Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: results of a meta-analysis

ABSTRACT

Objective: To consolidate the evidence from randomized controlled trials evaluating the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as add-on to basal insulin therapy in type 2 diabetes (T2D) patients.

Research design and methods: We searched the EMBASE® and NCBI PubMed (Medline) databases and relevant congress abstracts for randomized controlled trials evaluating the efficacy and safety of GLP-1 RAs as add-on to basal insulin compared with basal insulin with or without rapid-acting insulin (RAI) through 23 May 2016. The pooled data were analyzed using a random-effects meta-analysis model. A subanalysis was performed for trials investigating basal insulin plus GLP-1 RAs versus basal insulin plus RAI.

Results: Of the 2617 retrieved records, 19 randomized controlled trials enrolling 7,053 patients with T2D were included. Compared with basal insulin ± RAI, reduction in glycated hemoglobin (HbA1c) from baseline (difference in means: –0.48% [95% confidence interval (CI), –0.67 to –0.30]; p < 0.0001) and weight loss (–2.60 kg [95% CI, –3.32 to –1.89]; p < 0.0001) were significantly greater with basal insulin plus GLP-1 RA. The subanalysis similarly showed significant results for change in HbA1c from baseline and for weight loss, as well as a significantly lower risk of symptomatic hypoglycemia in patients treated with basal insulin plus GLP-1 RA versus basal insulin plus RAI (odds ratio, 0.52 [95% CI, 0.42 to 0.64]; p < 0.0001).

Conclusions: Addition of GLP-1 RA to basal insulin provided improved glycemic control, led to weight reduction and similar hypoglycemia rates versus an intensified insulin strategy; however, symptomatic hypoglycemia rates were significantly lower when compared with a basal insulin plus RAI.

KEYWORDS:

• GLP-1 receptor agonist
• basal insulin
• rapid-acting insulin
• type 2 diabetes
• meta-analysis

Acknowledgments

The findings of this analysis have previously been presented as a poster at 75th Scientific Sessions of the American Diabetes Association 2015 and in an oral presentation at ENDO Annual Meeting 2015.

Declaration of interest

Medical writing assistance and editorial support was provided by Rosalie Gadiot, PhD, from Excerpta Medica, and was funded by Sanofi US, Inc. CH Wysham received consulting fees from AstraZeneca, Janssen Pharmaceuticals, Eli Lilly, Boehringer Ingelheim, Novo Nordisk and Sanofi US, Inc., and received speaker honoraria from AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly USA, LLC, Janssen Pharmaceuticals, Novo Nordisk, and Sanofi US, Inc. J Lin is an employee of Novosys Health, under contract with Sanofi US, Inc. L Kuritzky received consulting fees from Boehringer Ingelheim Pharmaceuticals, Janssen Pharmaceuticals, Lilly USA, LLC, Novo Nordisk, and Sanofi US, Inc., and received speaker honoraria from Janssen Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Funding

This paper was funded by Sanofi US, Inc.