Incretin‐based therapies for the management of cardiometabolic disease in the clinic: Past, present, and future

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 45(1), P. 29 - 65

Published: Aug. 14, 2024

Among newer classes of drugs for type 2 diabetes mellitus (T2DM), glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are incretin-based agents that lower both blood sugar levels and promote weight loss. They do so by activating pancreatic GLP-1 receptors (GLP-1R) to glucose-dependent insulin release inhibit glucagon secretion. also act on in the brain gastrointestinal tract suppress appetite, slow gastric emptying, delay glucose absorption. Phase 3 clinical trials have shown RAs improve cardiovascular outcomes setting T2DM or overweight/obesity people who have, at high risk having atherosclerotic disease. This is largely driven reductions ischemic events, although emerging evidence supports benefits other conditions, such as heart failure with preserved ejection fraction. The success has seen evolution incretin therapies. Tirzepatide emerged a dual insulinotropic polypeptide (GIP)/GLP-1 RA, more striking effects glycemic control reduction than those achieved isolated GLP-1R agonism alone. consists lowering glycated hemoglobin 2% loss exceeding 15% from baseline. Here, we review pharmacological properties tirzepatide discuss their effectiveness overweight/obesity, including ability reduce adverse outcomes. We delve into mechanistic basis these cardioprotective consider next steps implementing existing future therapies broader management cardiometabolic

Language: Английский

---

Estimating the Prevalence and Characteristics of Patients Potentially Eligible for Lipoprotein(a)-Lowering Therapies in a Real-World Setting

Biomedicines, Journal Year: 2023, Volume and Issue: 11(12), P. 3289 - 3289

Published: Dec. 12, 2023

High lipoprotein(a) (Lp(a)) plasma levels are significantly associated with an increased risk of developing atherosclerotic cardiovascular diseases (ASCVD). The aim this analysis was to estimate the prevalence and characteristics patients potentially eligible for Lp(a)-lowering therapies in a real-world setting (i.e., ASCVD Lp(a) > 70 mg/dL). For reason, we pooled data from large cohort Italian outpatients (N = 5961; men: 2879, women: 3982) dyslipidemia. A binary logistic regression used determine significant predictors cohort, which were age (Odds Ratio (OR): 1.158, 95% Confidence Interval (CI): 1.114 1.203,

Language: Английский

---

Reduced Oxidative Susceptibility of Lp(a) and LDL Fractions as a Pleiotropic Effect of Lipoprotein Apheresis in Patients with Elevated Lp(a) and ASCVDs

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13597 - 13597

Published: Dec. 19, 2024

Oxidative modifications of lipoproteins play a crucial role in the initiation atherosclerotic cardiovascular diseases (ASCVDs). Nowadays, one effective strategy for treatment patients with hyperlipoproteinemia(a) is lipoprotein apheresis (LA), which has pleiotropic effect on reducing risk ASCVDs. The significance oxidative susceptibility LDL fraction ASCVDs been extensively studied. Whether LA alters lipoprotein(a) to remains an unresolved issue. In this study, we isolated fractions by ultracentrifugation undergoing (LA group) at three time points and who were qualified but did not consent procedure (non-LA group). We performed copper-mediated oxidation Lp(a) determined autotaxin activity. After apheresis, observed lower as expressed extended value lag time, decreased slope curve, final concentration conjugated dienes. No significant differences found between these parameters before 7 days after LA. Additionally, both had correlation activity all characterizing fraction. Our results demonstrate that may be related reduced particles, influence reduction ASCVD apheresis. rebound will contribute better definition frequency guidelines.

Language: Английский

---

Progress of Clinical Research on Lipoprotein a and Cardiovascular Diseases

Advances in Clinical Medicine, Journal Year: 2024, Volume and Issue: 14(02), P. 2320 - 2327

Published: Jan. 1, 2024

Language: Английский

---

Sanghuangporus vaninii extract ameliorates hyperlipidemia in rats by mechanisms identified with transcriptome analysis

Food Science & Nutrition, Journal Year: 2024, Volume and Issue: 12(5), P. 3360 - 3376

Published: Feb. 16, 2024

Abstract The increasing incidence of hyperlipidemia is a serious threat to public health. development effective and safe lipid‐lowering drugs with few side effects necessary. purpose this study was assess the activity Sanghuangporus vaninii extract (SVE) in rat experiments reveal molecular mechanism by transcriptome analysis. Hyperlipidemia induced animals using high‐fat diet for 4 weeks. At end 4th week, hyperlipidemic rats were assigned into two control groups (model positive simvastatin control) three treatment that received SVE at 200, 400, or 800 mg kg −1 day another A last group comprised normal chow‐fed rats. 8th sacrificed lipid serum levels, histopathology, liver profiles determined. demonstrated relieve disorder improve histopathological changes dose‐dependent manner. transcriptomic analysis identified hepatocyte gene major pathways including steroid biosynthesis, bile secretion, cholesterol metabolism, AMPK signaling, thyroid hormone glucagon signaling. changed expression crucial genes different confirmed qPCR. Collectively, revealed could rats, might be promote metabolism lipids excretion cholesterol, inhibit biosynthesis activating signaling pathway, pathway.

Language: Английский

---

Niacin Intake Associated with Cardiovascular Disease and Mortality in Chronic Kidney Disease Patients: Evidence from a Prospective Study

Published: Jan. 1, 2024

Language: Английский

---