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Randomized Controlled Trial
. 2025 Jun 20;26(13):5951.
doi: 10.3390/ijms26135951.

Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study

László Imre Tóth  1   2 , Adrienn Harsányi  1 , Sára Csiha  2   3 , Ágnes Molnár  1 , Hajnalka Lőrincz  1 , Attila Csaba Nagy  4 , György Paragh  1 , Mariann Harangi  1   5   6 , Ferenc Sztanek  1
Affiliations
Randomized Controlled Trial

Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study

László Imre Tóth et al. Int J Mol Sci. .

Abstract

Recent studies have demonstrated the efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in enhancing glycemic control, regulating body weight, and modulating lipid metabolism. However, their effects on lipoprotein subfractions have not been clarified. The objective of this 52-week, single-center, randomized trial was to compare the effects of subcutaneous semaglutide administered once weekly and oral sitagliptin administered once daily on anthropometric measurements and lipoprotein subfractions measured by Lipoprint gelelectrophoresis in patients with type 2 diabetes mellitus (T2DM). A total of 34 obese individuals with T2DM were enrolled in the study and randomly assigned to receive semaglutide (n = 18) or sitagliptin (n = 16). Thirty-one age- and body weight-matched non-diabetic obese individuals served as controls. Semaglutide treatment resulted in significant reductions in body mass index (BMI), waist circumference, and HbA1c, along with improvements in lipid parameters, including reductions in LDL cholesterol and non-HDL cholesterol levels, and redistribution of LDL and HDL subfractions toward a less atherogenic profile. Conversely, sitagliptin elicited modest glycemic improvements without substantial alterations in lipid composition. Multivariate regression analysis demonstrated that fluctuations in lipoprotein subfractions were not influenced by changes in BMI or HbA1c. These results support the pleiotropic metabolic benefits of semaglutide and its potential role in managing the cardiometabolic risk of T2DM.

Keywords: GLP-1 receptor agonist; cardiometabolic risk; lipoprotein subfractions; semaglutide; sitagliptin; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The distribution of lipoprotein subfractions in type 2 diabetic patients during a 52-week semaglutide (A) and sitagliptin treatment (B). The distribution of lipoprotein subfractions was analyzed using a Lipoprint gel electrophoresis system. Abbreviations: IDL, intermediate density lipoprotein; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.
Figure 2
Figure 2
The distribution of high-density lipoprotein (HDL) subfractions in type 2 diabetic patients during a 52-week semaglutide (A) and sitagliptin treatment (B). The distribution of HDL subfractions was analyzed using a Lipoprint gel electrophoresis system.
Figure 3
Figure 3
The flowchart of study design. Abbreviations: T2DM, type 2 diabetes mellitus; sc., subcutaneous; po., per os.
See this image and copyright information in PMC

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