Cardiovascular outcome trials of glucose-lowering therapies

ABSTRACT

Introduction

Early initiated and long-term sustained intensive glucose control is associated with a significantly decreased risk of cardiovascular events and all-cause mortality, over and above the well-established decline in the risk of microvascular disease. Based on the recent cardiovascular outcome trial (CVOT) data, this review focuses on the various benefits of the newer medications with their positioning in the treatment algorithm and explores the place of the older medications in the management of type 2 diabetes mellitus (T2DM).

Areas covered

We searched the literature for glucose-lowering therapies for patients with T2DM. We included CVOTs conducted for newer sulphonylureas, thiazolidinediones, insulin degludec, DPP-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists.

Expert opinion

Selection of glucose-lowering therapy in the management of T2DM should be individualized and based on patient characteristics, associated comorbidities, patient preference, affordability and adherence to treatment. In view of the benefits seen in the CVOTs with SGLT2 inhibitors and GLP-1 receptor agonists, these newer classes should be the preferred choice in patients with/without established atherosclerotic cardiovascular disease and chronic kidney disease.

KEYWORDS:

• Cardiovascular outcome trials
• major adverse cardiovascular events
• type 2 diabetes
• glucose lowering therapies

Acknowledgments

We would like to acknowledge the medical writing and editorial assistance provided by consultant medical writers, Dr. Aafreen Saiyed and Dr. Suraj Ghag.

Article Highlights

• Early initiated and long-term sustained intensive glucose control is associated with a significantly decreased risk of cardiovascular events and all-cause mortality, over and above the well-established decline in the risk of microvascular disease.

• SGLT2 inhibitors or GLP-1 receptor agonists should be the drugs of choice in people with CVD; SGLT2 inhibitor should be the preferred glucose-lowering drug in the presence of heart failure or chronic kidney disease.

• These drug classes safely reduce glycated hemoglobin with few or no hypoglycemic episodes, particularly if not combined with insulin or sulphonylureas.

• Macrovascular events such as myocardial infarction and stroke, risk of hospitalization due to heart failure or unstable angina pectoris, and progression of renal disease are consistently lowered with SGLT2 inhibitors, across a broad spectrum of people with T2DM.

• The long-acting GLP-1 receptor agonists, viz. liraglutide, exenatide long-acting release, albiglutide, and semaglutide, demonstrated consistent reduction in 3-point MACE.

Declaration of interest

KK has acted as a consultant and speaker for AstraZeneca, Berlin-Chemie AG/Menarini Group, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, NAPP, Merck Sharp & Dohme, Janssen, and Boehringer Ingelheim, has received grants in support of investigator and investigator-initiated trials from AstraZeneca, Janssen, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Merck Sharp & Dohme. MJD reports personal fees from Novo Nordisk, Sanofi-Aventis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Mitsubishi Tanabe Pharma Corporation, and Takeda Pharmaceuticals International and grants from Novo Nordisk, Sanofi-Aventis, Eli Lilly, Boehringer Ingelheim, and Janssen. SS reports personal fees from Amgen, personal fees from AstraZeneca, personal fees from NAPP, personal fees from Lilly, personal fees from Merck Sharp & Dohme, personal fees from Novartis, personal fees from Novo Nordisk, personal fees from Roche, personal fees from Sanofi-Aventis, personal fees from Boehringer Ingelheim, grants from AstraZeneca, grants from Sanofi-Aventis, grants from Servier, grants from Janssen, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

MJD, SS, and KK acknowledge the National Institute for Health Research (NIHR) – Applied Research Collaborations (ARC) East Midlands and the NIHR Leicester Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.