Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study
Abstract
1. Introduction
2. Results
2.1. Baseline Clinical and Laboratory Parameters in Enrolled Subjects
2.2. Changes in Clinical and Laboratory Parameters After a 52-Week Semaglutide Treatment in Type 2 Diabetic Patients
2.3. Changes in Clinical and Laboratory Parameters After a 52-Week Sitagliptin Treatment in Type 2 Diabetic Patients
2.4. Multivariate Linear Regression Model to Analyze Changes in Lipid Subfractions Induced by Semaglutide Treatment
3. Discussion
4. Materials and Methods
4.1. Study Design and Participants
4.2. Blood Sampling
4.3. Lipoprotein Subfraction Analyses
4.4. Statistical Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ABCA1 | ATP-binding cassette transporter 1 |
ALT | Alanine transaminase |
AMPK | Adenosine monophosphate-activated protein kinase |
ANOVA | Analysis of variance |
apoA1 | Apolipoprotein A1 |
apoB | Apolipoprotein B100 |
AST | Aspartate transaminase |
AUC | Area under the curve |
BMI | Body mass index |
DPP-4 | Dipeptidyl peptidase-4 |
eGFR | Estimated glomerular filtration rate |
GGT | Gamma-glutamyl transferase |
GLP-1 | Glucagon-like peptide-1 |
GLP-1RA | Glucagon-like peptide-1 receptor agonist |
HbA1c | Hemoglobin A1c |
HDL | High-density lipoprotein |
hsCRP | High-sensitivity C-reactive protein |
IKEB | Local ethics committee |
LDL | Low-density lipoprotein |
PREVEND | Prevention of Renal and Vascular End-stage Disease |
RKEB | Regional ethics committee |
sdLDL | Small-dense low-density lipoprotein |
STEP | Semaglutide Treatment Effect in People with Obesity |
SUSTAIN | Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes |
T2DM | Type 2 diabetes mellitus |
VLDL | Very low-density lipoprotein |
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Patients with T2DM | Controls | ||
---|---|---|---|
Semaglutide Group (Before Treatment) | Sitagliptin Group (Before Treatment) | ||
Sex (male/female) | 18 (12/6) | 16 (7/9) | 31 (10/21) |
Age (year) | 57.9 ± 10.6 | 59.4 ± 11.9 | 55.2 ± 5.0 |
BMI (kg/m2) | 37.96 ± 10.64 | 31.26 ± 2.75 | 37.89 ± 9.64 |
Waist circumference (cm) | 126.4 ± 21.8 | 126.6 ± 25.1 | 114.8 ± 21.0 |
Glucose (mmol/L) | 8.1 (7.10–11.80) # | 8.90 (7.60–10.80) § | 5.35 (4.95–6.05) |
Fructosamine (mmol/L) | 322.39 ± 87.95 # | 299.00 ± 68.80 § | 239.35 ± 55.37 |
HbA1c (%) | 8.1 ± 1.7 # | 8.1 ± 1.3 § | 6.0 ± 1.3 |
Insulin (mU/L) | 19.4 (15.2–27.5) | 26.2 (20.5–41.6) § | 13.7 (8.9–19.8) |
C-peptide (pmol/L) | 1370 (1270–1800) # | 1430 (1140–2730) § | 826.5 (502–976) |
Creatinine (µmol/L) | 78.50 ± 15.07 | 71.47 ± 10.18 | 68.41 ± 15.21 |
eGFR (mL/min/1.73 m2) | 87 (74–90) | 90 (73–90) | 90 (89–90) |
hsCRP (mg/L) | 2.3 (1.7–5.8) # | 5.5 (2.9–13.8) | 11.6 (3.0–18.0) |
AST (U/L) | 21 (16–25) | 27 (21–35) | 20.5 (17–24) |
ALT (U/L) | 24 (17–37) | 34 (23–46) | 25 (16–37) |
GGT (U/L) | 33 (24–49) | 38 (22–87) | 27 (18–39) |
Triglyceride (mmol/L) | 1.72 (1.50–3.11) | 2.00 (1.30–3.40) | 1.70 (1.0–2.28) |
