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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.

Publication ,  Journal Article
Pop-Busui, R; Rosin, SP; Butera, NM; Krause-Steinrauf, H; Abou Assi, H; Garg, RK; Inzucchi, SE; Katona, A; McGill, JB; Mudaliar, S; Schade, DS ...
Published in: Diabetes Care
November 1, 2025

OBJECTIVE: To describe the prevalence and incidence of electrocardiogram (ECG) abnormalities and ECG-derived cardiovascular autonomic neuropathy (CAN) in the GRADE cohort of adults with type 2 diabetes (T2D) <10 years. RESEARCH DESIGN AND METHODS: Individuals with T2D taking metformin alone were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Resting ECGs were completed at the baseline, 2-year, and 4-year study visits and analyzed for minor and major abnormalities and CAN assessed with heart rate variability (HRV) in 4,769 participants. Incidence of new major, minor, and any ECG abnormalities and CAN by treatment group was analyzed using logistic repeated-measures models at years 2 and 4 adjusted for baseline risk factors. RESULTS: At baseline, participants were a mean age of 57.2 ± 10.0 years, 36.3% were women, mean diabetes duration was 4.3 ± 2.8 years, and mean HbA1c was 7.5 ± 0.5%. Participants with ECG abnormalities at baseline (57.1%) and ECG-derived CAN (52.8%) were older and had more severe cardiovascular risk factors. The incidence of minor and major ECG abnormalities was similar among all treatment groups. However, at year 4, major ECG abnormalities were fewer in the liraglutide versus nonliraglutide groups (9% vs. 13%; P = 0.03). The incidence of CAN did not differ between the liraglutide and nonliraglutide groups across visits (P = 0.42); however, one measure of HRV (SD of normal-to-normal R-R intervals) was higher at year 2 in the liraglutide versus nonliraglutide groups (P = 0.02). CONCLUSIONS: ECG abnormalities, including those reflecting CAN, are common in individuals with T2D <10 years and more so in those with certain cardiovascular risk factors. The development of major ECG abnormalities may be lower with liraglutide.

Duke Scholars

Published In

Diabetes Care

DOI

EISSN

1935-5548

Publication Date

November 1, 2025

Volume

48

Issue

11

Start / End Page

1960 / 1970

Location

United States

Related Subject Headings

  • Sulfonylurea Compounds
  • Sitagliptin Phosphate
  • Prevalence
  • Middle Aged
  • Metformin
  • Male
  • Liraglutide
  • Insulin Glargine
  • Incidence
  • Hypoglycemic Agents
 

Citation

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Pop-Busui, R., Rosin, S. P., Butera, N. M., Krause-Steinrauf, H., Abou Assi, H., Garg, R. K., … GRADE Research Group. (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
Pop-Busui, Rodica, Samuel P. Rosin, Nicole M. Butera, Heidi Krause-Steinrauf, Hiba Abou Assi, Rajesh K. Garg, Silvio E. Inzucchi, et al. “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, no. 11 (November 1, 2025): 1960–70. https://doi.org/10.2337/dc25-1087.
Pop-Busui R, Rosin SP, Butera NM, Krause-Steinrauf H, Abou Assi H, Garg RK, Inzucchi SE, Katona A, McGill JB, Mudaliar S, Schade DS, Seaquist ER, Tiktin M, Soliman EZ, Green JB, GRADE Research Group. 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. 2025 Nov 1;48(11):1960–1970.

Published In

Diabetes Care

DOI

EISSN

1935-5548

Publication Date

November 1, 2025

Volume

48

Issue

11

Start / End Page

1960 / 1970

Location

United States

Related Subject Headings

  • Sulfonylurea Compounds
  • Sitagliptin Phosphate
  • Prevalence
  • Middle Aged
  • Metformin
  • Male
  • Liraglutide
  • Insulin Glargine
  • Incidence
  • Hypoglycemic Agents