Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2018; 9(12): 230-238
Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.230
Effects of glucose-lowering agents on cardiorespiratory fitness
Hidetaka Hamasaki
Hidetaka Hamasaki, Endocrinology and Metabolism, Internal Medicine, Hamasaki Clinic, Kagoshima 890-0046, Japan
Author contributions: Hamasaki H wrote the review.
Conflict-of-interest statement: No conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author to: Hidetaka Hamasaki, MD, PhD, Doctor, Endocrinology and Metabolism, Internal Medicine, Hamasaki Clinic, 2-21-4 Nishida, Kagoshima 890-0046, Japan.
Telephone: +81-99-2503535 Fax: +81-99-2501470
Received: August 27, 2018
Peer-review started: August 27, 2018
First decision: October 5, 2018
Revised: October 15, 2018
Accepted: November 26, 2018
Article in press: November 27, 2018
Published online: December 15, 2018

Exercise therapy is essential for the management of type 2 diabetes (T2D). However, patients with T2D show lower physical activity and reduced cardiorespiratory fitness than healthy individuals. It would be ideal for clinicians to co-prescribe glucose-lowering agents that improve cardiorespiratory fitness or exercise capacity in conjunction with exercise therapy. Metformin does not improve cardiorespiratory fitness and may attenuate any beneficial effect of exercise in patients with T2D. In contrast, thiazolidinediones appear to improve cardiorespiratory fitness in patients with T2D. Although evidence is limited, sodium–glucose cotransporter 2 (SGLT2) inhibitors may improve cardiorespiratory fitness in patients with heart failure, and the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on cardiorespiratory fitness is controversial. Recent clinical trials have shown that both SGLT2 inhibitors and GLP-1 receptor agonists exert a favorable effect on cardiovascular disease. It becomes more important to choose drugs that have beneficial effects on the cardiovascular system beyond glucose-lowering effects. Further studies are warranted to determine an ideal glucose-lowering agent combined with exercise therapy for the treatment of T2D.

Keywords: Type 2 diabetes, Glucagon-like peptide l receptor agonist, Cardiorespiratory fitness, Exercise capacity, Metformin, Thiazolidinedione, Sodium-glucose cotransporter 2 inhibitors

Core tip: What is the most effective combination of drugs and exercise for the treatment of type 2 diabetes? It has become increasingly important for clinicians to prescribe drugs that reduce cardiovascular disease and mortality in addition to their glucose-lowering effects. This review summarized the current literature investigating the effect of glucose-lowering agents on cardiorespiratory fitness. Thiazolidinediones, sodium–glucose cotransporter 2 inhibitors, and glucagon-like peptide-l receptor agonists have the potential to improve cardiorespiratory fitness; however, further research will be needed to confirm.