Blood Pressure-lowering Effect of Newer Antihyperglycemic Agents

(SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors)

Charalampos I. Liakos; Dimitrios P. Papadopoulos; Elias A. Sanidas; Maria I. Markou; Erifili E. Hatziagelaki; Charalampos A. Grassos; Maria L. Velliou; John D. Barbetseas

Disclosures

Am J Cardiovasc Drugs. 2021;21(2):123-137. 

In This Article

Abstract and Introduction

Abstract

The prevalence of arterial hypertension is high in patients with diabetes mellitus (DM). When DM and hypertension coexist, they constitute a dual cardiovascular threat and should be adequately controlled. Novel antihyperglycemic agents, including sodium-glucose co-transporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been used in the treatment of DM. Beyond their glucose-lowering effects, these drugs have shown beneficial pleiotropic cardiovascular effects, including lowering of arterial blood pressure (BP), as acknowledged in the 2019 European Society of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes, and cardiovascular diseases. The purpose of this review was to summarize the available information on the BP-reducing effects of these new glucose-lowering drug classes and provide a brief report on underlying pathophysiological mechanisms. We also compare the three drug classes (SGLT-2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors) in terms of their BP-lowering effect and show that the greater BP reduction seems to be achieved with SGLT-2 inhibitors, whereas DPP-4 inhibitors have probably the mildest antihypertensive effect.

Introduction

Diabetes mellitus (DM) and arterial hypertension frequently coexist, so the prevalence of hypertension in patients with DM is high, reaching ≈ 50% at the time of type 2 DM (T2DM) diagnosis and increasing with the longer duration of DM.[1,2] Coexistence of DM and hypertension, especially if blood pressure (BP) is not well-controlled, substantially increases cardiovascular morbidity and mortality.[2] Optimal BP control is essential for the management of patients with DM because it is one of the most effective ways to prevent vascular complications and death.[2]

New antihyperglycemic agents have been approved and used in clinical practice over the last 15 years for the management of DM. They include sodium-glucose co-transporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors. These glucose-lowering agents have recently shown beneficial cardiovascular effects, even in patients without DM.[3] Their pleiotropic effects include lowering of arterial BP. The BP-lowering effects of these drugs were acknowledged in the 2019 European Society of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes, and cardiovascular diseases[2] and must be considered when managing DM and BP.[2]

The present review presents the degree of antihypertensive action of these novel antihyperglycemic drugs according to the latest clinical trial data from their use in patients with T2DM. Possible underlying pathophysiological mechanisms are briefly reported. Moreover, we compare the three glucose-lowering classes (SGLT-2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors) in terms of their BP-lowering effect. We discuss large-scale cardiovascular outcomes trials, smaller randomized controlled BP outcomes studies, and available meta-analyses published over the last 15 years. For better uniformity and comparability of the results, we preferred to discuss placebo-controlled trials where available.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....