Differential Metabolic Effects of Beta-Blockers: an Updated Systematic Review of Nebivolol
- 648 Downloads
Blood pressure management in hypertensive patients with metabolic abnormalities is challenging, since many of the antihypertensive drugs adversely affect metabolism. Besides effective control of blood pressure in patients with hypertension, third-generation beta-blockers such as nebivolol offer additional benefits for central hemodynamics and neutral or beneficial effects on metabolism. Emerging clinical data suggest that nebivolol also has similar effects on metabolism in obese hypertensive and hypertensive diabetic patients. The present article will provide a systematic analysis of the pathophysiological links among hypertension, insulin resistance, and metabolic syndrome. We will also summarize the available clinical evidence regarding the metabolic effects of beta-blockers in hypertensive patients, with an emphasis on nebivolol. Nebivolol exerts neutral or beneficial effects on insulin sensitivity and lipid metabolism in hypertensive patients, owing to its nitric oxide-mediated vasodilatory and antioxidative properties. Thus, nebivolol could be a favorable therapeutic option for the treatment of hypertension in patients with impaired glucose and lipid metabolism.
KeywordsHypertension Insulin sensitivity Lipid metabolism Nebivolol Obesity
Editorial support for the preparation of this manuscript was provided by the SPRIM Company, Singapore, through an unrestricted educational grant by A. Menarini.
Compliance with Ethical Standards
Conflict of Interest
Drs. Marketou, Gupta, and Vardas declare no conflicts of interest relevant to this manuscript. Dr. Jain reports grants from A. Manarini, Singapore, and support from SPRIM Asia Pacific Ltd, Singapore.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 8.Rizos E, Bairaktari E, Kostoula A, Hasiotis G, Achimastos A, Ganotakis E, et al. The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared to that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study. J Cardiovasc Pharmacol Ther. 2003;8:127–34.CrossRefPubMedGoogle Scholar
- 9.•• Celik T, Iyisoy A, Kursaklioglu H, Kardesoglu E, Kilic S, Turhan H, et al. Comparative effects of nebivolol and metoprolol on oxidative stress, insulin resistance, plasma adiponectin and soluble P-selectin levels in hypertensive patients. J Hypertens. 2006;24:591–6. A prospective, blinded, randomized study highlighting that nebivolol, in contrast to metoprolol, improved oxidative stress, insulin sensitivity, decreased plasma soluble P-selectin and increased adiponectin levels in hypertensive patients.CrossRefPubMedGoogle Scholar
- 20.NCEP. National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106:3143–421.Google Scholar
- 31.Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil–Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003;290:2805–16.CrossRefPubMedGoogle Scholar
- 45.Higgins M, Kannel W, Garrison R, Pinsky J, Stokes J. Hazards of obesity—the Framingham experience. Acta Med Scand Suppl. 1998;723:23–36.Google Scholar
- 49.Weidmann P, Ferrier C, Saxenhofer H, Uehlinger DE, Trost BN. Serum lipoproteins during treatment with antihypertensive drugs. Drugs. 1998;35 Suppl 6:118–34.Google Scholar
- 53.Hauf-Zachariou U, Widmann L, Zülsdorf B, Hennig M, Lang PD. A double-blind comparison of the effects of carvedilol and captopril on serum lipid concentrations in patients with mild to moderate essential hypertension and dyslipidaemia. Eur J Clin Pharmacol. 1993;45:95–100.CrossRefPubMedGoogle Scholar
- 56.• Marazzi G, Volterrani M, Caminiti G, Iaia L, Cacciotti L, Massaro R, et al. Effectiveness of nebivolol and hydrochlorothiazide association on blood pressure, glucose, and lipid metabolism in hypertensive patients. Adv Ther. 2010;27:655–64. This study indicates that the addition of hydrochlorothiazide on nebivolol treatment optimizes blood pressure control in a high number of patients resistant to monotherapy without a negative impact on patients’ glucose and lipid profile.CrossRefPubMedGoogle Scholar
- 60.Kiso T, Namikawa T, Tokunaga T, Sawada K, Kakita T, Shogaki T, et al. Anti-obesity and anti-diabetic activities of a new beta3 adrenergic receptor agonist, (S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-propenyl] phenoxy] acetic acid ethanedioic acid (SWR-0342SA), in KK-Ay mice. Biol Pharm Bull. 1999;22:1073–8.CrossRefPubMedGoogle Scholar
- 64.• Van Bortel LM. Efficacy, tolerability and safety of nebivolol in patients with hypertension and diabetes: a post-marketing surveillance study. Eur Rev Med Pharmacol Sci. 2010;14:749–58. A surveillance study showing that nebivolol treatment is associated with a significantly reduced BP, improved blood glucose and LDL cholesterol levels and is well tolerated in hypertensive patients with concomitant diabetes.PubMedGoogle Scholar
- 67.• Deedwania P, Shea J, Chen W, Brener L. Effects of add-on nebivolol on blood pressure and glucose parameters in hypertensive patients with prediabetes. J Clin Hypertens (Greenwich). 2013;15:270–8. A multicenter trial showing that nebivolol, added to an ACE inhibitor or ARB, provides additional blood pressure reduction with little or no effect on glucose metabolism in hypertensive patients with prediabetes.CrossRefGoogle Scholar
- 68.•• Ozyıldız AG, Eroglu S, Bal U, Atar I, Okyay K, Muderrisoglu H. Effects of carvedilol compared to nebivolol on insulin resistance and lipid profile in patients with essential hypertension. J Cardiovasc Pharmacol Ther. 2016. A prospective, randomized study indicating the favourable effects of new generation b-blockers on glucose, insulin, insulin resistance, and the lipid profile.Google Scholar
- 69.•• Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Hypertension. 2012;59:893–8. A comparative study indicating that treatment with metoprolol decreased insulin sensitivity and increased oxidative stress and the antifibrinolytic plasminogen activator inhibitor 1 in patients with metabolic syndrome, whereas nebivolol lacked detrimental metabolic effects.CrossRefPubMedPubMedCentralGoogle Scholar
- 70.••Ladage D, Reidenbach C, Rieckeheer E, Graf C, Schwinger RH, Brixius K. Nebivolol lowers blood pressure and increases weight loss in patients with hypertension and diabetes in regard to age. J Cardiovasc Pharmacol. 2010;56:275–81. A large study in five thousand thirty-one male and female patients indicating that nebivolol is effective in treating patients with diabetes suffering from high blood pressure and metabolic syndrome.CrossRefPubMedGoogle Scholar
- 72.Predel HG, Mainka W, Schillings W, Knigge H, Montiel J, Fallois J, et al. Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension. J Hum Hypertens. 2001;15:715–21.CrossRefPubMedGoogle Scholar
- 82.• Bhosale VV, Inamdar SC, Karande VB, Burute SR, Murthy MB, Ghatak A. Beneficial effects of nebivolol in comparison with atenolol on safety and tolerability in essential hypertension. J Clin Diagn Res. 2014;8:HC01–4. A prospective, double blind, comparative controlled clinical study highlighting the superior efficacy and safety of nebivolol compared to atenolol.PubMedPubMedCentralGoogle Scholar