Once-Weekly Semaglutide bests Sitagliptin for blood sugar, Weight, and Lipid Profile control in T2DM: Study

The findings, published in the International Journal of Molecular Sciences, are the result of a 52-week randomized clinical trial led by László Imre Tóth and colleagues from the Division of Metabolism, Department of Internal Medicine, University of Debrecen, Hungary. The study compared the effects of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in individuals with type 2 diabetes mellitus (T2DM).

A total of 34 obese adults with T2DM were enrolled and randomized to receive either once-weekly subcutaneous semaglutide (n=18) or once-daily oral sitagliptin (n=16). An additional 31 age- and weight-matched non-diabetic individuals were included as controls. The study primarily assessed changes in glycemic control, anthropometric measurements, and detailed lipoprotein subfractions using Lipoprint gel electrophoresis.

The study revealed the following findings:

• Participants who received semaglutide showed significant reductions in body mass index (BMI), waist circumference, and HbA1c levels, indicating effective control over both weight and blood sugar.
• Semaglutide induced favorable changes in lipid profiles, including notable reductions in low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol.
• The treatment also led to a selective decrease in small, dense LDL particles, which are known to be highly atherogenic and associated with increased cardiovascular risk.
• Semaglutide was found to increase the proportion of larger HDL particles, which are considered protective against heart disease, thereby contributing to a more cardioprotective lipid profile.
• These combined effects suggest that semaglutide promotes a comprehensive shift in lipid metabolism, favoring a profile associated with reduced cardiovascular risk in patients with type 2 diabetes.
• Individuals treated with sitagliptin experienced only modest improvements in blood sugar control and weight, without significant impact on lipid subfractions or inflammatory markers.
• This stark difference highlights the broader metabolic and cardioprotective advantages of semaglutide over DPP-4 inhibitors like sitagliptin.
• Multivariate regression analysis revealed that changes in lipoprotein subfractions following semaglutide treatment were not correlated with changes in BMI or HbA1c.
• This finding suggests that semaglutide may have direct, independent effects on lipid remodeling processes, beyond its influence on weight and glucose control.

The authors emphasize that semaglutide may play a critical role in managing not just glycemic control, but also broader cardiometabolic risks associated with type 2 diabetes. By promoting a healthier lipid profile, it may contribute to lowering cardiovascular disease risk in this population.

"These findings highlight the therapeutic potential of semaglutide in addressing multiple facets of T2DM and support further research into its long-term cardiovascular benefits across diverse patient populations," the authors concluded.

Reference:

Tóth, L. I., Harsányi, A., Csiha, S., Molnár, Á., Lőrincz, H., Nagy, A. C., Paragh, G., Harangi, M., & Sztanek, F. (2024). Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study. International Journal of Molecular Sciences, 26(13), 5951. https://doi.org/10.3390/ijms26135951