Effect of losartan and amlodipine on insulin sensitivity in non-diabetic hypertensive patients

Authors

  • Sandesh M. Bharati Department of Pharmacology, SMBT Institute of Medical Sciences and Research Centre, Dhamangaon, Nashik, Maharashtra, India
  • Nishith Singh Department of Pharmacology, Armed Forces Medical College, Pune, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20160128

Keywords:

Hypertension, Insulin resistance, Losartan, Amlodipine

Abstract

Background: Hypertensive patients show higher insulin levels than normotensive controls. Hypertension is linked to impaired glucose tolerance and resistance to the action of insulin. Untreated hypertensive patients are at risk of developing new onset diabetes mellitus. Different antihypertensive drugs affect the insulin sensitivity distinctly. Few studies have demonstrated the beneficial effects of losartan, an angiotensin receptor blocker on the glucose insulin metabolism, but other studies have failed to demonstrate the insulin resistance lowering effect of losartan. Amlodipine, a long acting calcium channel blocker is considered to have neutral effects on the glucose-insulin metabolism.

Methods: In a prospective, open-label, parallel group study, non-diabetic patients with mild to moderate hypertension were randomized to either losartan (titrated from 50 to 100 mg /day, n=20) or amlodipine (titrated from 5 to 10 mg/ day, n=20) for period of 24 weeks. At baseline, 12 weeks and 24 weeks fasting plasma glucose, fasting plasma insulin, homeostasis model assessment for insulin resistance (HOMA-IR) apart from lipid parameters, mean systolic and diastolic blood pressures levels were determined.

Results: Intragroup comparison shows that both losartan and amlodipine significantly reduced the HOMA-IR index (P < 0.05, 24 weeks vs. baseline). Losartan reduced HOMA-IR more than amlodipine but this reduction was not statistically significant.

Conclusions: Losartan and amlodipine lowered insulin resistance in patients of mild to moderate hypertension.

References

Blackburn DF, Wilson TW. Antihypertensive medications and blood sugar: Theories and implications. Can J Cardiol. 2006;22(3):229-33.

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-52.

Taylor EN, Hu FB, Curhan GC. Antihypertensive medications and the risk of incident type 2 diabetes. Diabetes Care. 2006;29(5):1065-70.

Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension 2001; 37(4):1053-9.

Fukao K, Shimada K, Hiki M, Kiyanagi MT, Hirose K, Kume A, et al. Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT). Cardiovasc Diabetol. 2011;10:79.

Kurtz TW, Pravenec M. Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin angiotensin system. J Hypertens. 2004; 22(12):2253-61.

Igarashi M, Hirata A, Kadomoto Y, Tominaga M. Dual blockade of angiotensin II with enalapril and losartan reduces proteinuria in hypertensive patients with type 2 diabetes. Endocr J. 2006;53(4):493-501.

Moan A, Hoieggen A, Seljeflot I, Risanger T, Arnesen H, Kjeldsen SE. The effect of angiotensin II receptor antagonism with losartan on glucose metabolism and insulin sensitivity. J Hypertens. 1996;14(9):1093-7.

Moan A, Hoieggen A, Nordby G, Eide K, Kjeldsen SE. Effects of losartan on insulin sensitivity in severe hypertension: connections through sympathetic nervous system activity. J Human Hypertension. 1995;9(Suppl 5):S45-50.

Siegel D, Swislocki ALM. Effects of antihypertensives on glucose metabolism. Metab Syndr Relat Disord. 2007;5(3):211-9.

Ersoy C, Imamoglu S, Budak F, Tuncel E, Erturk E, Oral B. Effect of amlodipine on insulin resistance & tumor necrosis factor-alpha levels in hypertensive obese type 2 diabetic patients. Indian J Med Res. 2004;120(5):481-8.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.

Radikova Z. Assessment of insulin sensitivity/resistance in epidemiological studies. Endocr Regul. 2003;37(3):189-94.

Jin HM, Pan Y. Angiotensin type-1 receptor blockade with losartan increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetes and nephropathy. Nephrol Dial Transplant. 2007;22(7):1943-9.

Aksnes TA, Seljeflot I, Torjesen PA, Hoieggen A, Moan A, Kjeldsen SE. Improved insulin sensitivity by the angiotensin II-receptor blocker losartan is not explained by adipokines inflammatory markers, or whole blood viscosity. Metab Clin Exper. 2007;56(11):1470-7.

Nishimura H, Sanaka T, Tanihata Y, Naito T, Higuchi C, Otsuka K. Losartan elevates the serum high-molecular weight-adiponectin isoform and concurrently improves insulin sensitivity in patients with impaired glucose metabolism. Hypertens Res. 2008;31(8):1611-8.

Morisco C, Trimarco B. Insulin resistance and hypertension: the link. Hot Topics in Hypertension. 2008;2:7-20.

Velloso LA, Folli F, Sun XJ, White MF, Saad MJ, Kahn CR. Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci USA. 1996;93:12490-5.

Shiuchi T, Iwai M, Li HS, Wu L, Min LJ, Li JM, et al. Angiotensin II type-1 receptor blocker valsartan enhances insulin sensitivity in skeletal muscles of diabetic mice. Hypertension. 2004;43(5):1003-10.

Bahadir O, Uzunlulu M, Oguz A, Bahadir MA. Effects of telmisartan and losartan on insulin resistance in hypertensive patients with metabolic syndrome. Hypertens Res. 2007;30(1):49-53.

Yavuz D, Koc M, Toprak A, Akpinar I, Velioglu A, Deyneli O, et al. Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients. J Renin Angiotensin Aldosterone Syst. 2003;4(3):197-203.

Huang GZ, Tang YH, Wang BY, Zhang B, Hu TJ, Zhang L, et al. Effects of telmisartan on insulin resistance and visceral fat distribution in Chinese hypertensive patients with obesity. Saudi Med J. 2011;32(10):1017-21.

Perl S, Schmölzer I, Sourij H, Pressl H, Eder M, Zweiker R, et al. Telmisartan improves vascular function independently of metabolic and antihypertensive effects in hypertensive subjects with impaired glucose tolerance. Int J Cardiol. 2010;139(3):289-96.

Stump CS, Hamilton MT, Sowers JR. Effect of antihypertensive agents on the development of type 2 diabetes mellitus. Mayo Clin Proc. 2006;81(6):796-806.

Mukasa K. Antihypertensive drugs and insulin resistance in obesity. Internal Medicine. 2005;44(5):395-6.

Ueshiba H, Miyachi Y. Effect of long acting calcium channel blockers, amlodipine, manidipine, and clinidipine on steroid hormones and insulin resistance in hypertensive obese patients. Internal Medicine. 2004;43(7):561-5.

Reaven GM. Relationships among insulin resistance, type 2 diabetes, essential hypertension, and cardiovascular disease: similarities and differences. J Clin Hypertens (Greenwich). 2011;13(4):238-43.

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Published

2016-12-24

How to Cite

Bharati, S. M., & Singh, N. (2016). Effect of losartan and amlodipine on insulin sensitivity in non-diabetic hypertensive patients. International Journal of Basic & Clinical Pharmacology, 5(1), 202–208. https://doi.org/10.18203/2319-2003.ijbcp20160128

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Original Research Articles