Basal insulin treatment optimization in T2DM: GLP-1 Receptor Agonists in loose addition or in fixed dose combination

Abstract

Administration of basal insulin formulations is often used when oral therapies fail to achieve and/or maintain adequate glucose control in T2DM. However, observational studies documented that a large percentage of basal insulin treated subjects fails to achieve glycemic targets. Among the possible strategies to intensify basal insulin therapy, addition of a GLP-1 RA has several advantages. Indeed GLP-1 RA mechanism of action could be seen as complementary to insulin action. Furthermore, studies have shown that addition of a GLP-1 RA to basal insulin improves HbA1c with a minimal increase in the risk of hypoglycemia and null or modest weight gain. Addition of a GLP-1 RA to basal insulin therapy might be easier if performed by switching from daily basal insulin injections to daily injections of a fixed dose combination of a GLP-1 RA+basal insulin preparation. Two such fixed combinations are presently available, IDegLira (Degludec Insulin + Liraglutide) and IGlarLixi (Insulin Glargine+Lixisenatide). Two studies with IDegLira and one study with IGlarLixi have shown that these combinations are more efficacious and safer than mere up-titration of basal insulin. Use of fixed dose GLP-1 RA+basal insulin combination appears therefore an excellent strategy of basal insulin intensification. No studies are availbe directly comparing efficacy and safety of IGlarLixi and IDegLira. Data obtained in registration trials appear numerically better for IDegLira. Furthermore, as compared to IGlarLixi, IDegLira offers a greater flexibility in time of administration. KEY WORDS basal insulin; GLP-1 RA; liraglutide; lixisenatide; fixed dose combination.