Clinical Impact of GLP-1 receptor agonists in veterans receiving basal-bolus insulin

In 2017, an estimated 7.4 million 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 ≥2 kg were deemed clinically significant.

Among 7651 patients initiating GLP-1-RA therapy, mean A1c had a clinically significant decline at 3, 6, and 12 months 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 12 months, respectively, where the mean decrease in insulin TDD at 12 months 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 12 months were -1.2, -2.3, and -2.9 kg, respectively, from a mean baseline of 120.6 kg.

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 6 months following GLP-1-RA initiation and were maintained through 1 year.