Study Links Newer GLP-1 Receptor Agonists to Population-Level Improvements in HbA1c

Daniel Rotroff, MD
Credit: Cleveland Clinic

An analysis of data from more than 2.5 million patients with type 2 diabetes is shining light on the population-level impact of newer GLP-1 receptor agonists, including dulaglutide, once-weekly or oral semaglutide, and tirzepatide, on HbA1c levels.

Presented at the 84th American Diabetes Association Scientific Sessions, the analysis of insurance claims data from 2004 through 2022 indicated the advent and uptake of newer GLP-1 receptor agonists was associated with lower average HbA1c and greater proportion of patients achieving an HbA1c less than 7%.¹

Few, if any, could have imagined the role and real estate in the public consciousness of the GLP-1 receptor agonist class when the field witnessed the US Food and Drug Administration's approval of exenatide in April 2005. Since, the advent of additional GLP-1 receptor agonist medications and, more recently, dual agonists have ushered in a new era of metabolic care. Most of this can be attributed to the effects of newer GLP-1 receptor agonists, such as dulaglutide and semaglutide, which received initial approvals as adjuncts to diet and exercise for improving glycemic control in type 2 diabetes in 2014 and 2017, respectively.²

In 2022, the field saw the approval of the first dual GIP/GLP-1 receptor agonist in tirzepatide, which received approval based on data from the SURPASS program. With revelations of their benefits now extending to cardiorenal outcomes among people with type 2 diabetes, the demand for GLP-1 receptor agonists now outpaces production and has led to significant shortages.²

In the current study, a team led by Daniel Rotroff, MD, of the Cleveland Clinic, sought to evaluate the impact of newer GLP-1 receptor agonists, namely dulaglutide, oral or subcutaneous semaglutide, and tirzepatide, on HbA1c among adults with type 2 diabetes on a population level. With this in mind, the retrospective study leveraged data from the Optum Clinformatics Data Mart recorded between January 2004 and December 2022. Overall, 2,508,308 patients with type 2 diabetes met inclusion criteria for the study.¹

Investigators designed their study to use time series regressions to estimate associations between HbA1c-related outcomes and the proportion of patients on newer GLP-1 receptor agonists. For the purpose of analysis, Interrupted time series analyses were used to assess temporal trends in population-level HbA1c outcomes. Investigators noted both analyses were adjusted for potential confounders.¹

Result indicated an increasing number of patients receiving new GLP-1 receptors agonists was associated with significant decreases in population-level HbA1c at 7 to 9 months (P <.05) and significant improvement in the proportion of patients with an HbA1c of less than 7% at 2 months and at 5 to 9 months (P <.05).In the interrupted time series analysis, results suggest the introduction of newer GLP-1 receptor agonists was associated with decreased mean HbA1c and an increase in the proportion of patients with HbA1c of less than 7%.¹

“The increased adoption of newer GLP-1 receptor agonist is associated with improved average HbA1c and higher proportion of patients with HbA1c below 7% at the population level,” said study investigator Lei Lv, PhD, MPH, CPH, an evidence generation manager with Novo Nordisk, during his presentation at ADA 2024. “Top of FormBottom of FormPopulation level HbA1c control was improved after the first new GLP-1 agonist approval.”

References:

1. ^{Lei L, Wang Y, Xie L, et al. Impact of Newer GLP-1 RAs on HbA1c in U.S. Adults with Type 2 Diabetes–A Population-Level Time-Series Analysis. Presented at: American Diabetes Association (ADA) 84th Scientific Sessions. June 21 - 24, 2024. Orlando, FL.}
2. ^{Campbell P, Iapoce C. 10 years of obesity: A Decade of Advancement and challenges. HCP Live. June 23, 2023. Accessed June 23, 2024. https://www.hcplive.com/view/10-years-of-obesity-a-decade-of-advancement-and-challenges.}