Effects of β-blockers on glucose and lipid metabolism

Abstract

Background:

Activation of the sympathetic nervous system (SNS) has been linked to hypertension. Beta-blockers, which decrease SNS activation via β-adrenergic receptor antagonism, are effective in lowering blood pressure and reducing cardiovascular morbidity and mortality in several conditions, including post-myocardial infarction and heart failure. Despite these clinical benefits, many physicians are reluctant to prescribe β-blockers because of perceived negative metabolic effects, including reduced glycemic control, masking of hypoglycemia, insulin resistance, and dyslipidemia.

Objective:

This article reviews the pathophysiology of hypertension and either insulin resistance or dyslipidemia as well as treatment effects from glucose- and lipid-lowering regimens on cardiovascular morbidity and mortality. Based on a PubMed literature search from January 1980 to December 2008, the effects of nonvasodilating (atenolol, metoprolol, and propranolol) and vasodilating β-blockers (carvedilol, labetalol, and nebivolol) on parameters of glucose and lipid metabolism in hypertension are presented. Preference for clinical trial inclusion was given to randomized, controlled trials with at least 100 patients. Limitations of a drug class literature review may include trial inclusion bias with associated result skewing and underrepresentation of an individual agent, which may give different results.

Results:

Beta-blockers differ in terms of their mechanism of action and their effects on glucose and lipid metabolism. Nonvasodilating β-blockers reduce blood pressure in association with a cardiac output reduction and may increase or have no appreciable effect on peripheral vascular resistance. As a result, nonvasodilating β-blockers are associated with a worsening of glycemic and lipidic control. In contrast, vasodilating β-blockers reduce peripheral vascular resistance but have little or no effect on cardiac output. Numerous studies have established that vasodilating β-blockers are associated with more favorable effects on glucose and lipid profiles than nonvasodilating β-blockers.

Conclusions:

Improvements in glucose and lipid metabolism mediated by vasodilating β-blockers may help reduce coronary artery disease risk among high-risk patients with hypertension.

Key words::

• Adrenergic
• Beta-blockers
• Diabetes mellitus
• Dyslipidemias
• Hypertension

Transparency

Declaration of funding

Support from GlaxoSmithKline was limited to editorial services provided by a medical writer (see below). The author controlled the development of this review manuscript since its inception, including the concept and design, drafting and reviewing/editing and final approval of the manuscript, and takes full responsibility for it and the views expressed. The author has not received any financial support for this work and has had no contact with any GSK personnel on this manuscript. Whilst GSK manufactures a proprietary form of one of the agents discussed in the review, it is of note that carvedilol is now a generic medication.

Declaration of financial/other relationships

V.A.F. has disclosed receiving honoraria for consulting and lectures from GlaxoSmithKline, Novartis, Takeda, Novo Nordisk, Sanofi-Aventis, Eli Lilly and Daiichi Sankyo. His institution, Tulane University, has received research support from GlaxoSmithKline, Novartis, Novo Nordisk, Takeda, AstraZeneca, Pfizer, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, National Institutes of Health, and American Diabetes Association.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewers 1 and 2 have disclosed that they have no relevant financial relationships.

Acknowledgments

The author thanks Ann Marie Fitzmaurice, PhD, ProEd Communications, Inc. (Beachwood, Ohio, USA), for her medical editorial assistance, which was supported by GlaxoSmithKline, Philadelphia, PA.