Total cholesterol (mmol/L) | 5.49 ± 1.36 | 5.85 ± 2.24 | 5.14 ± 0.99 |
HDL cholesterol (mmol/L) | 1.27 ± 0.30 | 1.34 ± 0.52 | 1.30 ± 0.32 |
Non-HDL cholesterol (mmol/L) | 3.98 ± 0.95 | 4.09 ± 1.95 | 3.58 ± 1.29 |
LDL cholesterol (mmol/L) | 3.13 ± 0.88 | 3.28 ± 1.51 | 3.28 ± 0.84 |
ApoA1 (g/L) | 1.55 ± 0.24 | 1.62 ± 0.33 | 1.59 ± 0.27 |
ApoB (g/L) | 1.03 ± 0.28 | 1.26 ± 0.50 | 1.04 ± 0.25 |
Large LDL {1–2} (mmol/L) | 1.37 (1.14–1.48) | 1.45 (1.17–2.25) | 1.49 (1.18–1.62) |
Small LDL {3–7} (mmol/L) | 0.1 (0.05–0.22) | 0.1 (0–0.21) | 0.0 (0.0–0.09) |
Mean LDL size (nm) | 27.0 (26.5–27.1) | 27.0 (26.6–27.3) | 27.3 (27.0–27.4) |
Large HDL {1–3} (mmol/L) | 0.25 (0.17–0.28) | 0.25 (0.16–0.39) | 0.29 (0.22–0.36) |
Intermediate HDL {4–7} (mmol/L) | 0.58 (0.5–0.68) | 0.56 (0.47–0.67) | 0.62 (0.50–0.73) |
Small HDL {8–10} (mmol/L) | 0.41 (0.31–0.47) | 0.39 (0.32–0.44) | 0.39 (0.27–0.52) |
Baseline | Week 26 | Week 52 | |
---|---|---|---|
BMI (kg/m2) | 37.96 ± 10.64 | 35.28 ± 9.43 † | 34.88 ± 10.22 § |
Waist circumference (cm) | 126.4 ± 21.8 | 119.7 ± 21.6 † | 115.5 ± 20.9 § |
Glucose (mmol/L) | 8.1 (7.1–11.8) | 7.5 (5.0–8.6) † | 7.7 (5.3–10.4) § |
Fructosamine (mmol/L) | 322.4 ± 87.9 | 260.4 ± 39.2 † | 251.5 ± 37.7 § |
HbA1c (%) | 8.08 ± 1.65 | 6.86 ± 1.12 † | 6.57 ± 0.95 § |
Insulin (mU/L) | 19.4 (15.2–27.5) | 21.6 (12.3–28.1) | 19.3 (9.1–30.2) |
C-peptide (pmol/L) | 1370 (1270–1800) | 1340 (733–2110) | 1240 (1040–1610) |
Creatinine (µmol/L) | 78.50 ± 15.07 | 77.94 ± 30.64 | 71.56 ± 16.67 |
eGFR (mL/min/1.73 m2) | 86.5 (74–90) | 90 (78–90) | 90 (84–90) |
hsCRP (mg/L) | 2.3 (1.7–5.8) | 2.30 (1.30–6.26) | 2.10 (1.10–2.40) |
AST (U/L) | 21 (17–25) | 20.5 (14–28) | 17 (15–26) |
ALT (U/L) | 27 (21–37) | 26 (18–32) | 21 (16–31) |
GGT (U/L) | 34 (27–56) | 33 (23–45) | 35 (22–50) |
Triglyceride (mmol/L) | 1.72 (1.50–3.11) | 1.575 (1.00–2.17) | 1.585 (1.0–2.50) |
Total cholesterol (mmol/L) | 5.49 ± 1.36 | 4.83 ± 1.31 | 4.79 ± 1.00 |
HDL cholesterol (mmol/L) | 1.27 ± 0.30 | 1.40 ± 0.37 † | 1.43 ± 0.38 § |
Non-HDL cholesterol (mmol/L) | 3.98 ± 0.95 | 3.34 ± 1.08 | 3.35 ± 0.82 § |
LDL cholesterol (mmol/L) | 3.13 ± 0.88 | 2.85 ± 1.06 | 2.72 ± 0.84 § |
Mean LDL size (nm) | 27.0 (26.5–27.1) | 27.2 (27.1–27.3) † | 27.1 (26.9–27.3) § |
Large LDL {1–2} (mmol/L) | 1.37 (1.14–1.48) | 1.17 (0.9–1.7) # | 1.28 (1–1.5) § |
Small LDL {3–7} (mmol/L) | 0.1 (0.05–0.2) | 0.02 (0–0.1) # | 0.06 (0–0.1) § |
Large HDL {1–3} (mmol/L) | 0.25 (0.2–0.3) | 0.27 (0.2–0.4) # | 0.24 (0.2–0.3) |
Intermediate HDL {4–7} (mmol/L) | 0.58 (0.5–0.7) | 0.66 (0.6–0.8) # | 0.66 (0.6–0.7) § |
Small HDL {8–10} (mmol/L) | 0.41 (0.3–0.5) | 0.41 (0.3–0.5) | 0.41 (0.3–0.5) |
ApoA1 (g/L) | 1.55 ± 0.24 | 1.49 ± 0.23 | 1.54 ± 0.27 |
ApoB (g/L) | 1.03 ± 0.28 | 0.96 ± 0.31 | 0.99 ± 0.25 |
Baseline | Week 26 | Week 52 | |
---|---|---|---|
BMI (kg/m2) | 31.26 ± 2.75 | 31.10 ± 2.98 | 30.911 ± 2.9 § |
Waist circumference (cm) | 126.60 ± 25.08 | 125.25 ± 29.18 | 124.25 ± 29.58 |
Glucose (mmol/L) | 8.90 (7.60–10.80) | 7.50 (5–7.9) † | 8.00 (5.7–9.3) |
