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World J Diabetes. Mar 15, 2023; 14(3): 188-197
Published online Mar 15, 2023. doi: 10.4239/wjd.v14.i3.188
Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists as a promising strategy for treating diabetes
Hiroshi Nomoto
Hiroshi Nomoto, Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Hokkaido, Japan
Author contributions: Nomoto H collected the data, prepared the tables, and wrote the manuscript.
Conflict-of-interest statement: Nomoto H. has received honoraria for lectures from Novo Nordisk Pharma Ltd. and Sumitomo Pharma Co., Ltd. No funding or sponsorship was received for publication of this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hiroshi Nomoto, MD, PhD, Assistant Professor, Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Hokkaido, Japan. hnomoto@med.hokudai.ac.jp
Received: December 28, 2022
Peer-review started: December 28, 2022
First decision: January 5, 2023
Revised: January 13, 2023
Accepted: February 8, 2023
Article in press: February 8, 2023
Published online: March 15, 2023
Processing time: 77 Days and 12.5 Hours
Abstract

The maintenance of appropriate glycemic control is important for the prevention of diabetic complications in people with type 2 diabetes (T2D). Numerous oral antidiabetic drugs are now clinically available, but in particular, the introduction of injection regimens using insulin and/or glucagon-like peptide-1 receptor agonist (GLP-1RA)s represents promising step-up options for oral antidiabetic drug treatment. The recently licensed fixed-ratio combination (FRC) products, which comprise basal insulin and a GLP-1RA, have potent anti-hyperglycemic effects and reduce the undesirable side-effects of each component, such as body weight gain, hypoglycemia, and gastrointestinal symptoms. Two FRCs-insulin degludec/Liraglutide and insulin glargine/Lixisenatide-are now clinically available and, to date, several phase II/III trials have been conducted in particular groups of subjects with T2D. However, their utility in real-world clinical settings is of interest for most clinicians. Recently reported real-world clinical trials of these two FRCs in various situations have demonstrated their efficacy regarding glycemic control and the quality of life of people with T2D. Their long-term safety and efficacy require confirmation, but a treatment strategy that includes an FRC may be compatible with the concept of “well-balanced” therapy in certain groups of patients with T2D who have inadequate glycemic control.

Keywords: Clinical trial, Diabetes mellitus, type 2, Glucagon-like peptide-1 receptor, Glycemic control, Insulin, long-acting, Quality of life

Core Tip: Fixed-ratio combination injections comprising basal insulin and glucagon-like peptide-1 receptor agonists are now available, and their efficacy for glycemic control has been demonstrated in several phase II/III trials. These injections appear to be useful based on the trial data, but real-world clinical evidence regarding the use of these compounds is limited. In this review, the clinical evidence derived from phase III and real-world clinical studies regarding the glycemic control of and other outcomes in participants with type 2 diabetes is summarized.