Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Jun 28, 2021; 9(3): 297-308
Published online Jun 28, 2021. doi: 10.13105/wjma.v9.i3.297
Glycated haemoglobin reduction and fixed ratio combinations of analogue basal insulin and glucagon-like peptide-1 receptor agonists: A systematic review
Poobalan Naidoo, Celia Bouharati, Virendra Rambiritch, Sumanth Karamchand, Barbara A Tafuto, Rory F Leisegang
Poobalan Naidoo, Department of Nephrology, Inkosi Albert Luthuli Central Hospital, Durban 4092, KwaZulu-Natal, South Africa
Celia Bouharati, Department of Medical Research, Independent Researcher, Paris 75000, France
Virendra Rambiritch, Department of Pharmacology, University of KwaZulu-Natal, Durban 3629, KwaZulu-Natal, South Africa
Sumanth Karamchand, Department of Internal Medicine, Stellenbosch University and Tygerberg Hospital, Cape Town 7600, South Africa
Barbara A Tafuto, Department of Health Informatics, Rutgers University, Piscataway, NJ 08854, United States
Rory F Leisegang, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 75236, Sweden
Author contributions: Naidoo P and Tafuto BA conceived the manuscript; Leisegang RF, Rambiritch V, Karamchand S and Bouharati C reviewed all drafts and added critical comment and content; All authors read the final manuscript, consented to submission and take full responsibility for the content.
Conflict-of-interest statement: No conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Poobalan Naidoo, BPharm, MBChB, MSc, Academic Research, Doctor, Department of Nephrology, Inkosi Albert Luthuli Central Hospital, 800 Vusi Mzimela Rd, Durban 4092, KwaZulu-Natal, South Africa. poobalan1naidoo@yahoo.com
Received: March 27, 2021
Peer-review started: March 27, 2021
First decision: May 12, 2021
Revised: June 5, 2021
Accepted: July 2, 2021
Article in press: July 2, 2021
Published online: June 28, 2021
Processing time: 107 Days and 3.6 Hours
Abstract
BACKGROUND

Fixed ratio combinations (FRCs) of analogue basal insulin and glucagon-like peptide-1 receptor agonists are a newer addition to the therapeutic armamentarium for the management of type 2 diabetes mellitus. They reduce treatment complexity by combining two injectables in a single daily injectable, thus potentially improving adherence and persistence. Clinicians wanting to use FRCs would need to choose between members of the class.

AIM

To describe and contrast the glycated haemoglobin reduction of two FRCs of analogue basal insulin and glucagon like peptide-1 receptor agonist in adults with type 2 diabetes mellitus.

METHODS

The following Population, Intervention, Comparison, Outcome question was used for the primary analysis: Among adult patients with type 2 diabetes mellitus [P], what is the effect of iGlarLixi [I] compared to IDegLira [C] for bringing about glycaemic control (as measured by reduction in glycosylated haemoglobin) [O]? The Prisma Statement was used as a guideline for framing this systematic review. We searched PubMed, EMBASE and Cochrane library databases and Clinicaltrials.gov using various keywords and medical search headings related to type 2 diabetes mellitus, iGlarlixi, IDegLira and glycated haemoglobin A1c.

RESULTS

All 14 studies identified by the systematic search met the primary efficacy endpoint of reduction in glycated haemoglobin. There were no head-to-head studies between the FRCs of iGlarlixi and IDegLira, and we therefore did an indirect comparison based on a common comparator of insulin glargine U100. Both iGlarLixi and IDegLira effectively reduce glycated haemoglobin when compared to insulin glargine U100. However, using indirect comparisons, IDegLira had a greater haemoglobin A1c reducing ability (0.6% vs 0.3%). The indirect comparison is limited by the differences between the studies; the fasting blood glucose targets were slightly higher for iGlarLixi studies when compared to the IDegLira studies (4.0-5.0 mmol/L and 4.4-5.6 mmol/L), and the IDegLira study used a greater average dose of insulin glargine when compared to the iGlarLixi studies (66 U/d vs 40 U/d).

CONCLUSION

Both iGlarLixi and IDegLira effectively reduce glycated haemoglobin. Indirect comparisons, using insulin glargine as the common comparator, suggest that IDegLira reduces glycated haemoglobin to a greater extent than iGlarLixi. However, given the limitations of indirect comparisons, robust head to head studies and real-world data would better inform clinician choice and clinical practice guidelines.

Keywords: Diabetes mellitus; Fixed ratio combinations; Glycated haemoglobin, Glucagon like peptide-1 agonist; Analogue insulin

Core Tip: This systematic review investigates the effect of fixed ratio combinations of analogue insulin and glucagon like peptide-1 agonists on reduction of glycated haemoglobin. This systematic review helps fulfil a data gap that will help clinicians decide on comparative efficacy of members of the fixed ratio combination class.