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

Pharmacotherapy. 2022 Jan;42(1):45-52. doi: 10.1002/phar.2648. Epub 2021 Dec 3.

Abstract

Background: 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.

Objective: To characterize the clinical impact of adding a GLP-1-RA to a basal-bolus insulin regimen in patients with type 2 diabetes.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: glucagon-like peptide-1 receptor agonist; glycosylated hemoglobin A1c; insulin; type 2 diabetes; weight loss.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug Therapy, Combination
  • Glucagon-Like Peptide-1 Receptor* / antagonists & inhibitors
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Insulin* / administration & dosage
  • Retrospective Studies
  • Treatment Outcome
  • Veterans

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin