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Review
. 2021 Jul;23(7):1445-1452.
doi: 10.1111/dom.14365. Epub 2021 Mar 31.

Titratable fixed-ratio combination of basal insulin plus a glucagon-like peptide-1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes

Fernando Gomez-Peralta  1 , Ebaa Al-Ozairi  2 , Edward B Jude  3   4 , Xiaoying Li  5 , Julio Rosenstock  6
Affiliations
Review

Titratable fixed-ratio combination of basal insulin plus a glucagon-like peptide-1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes

Fernando Gomez-Peralta et al. Diabetes Obes Metab. 2021 Jul.

Abstract

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c _targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon-like peptide-1 receptor agonist (GLP-1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real-world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta-analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head-to-head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP-1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP-1 RAs as an alternative treatment option.

Keywords: GLP-1 analogue; basal insulin; glycaemic control; insulin therapy; type 2 diabetes.

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Conflict of interest statement

FG‐P has acted as an advisor for Abbott Diabetes, AstraZeneca, Novartis, Novo Nordisk and Sanofi; has been an investigator in clinical trials for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi; and has acted as a speaker for Abbott Diabetes, AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly, Novartis, Novo Nordisk and Sanofi. EA‐O has no conflicts of interest to declare. EBJ has received advisory board honoraria and grant/research support from Sanofi and has received speaker honoraria from Bayer AG, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Takeda. XL has no conflicts of interest to declare. JR has been a consultant for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen, Novo Nordisk, Oramed and Sanofi, and has received grant/research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, GlaxoSmithKline, Intarcia, Janssen, Lexicon, Merck, Novartis, Novo Nordisk, Oramed, Pfizer and Sanofi.

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