Fructosamine (mmol/L) | 299.0 ± 68.8 | 262.6 ± 51.2 | 253.4 ± 28.7 § |
HbA1c (%) | 8.13 ± 1.29 | 6.91 ± 0.95 † | 7.11 ± 1.07 § |
Insulin (mU/L) | 26.2 (20.5–41.6) | 26.0 (18.7–40.2) | 21.95 (12.5–26.5) |
C-peptide (pmol/L) | 1430 (1140–2730) | 1870 (966–2020) | 1110 (904.5–1675) |
Creatinine (µmol/L) | 71.47 ± 10.18 | 70.571 ± 15.301 | 71.20 ± 14.26 |
eGFR (ml/min/1.73 m2) | 90 (73–90) | 90 (85–90) | 90 (85–90) |
hsCRP (mg/L) | 5.5 (2.9–13.8) | 4.7 (2.3–11.7) | 8.7 (2.4–14.7) |
AST (U/L) | 27 (21–35) | 23 (18–32) | 28.5 (16–36) |
ALT (U/L) | 34 (23–46) | 29.5 (21–43) | 36 (25–46) |
GGT (U/L) | 38 (22–87) | 39 (20–52) | 39 (25–44) |
Triglyceride (mmol/L) | 2.00 (1.30–3.40) | 2.08 (1.55–2.9) | 1.850 (1.3–3.1) |
Total cholesterol (mmol/L) | 5.85 ± 2.24 | 5.264 ± 1.32 | 5.31 ± 1.57 |
HDL cholesterol (mmol/L) | 1.34 ± 0.52 | 1.303 ± 0.44 | 1.338 ± 0.34 |
Non-HDL cholesterol (mmol/L) | 4.09 ± 1.95 | 3.962 ± 1.34 | 4.00 ± 1.52 |
LDL cholesterol (mmol/L) | 3.28 ± 1.51 | 3.092 ± 1.08 | 3.209 ± 1.2 |
Mean LDL size (nm) | 27.0 (26.6–27.3) | 27.1 (26.7–27.2) | 27.0 (26.7–27.3) |
Large LDL {1–2} (mmol/L) | 1.45 (1.17–2.3) | 1.47 (1.2–1.6) | 1.4 (1.3–1.9) |
Small LDL {3–7} (mmol/L) | 0.1 (0–0.2) | 0.07 (0–0.2) | 0.09 (0–0.1) |
Large HDL {1–3} (mmol/L) | 0.25 (0.2–0.4) | 0.24 (0.1–0.4) | 0.28 (0.2–0.4) |
Intermediate HDL {4–7} (mmol/L) | 0.56 (0.5–0.7) | 0.54 (0.4–0.7) | 0.59 (0.58–0.8) |
Small HDL {8–10} (mmol/L) | 0.39 (0.3–0.4) | 0.37 (0.3–0.5) | 0.39 (0.35–0.43) |
ApoA1 (g/L) | 1.62 ± 0.33 | 1.528 ± 0.39 † | 1.484 ± 0.34 § |
ApoB (g/L) | 1.26 ± 0.50 | 1.10 ± 0.4 | 1.197 ± 0.41 |
ΔBMI * | p-Value | |
---|---|---|
Δ Large LDL {1–2} (mmol/L) | 0.01 | 0.680 |
Δ Small LDL {3–7} (mmol/L) | −0.03 | 0.390 |
Δ Mean LDL size (nm) | 0.23 | 0.534 |
Δ Large HDL {1–3} (mmol/L) | 0.23 | 0.534 |
Δ Intermediate HDL {4–7} (mmol/L) | 0.01 | 0.310 |
Δ Small HDL {8–10} (mmol/L) | 0.01 | 0.310 |
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Tóth, L.I.; Harsányi, A.; Csiha, S.; Molnár, Á.; Lőrincz, H.; Nagy, A.C.; Paragh, G.; Harangi, M.; Sztanek, F. Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study. Int. J. Mol. Sci. 2025, 26, 5951. https://doi.org/10.3390/ijms26135951
Tóth LI, Harsányi A, Csiha S, Molnár Á, Lőrincz H, Nagy AC, Paragh G, Harangi M, Sztanek F. Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study. International Journal of Molecular Sciences. 2025; 26(13):5951. https://doi.org/10.3390/ijms26135951
Chicago/Turabian StyleTóth, László Imre, Adrienn Harsányi, Sára Csiha, Ágnes Molnár, Hajnalka Lőrincz, Attila Csaba Nagy, György Paragh, Mariann Harangi, and Ferenc Sztanek. 2025. "Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study" International Journal of Molecular Sciences 26, no. 13: 5951. https://doi.org/10.3390/ijms26135951
APA StyleTóth, L. I., Harsányi, A., Csiha, S., Molnár, Á., Lőrincz, H., Nagy, A. C., Paragh, G., Harangi, M., & Sztanek, F. (2025). 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