The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment
Abstract
:1. Introduction
2. Pathophysiological Link Between MASLD, T2DM and CVD
2.1. Genetic Factors
2.2. Insulin Resistance, Lipotoxicity
2.3. Inflammation, Cytokines, Oxidative Stress
2.4. ΜAFLD and CVD
2.5. The Gut Microbiota
3. Monitoring Patients with ΜASLD
4. Current Therapeutic Approaches for Managing NAFLD-MASLD, T2DM, and CVD Risk Factors
4.1. Lifestyle Modifications
4.2. Vitamin E
4.3. Lipid-Lowering Therapies
4.4. Blood Pressure Control
4.5. Metformin: The First-Line Drug
4.6. GLP-1 Receptor Agonists
4.7. SGLT2 Inhibitors
4.8. Combination Therapy GLP-1 Receptor Agonists/SGLT2 Inhibitors
4.9. Pioglitazone
4.10. DPP-4 Inhibitors
4.11. Bariatric Surgery
4.12. Other Therapeutic Targets
5. Discussion
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Steatosis | Liver Enzymes | Inflammation | CV Risk | |
---|---|---|---|---|
PUFAs | Decreased | Decreased | Decreased | Decreased |
Statins | Decreased | Unknown/Increased | Decreased | Decreased |
Fibrates | Unknown/Unchanged | Unknown/Unchanged | Decreased | Decreased |
Weight | Steatosis | Liver Enzymes | CV Risk | Inflammation | Side Effects | ||
---|---|---|---|---|---|---|---|
Metformin | TONIC (173 patients) (Randomized double-blind, double-dummy, placebo-controlled trial) (1000 mg metformin/day, 800 IU Vitamin E/Day for 96 weeks) HOME (745 patients) (Randomized, placebo-controlled trial) (850 mg metformin/day, for 16 weeks) | Decreased | Decreased | Decreased /Unchanged | Decreased | Decreased | Gastrointestinal effects, lactic acidosis |
GLP-1 RAs | AWARD (810 patients) (Open-label, randomized trial) (Dulaglutide 1.5 mg/week, dulaglutide 0.5 mg/week, insulin glarine daily for 52 weeks) LEAN (52 patients) (Double-blinded, placebo-controlled randomized trial) (Liraglutide 1.8 mg/daily for 48 weeks) SUSTAIN9 (302 patients) (Randomized, placebo-controlled trial) (Escalating to 1 mg semaglutide for 30 weeks) | Decreased | Decreased | Decreased | Decreased | Decreased | Gastrointestinal effects, pancreatitis, risks for cancer |
SGLT2 inhibitors | EFFECT II (84 patients) (Double-blind randomized placebo-controlled) (Dapagliflozin 10 mg/day + 4 g omega-3 carboxylic acids for 12 weeks) E-LIFT (50 patients) (Randomized controlled trial) (Empagliflozin 10 mg/day > 12 weeks) EMPA-REG-OUTCOME (7020 patients) (10–25 mg empagliflozin/daily for 2.6 years) | Decreased | Decreased | Decreased | Decreased | Decreased | Glycosuria, cardiovascular concern, ketoacidosis, hypotension, bone fracture |
DPP-4inhibitors | SAVOR-TIMI (16,492 patients) (Randomized, double-blind, placebo-controlled trial) (Saxagliptin 2.5–5 mg/day for 18 months) | Unchanged | Decrease/Unchanged | Decreased/ Unchanged | Decreased /Unchanged | Unchanged | Pancreatitis, risks for cancer, acute hepatitis and kidney impairment |
Thiazolidinediones | Pro/active (952 patients) (Randomized study) (15–45 mg/day pioglitazone depending on tolerance) PERISCOPE (543 patients) (Randomized controlled trial) (15–45 mg pioglitazone/day for 18 months) | Increased | Decreased | Decreased/ Unchanged | Decreased | Decreased | Hepatitis, bladder cancer, water retention and weight gain |
Bariatric Surgery | Decreased | Decreased | Decreased/ Unchanged | Decreased | Decreased /Unchanged | Depending on the type of surgery: indigestion, sagging skin, stomach ulcers, nausea, gall stones |
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Michalopoulou, E.; Thymis, J.; Lampsas, S.; Pavlidis, G.; Katogiannis, K.; Vlachomitros, D.; Katsanaki, E.; Kostelli, G.; Pililis, S.; Pliouta, L.; et al. The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment. J. Clin. Med. 2025, 14, 428. https://doi.org/10.3390/jcm14020428
Michalopoulou E, Thymis J, Lampsas S, Pavlidis G, Katogiannis K, Vlachomitros D, Katsanaki E, Kostelli G, Pililis S, Pliouta L, et al. The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment. Journal of Clinical Medicine. 2025; 14(2):428. https://doi.org/10.3390/jcm14020428
Chicago/Turabian StyleMichalopoulou, Eleni, John Thymis, Stamatios Lampsas, George Pavlidis, Konstantinos Katogiannis, Dimitrios Vlachomitros, Eleni Katsanaki, Gavriella Kostelli, Sotirios Pililis, Loukia Pliouta, and et al. 2025. "The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment" Journal of Clinical Medicine 14, no. 2: 428. https://doi.org/10.3390/jcm14020428
APA StyleMichalopoulou, E., Thymis, J., Lampsas, S., Pavlidis, G., Katogiannis, K., Vlachomitros, D., Katsanaki, E., Kostelli, G., Pililis, S., Pliouta, L., Kountouri, A., Papanikolaou, I. S., Lambadiari, V., & Ikonomidis, I. (2025). The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment. Journal of Clinical Medicine, 14(2), 428. https://doi.org/10.3390/jcm14020428