GLP-1 RAs Superior to Metformin for Blood Sugar Control, Yet Metformin Shows Higher Adherence in Prediabetes: Study

The research, published in the Journal of Diabetes, revealed that GLP-1 receptor agonists were linked to a lower likelihood of requiring additional glucose-lowering medications and demonstrated superior control of glycated hemoglobin levels overall. However, in patients with prediabetes, metformin was associated with higher rates of treatment adherence.

GLP-1 RAs are increasingly being prescribed in drug-naive patients. Kathrine Kold Sørensen, Department of Cardiology, Nordsjælland Hospital, Hillerød, Denmark, and colleagues aimed to compare add-on therapy, adherence, and changes in biomarkers one year after starting treatment with either GLP-1 receptor agonists or metformin.

For this purpose, the researchers utilized Danish nationwide registers to include new users of GLP-1 receptor agonists or metformin from 2018 to 2021, specifically those with glycated hemoglobin (HbA1c) levels of ≥42 mmol/mol. GLP-1 RA initiators were matched to metformin initiators in a 1:1 ratio to evaluate outcomes in both prediabetes and diabetes.

The main outcomes analyzed included the one-year risk of requiring additional glucose-lowering medications and the one-year risk of non-adherence. One-year risks were estimated using multiple logistic regression and standardized methods, while multiple linear regression was applied to assess average differences in changes to biomarkers.

Based on the study, the researchers reported the following findings:

• The study included 1,778 individuals initiating treatment with GLP-1 receptor agonists or metformin.
• After adjusting for various factors, GLP-1 RA was linked to a lower one-year risk of requiring additional glucose-lowering treatment in patients with prediabetes (one-year risk ratio [RR]: 0.27) and diabetes (RR: 0.67).
• Among patients with prediabetes, GLP-1 RA was associated with a higher one-year risk of nonadherence (RR: 1.60), while there was no significant difference in patients with diabetes (RR: 0.88).
• Compared to metformin, GLP-1 RA was associated with greater reductions in HbA1c levels, with a decrease of −2.59 mmol/mol for prediabetes and −3.79 mmol/mol for diabetes.

The findings indicated that in patients with prediabetes, starting treatment with GLP-1 receptor agonists was linked to a reduced risk of needing additional glucose-lowering therapy compared to metformin. However, those initiating metformin demonstrated significantly higher levels of adherence.

"In patients with diabetes, GLP-1 RA initiation similarly resulted in a lower risk of requiring extra glucose-lowering therapy, but there was no difference in nonadherence rates when compared to metformin initiation," the researchers wrote.

Reference:

Sørensen, K. K., Gerds, T. A., Køber, L., Fosbøl, E. L., Poulsen, H. E., Møller, A. L., Andersen, M. P., Pedersen-Bjergaard, U., Torp-Pedersen, C., & Zareini, B. (2024). Comparing Glucagon-like peptide-1 receptor agonists versus metformin in drug-naive patients: A nationwide cohort study. Journal of Diabetes, 16(10), e70000. https://doi.org/10.1111/1753-0407.70000