Use of GLP-1 agonists, such as semaglutide, surged among US adults with type 2 diabetes in recent years, through March 2022, and dethroned DPP-4 inhibitors as the top incretin-based drug class, according to a retrospective review of insurance-claims data from more than 1 million individuals.
By January-March 2022, 56.6% of US adults with type 2 diabetes prescribed an incretin-based treatment were taking a glucagon-like peptide-1 (GLP-1) agonist and 38.7% were taking a dipeptidyl peptidase-4 (DPP-4) inhibitor, Elisabetta Patorno, MD, and colleagues report in an abstract released in advance from the European Association for the Study of Diabetes (EASD) 2023 annual meeting, to be held on October 2-6, 2023 in Hamburg, Germany.
These usage rates sharply diverged from the earliest period the researchers examined — 4 years earlier in January-March 2018 — when DPP-4 inhibitors were used by 62.4% of adults with type 2 diabetes on any incretin-based regimen and 37.6% were taking a GLP-1 agonist.
This shift was largely driven by accumulating evidence for clinically meaningful weight loss with GLP-1 agonists, especially semaglutide when used for people with type 2 diabetes as Ozempic (Novo Nordisk) or for treating people with obesity as Wegovy (Novo Nordisk).
Market Share of GLP-1 Agonists ‘Likely to Expand‘ Further
“The importance of the DPP-4 inhibitor class will further decrease when effective alternatives such as GLP-1 agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors can be used,” said Alexander Kutz, MD, a co-author of the report, in a statement released by EASD.
“The market share of GLP-1 agonists is likely to expand in patients with type 2 diabetes,” especially those who also have obesity, said Kutz, who like Patorno is a pharmacoepidemiologist at Brigham and Women’s Hospital in Boston, Massachusetts.
Incretin-based agents currently account for roughly a third of all medications prescribed to people with type 2 diabetes, the authors say. GLP-1 is an incretin hormone, and receptor agonists mimic its action. The DPP-4 enzyme inactivates incretin hormones, and so inhibiting the enzyme boosts incretin activity.
The obesity-driven shift in positioning of agents for people with type 2 diabetes will likely extend to tirzepatide (Mounjaro), which acts as both a GLP-1 agonist and has agonist activity on the receptor for another incretin, glucose-dependent insulinotropic polypeptide (GIP). The US Food and Drug Administration approved tirzepatide for type 2 diabetes in May 2022, too late for inclusion in the data the researchers reviewed. Plus, tirzepatide prescribing may lag for a few years as clinicians gain experience, and some might await results from the cardiovascular outcomes trial SURPASS-CVOT , said Kutz. SURPASS-CVOT has enrolled more than 13,000 adults with type 2 diabetes and is currently scheduled to finish by October 2024.
Injected Semaglutide Had the Biggest Gain
The study by Patorno and colleagues included 1,065,592 US adults with type 2 diabetes taking an incretin-based medication in the Clinformatics Data Mart database maintained by Optum on claims it processed on behalf of various US commercial insurers, including insurers that service certain Medicare beneficiaries.
The claims data had granularity for specific agents in the GLP-1 agonist class. Injected semaglutide, given once-weekly, spiked from no use early in 2018 to a third of GLP-1 agonist use by the start of 2022.
However, use of liraglutide (Victoza, Novo Nordisk), a daily subcutaneous injection, dropped from a 44.2% share in early 2018 to 10.0% in early 2022. Dulaglutide (Trulicity, Lilly), a weekly injection, showed a small increase, from a 35.2% share in 2018 to 42.1% in 2022, and oral semaglutide (Rybelsus, Novo Nordisk) jumped from no use in 2018 to a 7.7% share in 2022. Among the DPP4 inhibitors, sitagliptin (Januvia, Merck) was most commonly used, followed by linagliptin (Tradjenta, Boehringer Ingelheim) and saxagliptin (Onglyza, AstraZeneca). Use of all three DPP-4 inhibitors fell from 2018 to 2022.
Additional analyses showed that compared with people starting a DPP-4 inhibitor during the period examined, those who started a GLP-1 agonist were 54%-64% more likely to have obesity and 18%-46% more likely to receive care from an endocrinologist. Those starting a GLP-1 agonist were also significantly less likely to have chronic kidney disease or dementia.
Although Kutz and Patorno foresee continued increases in the use of agents that act as GLP-1 agonists in US adults with type 2 diabetes, they also stress the ongoing role for sitagliptin and other DPP-4 inhibitors.
This class “may still be preferred in older and multimorbid patients at higher risk for frailty,” such as patients who live in nursing homes, they said in the EASD statement.
The study received no commercial funding. Patorno has reported no relevant financial relationships. Kutz has reported receiving an educational grant from Novo Nordisk, the company that markets semaglutide (Ozempic) and liraglutide (Victoza).
EASD Annual Meeting 2023. Abstract #667. Released on July 27, 2023.
Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler
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