In the GRADE randomized trial, liraglutide and three other diabetes drugs showed differences in ECG abnormalities and cardiac autonomic neuropathy over 4 years.
4,769 participantsGRADE randomized trial comparing ECG outcomes across 4 diabetes drug arms over 4 years
What the researchers found
Different glucose-lowering drugs showed varying effects on ECG abnormalities and cardiac autonomic neuropathy prevalence over 4 years in the GRADE trial.
Why it matters
Heart rhythm problems and autonomic neuropathy are underrecognized diabetes complications — knowing which drugs affect them matters for treatment selection.
The numbers in context
N=4,769; baseline ECG abnormalities 57.1%; baseline CAN 52.8%; year 4 major ECG abnormalities: liraglutide 9% vs non-liraglutide 13% (P=0.03).
How the study worked
Randomized controlled trial (GRADE) with resting ECGs and heart rate variability analysis at baseline, 2, and 4 years in 4,769 participants.
Who was studied
Adults with type 2 diabetes <10 years on metformin (mean age 57.2, 36.3% women)
What this study cannot tell us
ECG analysis was a secondary outcome of the GRADE trial — not powered specifically for this comparison.
How to read the evidence
Substudy of a large randomized controlled trial — high-quality design but ECG outcomes were secondary endpoints.
When this study was published
Published in 2025 in Diabetes Care, part of the ongoing GRADE trial publications.
The bigger picture
GRADE is one of the largest comparative diabetes drug trials, and this cardiac substudy adds important safety and efficacy data beyond glycemic control.
Questions still open
- Does liraglutide have specific cardioprotective effects on autonomic function?
- Should ECG monitoring be routine when choosing between diabetes drugs?
Common questions
Do diabetes drugs affect heart rhythm?
What is cardiac autonomic neuropathy?
Read the original research
Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort.
Diabetes care, 48(11), 1960-1970
Citation
Pop-Busui, Rodica; Rosin, Samuel P; Butera, Nicole M; Krause-Steinrauf, Heidi; Abou Assi, Hiba; Garg, Rajesh K; Inzucchi, Silvio E; Katona, Aimee; McGill, Janet B; Mudaliar, Sunder; Schade, David S; Seaquist, Elizabeth R; Tiktin, Margaret; Soliman, Elsayed Z; Green, Jennifer B. (2025). Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort.. Diabetes care, 48(11), 1960-1970. https://doi.org/10.2337/dc25-1087