Rationale for, Initiation and Titration of the Basal Insulin/GLP-1RA Fixed-Ratio Combination Products, IDegLira and IGlarLixi, for the Management of Type 2 Diabetes.

Virginia Valentine,Jennifer Goldman,Jay H. Shubrook

doi:10.1007/s13300-017-0287-y

Abstract

Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response. Native glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the gut in response to nutrient ingestion; it increases insulin secretion, inhibits glucagon secretion, and prolongs gastric emptying, thereby lowering overall food intake. As its glucose-lowering action is glucose dependent, a GLP-1 receptor agonist (GLP-1RA) achieves these benefits with a lower risk of hypoglycemia compared with other diabetes therapies. Two products, an insulin degludec/liraglutide combination (IDegLira) and an insulin glargine/lixisenatide combination (IGlarLixi), were approved for use in adults with T2D by the US Food and Drug Administration in 2016. The efficacy and safety of these two basal insulin/GLP-1RA combination products were studied in the DUAL program (NCTs 01336023, 01392573, 01676116, 01618162, 01952145, and 02298192) and the LixiLan program (NCTs 02058160 and 02058147). Compared with basal insulin, insulin/GLP-1RA fixed-ratio combinations are superior at reducing HbA1c with weight neutrality or weight loss rather than weight gain, as well as reduced hypoglycemia rates, and reduced insulin-dose requirement with IDegLira. A combination of different medications may often be required to achieve glycemic control, and fixed-ratio combination products allow such therapies to be given in simple regimens. Clinical trial data for these products highlight the great potential of these agents, not merely their efficacy and safety but also their ease of use and decreased injection burden for patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0287-y) contains supplementary material, which is available to authorized users.

Highlights

Type 2 diabetes (T2D) is a progressive multiorgan disease [1,2,3] that accounts for approximately 90% of all cases of diabetes; it is a major cause of morbidity and mortality in both high-income and developing countries [4, 5]
Insulin/GLP-1 receptor agonist (GLP-1RA) fixed-ratio combinations are superior at reducing HbA1c with weight neutrality or weight loss rather than weight gain, as well as reduced hypoglycemia rates, and reduced insulin-dose requirement with IDegLira
Data aligned to number of decimal places across each individual row ANCOVA analysis of covariance, BID twice daily, EOT end of trial, FAS full analysis set, FPG fasting plasma glucose, GLP-1RA glucagon-like peptide-1 receptor agonist, IDegLira insulin degludec/liraglutide combination, IGlar U100 insulin glargine 100 units/mL, LOCF last observation carried forward, Met metformin, MMRM mixed model for repeated measurement, N/A not available, oral antidiabetic drugs (OADs) oral antidiabetic drug, OD once daily, PG plasma glucose, pio pioglitazone, PYE patient-year of exposure, SAS safety analysis set, SD standard deviation, SMPG self-measured plasma glucose, SU sulfonylurea, U units, 1WT

Summary

Introduction

Type 2 diabetes (T2D) is a progressive multiorgan disease [1,2,3] that accounts for approximately 90% of all cases of diabetes; it is a major cause of morbidity and mortality in both high-income and developing countries [4, 5].

Results

Conclusion