Real-world glycemic control from GLP-1RA therapy with and without concurrent insulin in patients with type 2 diabetes

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy in patients with uncontrolled type 2 diabetes (T2D), with no specific guidance as to timing versus insulin. Furthermore, real-world data assessing GLP-1RA outcomes with or without concurrent insulin therapy are lacking. OBJECTIVE: To identify glycemic response with GLP-1RAs by insulin use in patients with T2D at 1-year follow-up to inform decisions regarding GLP- 1RA use with or without insulin. METHODS: This uncontrolled retrospective cohort study included adults with T2D in the Quintiles Electronic Medical Records Database who were newly prescribed GLP-1RA therapy with exenatide once weekly or liraglutide once daily between February 1, 2012, and March 31, 2013 (index period). Primary outcomes were change in hemoglobin A1c (A1c) at 1 year and attainment of A1c < 7%, < 8%, and < 9%. Results were stratified by baseline insulin use, which was defined as no insulin use at baseline, insulin initiated with a GLP-1RA on index date, and insulin prescribed before starting GLP-1RA therapy. Secondary outcomes included 1-year weight, lowdensity lipoprotein cholesterol (LDL-C), and blood pressure outcomes for the study population. Adjusted mean (marginal) change in A1c at 1 year was estimated using multivariate linear regression, and multivariate logistic regression was used to estimate the likelihood of patients attaining A1c < 7% at follow-up, controlling for potential confounders. RESULTS: This study included 5,141 patients with a mean (SD) age of 57.0 (10.9) years, 53.5% of whom were females, and with a mean baseline A1c of 8.4% (1.6). Overall, 35.4% had no baseline insulin use, 42.9% were prescribed insulin before starting GLP-1RA therapy, and 21.7% were started on insulin with a GLP-1RA. The adjusted mean A1c reduction at 1 year was 0.75% (95% CI = -0.86 to -0.63) for patients initiating insulin on index date, 0.61% (95% CI = -0.70 to -0.51) for patients with no baseline insulin use, and 0.23% (95% CI = -0.33 to -0.13) for patients prescribed insulin before GLP-1RA therapy. Patients with no baseline insulin or who coinitiated insulin and a GLP-1RA were more likely to attain A1c < 7% at follow-up versus patients prescribed insulin before initiating GLP-1RA therapy (OR = 1.50, 95% CI = 1.08 to 2.09 and OR = 1.85, 95% CI = 1.30 to 2.62, respectively). At 1-year follow-up, significant improvements in weight, LDL-C, and blood pressures were also observed. CONCLUSIONS: GLP-1RA therapy was associated with significant improvements in glycemic control when used with or without insulin, as well as reductions in weight and LDL-C overall. However, greater A1c reductions and a higher likelihood of attaining A1c goal levels were observed when a GLP-1RA was initiated alone or with insulin than when a GLP-1RA was added to a regimen that included insulin. GLP-1RA therapy is an effective treatment option when used with or without insulin and may be considered in patients with uncontrolled glycemia.