An indirect treatment comparison of the efficacy of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) in patients with type 2 diabetes uncontrolled on basal insulin

Abstract

Aims: To obtain estimates of the relative treatment effects between insulin degludec/liraglutide (IDegLira) and insulin glargine U100/lixisenatide (iGlarLixi) in patients with type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin therapy.

Materials and methods: Data from phase 3 trials providing evidence for estimating the relative efficacy and safety of IDegLira vs iGlarLixi in patients uncontrolled on basal insulin-only regimens were used in this analysis. Outcomes of interest were changes in HbA_1c, body weight and insulin dose, and rate ratio of hypoglycemia. The indirect comparison of the reported trial findings followed the principles of Bucher et al.

Results: IDegLira was estimated to provide a 0.44 [95% CI = 0.17–0.71] %-point reduction in HbA_1c compared with iGlarLixi. Body weight was reduced by 1.42 [95% CI = 0.35–2.50] kg with IDegLira compared with iGlarLixi. Insulin dose was comparable between the two interventions. The rate of severe or blood glucose-confirmed (self-measured plasma glucose [SMPG] ≤ 3.1 mmol/L) hypoglycemia with IDegLira was approximately half that of iGlarLixi (rate ratio = 0.51 [95% CI = 0.29–0.90]). However, using the American Diabetes Association definition of documented symptomatic hypoglycemia (SMPG ≤3.9 mmol/L) the rate was comparable between the two treatments (rate ratio = 1.07 [95% CI = 0.90–1.28]).

Limitations: The assumptions made in the indirect comparison and differences between the included trials in baseline HbA_1c levels, previous use of sulfonylureas, definitions of hypoglycemia, presence or absence of run-in period, the different duration of the trials, and the cross-over design of one of the trials.

Conclusions: The results of this indirect treatment comparison demonstrate that, among patients with T2DM uncontrolled on basal insulin, treatment with IDegLira results in a greater reduction of HbA_1c and a greater reduction in body weight compared with iGlarLixi at similar insulin doses.

Keywords:

• GLP-1
• basal insulin
• glycemic control network meta-analysis
• liraglutide
• insulin analogs

Transparency

Declaration of funding

Sponsorship for this study and article publication fees were funded by Novo Nordisk A/S, Søborg, Copenhagen, Denmark. Precision Health Economics received funding from Novo Nordisk to perform the analysis in this study.

Declaration of financial/other interests

ME has received honoraria and research awards from Novo Nordisk, Sanofi Aventis, MSD, and Novartis. LKB has participated in advisory panels and is on the speakers’ bureau for Novo Nordisk. JHB, US, and AA are employees of Novo Nordisk A/S. TJA was an employee of Novo Nordisk A/S during the time of the analysis and review of the manuscript. JPJ is an employee of Precision Health Economics. Peer reviewers on this manuscript have received an honorarium from JME for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

Writing, editing, and submission assistance in the preparation of this manuscript was provided by Paul Tisdale and Beverly La Ferla of Watermeadow Medical, an Ashfield company, part of UDG Healthcare plc. Support for this assistance was funded by Novo Nordisk.