Abstract

In 2017, an estimated 7.4million Americans used insulin to treat diabetes. Insulin is proven to lower A1c but can result in hypoglycemia and weight gain. Combining insulin with a glucagon-like peptide-1 receptor agonist (GLP-1-RA) may provide additional blood glucose control while limiting undesirable effects including weight gain. To characterize the clinical impact of adding a GLP-1-RA to a basal-bolus insulin regimen in patients with type 2 diabetes. This retrospective observational study used national Veteran's Health Administration data to identify patients with an existing basal-bolus insulin regimen who initiated a GLP-1-RA between January 1, 2005 and December 31, 2017. A1c, insulin total daily dose (TDD), and weight were collected at GLP-1-RA initiation (baseline), 3-, 6-, and 12-month time points and then analyzed using an intent-to-treat approach with the last observation carried forward. Decreases in A1c ≥ 0.5% and weight ≥2kg were deemed clinically significant. Among 7651 patients initiating GLP-1-RA therapy, mean A1c had a clinically significant decline at 3, 6, and 12months by -0.5%, -0.7%, and -0.7%, respectively, from a mean baseline of 9%. Patients with lower baseline A1c levels did not have clinically significant changes in A1c, whereas patients with baseline A1c ≥9% had more clinically significant declines. Insulin TDD decreased by -32, -38, and -42 units/day at 3, 6, and 12months, respectively, where the mean decrease in insulin TDD at 12months was 79 units/day among patients who discontinued bolus insulin (52.3%) compared with a mean decrease of 2 units/day among those who continued bolus insulin. Mean weight reductions at 3, 6, and 12months were -1.2, -2.3, and -2.9kg, respectively, from a mean baseline of 120.6kg. Combining a GLP-1-RA with basal-bolus insulin had a clinically significant improvement on blood glucose control, lowered insulin TDD, and reduced weight. These outcomes were achieved within 3 to 6months following GLP-1-RA initiation and were maintained through 1year.

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