & research. 2015;6(2):81.
  38. Li M, Yuan N, Nurnberger JI, Alliey-Rodriguez N, Zhou J, Duan F, et al. A pilot pharmacogenetic study of calcium channel blocker treatment of bipolar mania. Psychiatry Research. 2023:115281.
  39. Shetty K, Shetty R, Bairy L, Rao P, Kiran A, Shetty M, et al. A Comparative Study on Clinical and Biochemical Parameters in Amlodipine and Cilnidipine Treated Hypertensive Patients. Journal of clinical and diagnostic research: JCDR. 2017;11(5):FC01-FC05.
  40. Little HJ. L-type calcium channel blockers: A potential novel therapeutic approach to drug dependence. Pharmacological Reviews. 2021;73(4):1298-1325.
  41. Godfraind T. Discovery and development of calcium channel blockers. Frontiers in pharmacology. 2017;8:286.
  42. Aritomi S, Niinuma K, Ogawa T, Konda T, Nitta K. Effects of an N-type calcium antagonist on angiotensin II-renin feedback. American Journal of Nephrology. 2011;33(2):168-175.
  43. Bulsara KG, Cassagnol M. Amlodipine. In: StatPearls [Internet]. StatPearls Publishing; 2022.