TOPLINE:

Compared with DPP-4 inhibitor therapy, sustained GLP-1 receptor agonist (GLP-1 RA) therapy was associated with greater short‑ and long‑term improvements in A1c levels and a modest reduction in the risk for all-cause mortality in patients with type 2 diabetes (T2D).

METHODOLOGY:

• Researchers in Denmark emulated a target trial using real-world data to examine whether the sustained use of GLP-1 RAs vs DPP-4 inhibitors improves A1c levels and affects all-cause mortality in patients with T2D.
• They analysed data of 50,815 adults with T2D who were new users of those drug classes: 16,619 started a GLP‑1 RA (median age, 58 years; 58.9% men) and 34,196 started a DPP‑4 inhibitor (median age, 63 years; 63.3% men); none had insulin or SGLT2 inhibitor use in the prior 6 months.
• Sustained exposure was defined as redeeming at least one prescription for the assigned drug class in every 6-month interval, with no redeemed prescriptions for the comparator class in those intervals.
• The primary outcome was the absolute probability of achieving improvement in at least one A1c category within 1 year under sustained treatment with either GLP-1 RAs or DPP-4 inhibitors (A1c categories: < 42, ≥ 42-48, ≥ 48-53, ≥ 53-64, and > 64 mmol/mol).
• This probability was also estimated every 6 months up to 4.5 years.

TAKEAWAY:

• At 1 year, the probability of improving by at least one A1c category was 82.7% with sustained GLP-1 RAs vs 67.1% with sustained DPP-4 inhibitors, with an absolute difference of 15.7% (95% CI, 14.8%-16.5%).
• GLP‑1 RAs consistently demonstrated an advantage over DPP‑4 inhibitors, with absolute risk differences of 12.0% at 2 years, 9.6% at 3 years, and 8.2% at 4 years.
• Sustained GLP-1 RA therapy was linked to a modest reduction in the risk for all-cause mortality compared with DPP-4 inhibitor therapy.
• At 1 year, patients using GLP-1 RAs were more likely than those using DPP-4 inhibitors to achieve meaningful reductions in A1c levels and to reach lower A1c targets.

IN PRACTICE:

"In this real-world study of people with type 2 diabetes, sustained treatment with GLP-1 RAs was associated with greater HbA1c [A1c] improvement compared to DPP-4is [DPP-4 inhibitors] both short and long term, with consistent effects across patient subgroups and varying definitions of improvement," the authors wrote.

SOURCE:

This study was led by Kathrine Kold Sørensen, PhD, Steno Diabetes Center Copenhagen, Copenhagen, Denmark. It was published online on February 25, 2026, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The observed effect of GLP-1 drugs may have been partly due to improved BMI, which the study did not capture. Exposure was defined as at least one redeemed prescription in each 6‑month interval, which could have misclassified brief or minimal use as sustained use. The analysis pooled all GLP-1 drugs and doses rather than examining specific drugs or dose levels, although their effects might differ.

DISCLOSURES:

This study was funded by the European Union and the UK Research and Innovation. One author reported receiving lecture fees from Novo Nordisk and Sanofi and serving on advisory boards of Novo Nordisk and Tandem; another author reported receiving lecture fees from Novo Nordisk.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.