Sotagliflozin
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Reducción del riesgo de muerte cardiovascular, hospitalización por insuficiencia cardiaca y consulta urgente por insuficiencia cardiaca en adultos con insuficiencia cardiaca o con diabetes tipo 2, enfermedad renal crónica y otros factores de riesgo cardiovascular.
Contraindicaciones
Absolutas
- Hipersensibilidad a sotagliflozina
Advertencias clínicas
- Advertencia mayor · Riesgos relevantes: cetoacidosis, depleción de volumen, urosepsis o pielonefritis, hipoglucemia con insulina o secretagogos, gangrena de Fournier y micosis genitales. — DailyMed INPEFA setid 1a46614e-05f6-421a-b6f4-d6f8760d643a
Interacciones medicamentosas
- ModeradaDigoxina
Mecanismo: Sotagliflozina puede aumentar la exposición a digoxina.
Recomendación: Vigilar las concentraciones de digoxina o la respuesta clínica durante la administración concomitante.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a46614e-05f6-421a-b6f4-d6f8760d643aDailyMed setid 1a46614e-05f6-421a-b6f4-d6f8760d643a
- ModeradaRifampicina y otros inductores de UGT
Mecanismo: Rifampicina puede reducir la exposición a sotagliflozina.
Recomendación: Vigilar la respuesta clínica durante la administración concomitante.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a46614e-05f6-421a-b6f4-d6f8760d643aDailyMed setid 1a46614e-05f6-421a-b6f4-d6f8760d643a
- ModeradaLitio
Mecanismo: Los inhibidores de SGLT2 pueden reducir las concentraciones séricas de litio.
Recomendación: Vigilar las concentraciones séricas de litio con mayor frecuencia al iniciar sotagliflozina y durante los cambios de dosis.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a46614e-05f6-421a-b6f4-d6f8760d643aDailyMed setid 1a46614e-05f6-421a-b6f4-d6f8760d643a
Eventos adversos
Comunes (≥1%)
Infección urinaria · Depleción de volumen · Diarrea · Hipoglucemia · Micosis genital
Raros pero graves
Cetoacidosis · Urosepsis o pielonefritis · Gangrena de Fournier · Lesión renal aguda
Embarazo y lactancia
No se recomienda durante el segundo y tercer trimestre del embarazo ni durante la lactancia.
Bibliografía reciente (PubMed)
Patients with diabetes are at higher risk of cardiovascular diseases and cognitive impairment. SGLT2 inhibitors (Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Sotagliflozin) are newer hypoglycemic agents with many pleiotropic effects. In this review, we discuss their neuroprotective potential. SGLT2 inhibitors (SGLT2i) are lipid-soluble and reach the brain/serum ratio from 0.3 to 0.5. SGLT receptors are present in the central nervous system (CNS). Flozins are not fully SGLT2-selective and have an affinity for the SGLT1 receptor, which is associated with protection against ischemia/reperfusion brain damage. SGLT2i show an anti-inflammatory and anti-atherosclerotic effect, including reduction of proinflammatory cytokines, M2 macrophage polarization, JAK2/STAT1 and NLRP3 inflammasome inhibition, as well as cIMT regression. They also mitigate oxidative stress. SGLT2i improve endothelial function, prevent remodeling and exert a protective effect on the neurovascular unit, blood-brain barrier, pericytes, astrocytes, microglia, and oligodendrocytes. Flozins are also able to inhibit AChE, which contributes to cognitive improvement. Empagliflozin significantly increases the level of cerebral BDNF, which modulates neurotransmission and ensures growth, survival, and plasticity of neurons. Moreover, they may be able to restore the circadian rhythm of mTOR activation, which is quite a novel finding in the field of research on metabolic diseases and cognitive impairment. SGLT2i have a great potential to protect against atherosclerosis and cognitive impairment in patients with type 2 diabetes mellitus.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used to treat diabetes mellitus. Abundant evidence has shown that SGLT2 inhibitors can reduce hospitalization for heart failure (HF) in patients with or without diabetes. An increasing number of studies are being conducted on the mechanisms of action of SGLT2 inhibitors in HF. Our review summarizes a series of clinical trials on the cardioprotective effects of SGLT2 inhibitors in the treatment of HF. We have summarized several classical SGLT2 inhibitors in cardioprotection research, including empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and sotagliflozin. In addition, we provided a brief overview of the safety and benefits of SGLT2 inhibitors. Finally, we focused on the mechanisms of SGLT2 inhibitors in the treatment of HF, including ion-exchange regulation, volume regulation, ventricular remodeling, and cardiac energy metabolism. Exploring the mechanisms of SGLT2 inhibitors has provided insight into repurposing these diabetic drugs for the treatment of HF.
In patients with type 2 diabetes (T2D) and a history of heart failure (HF), sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular (CV) benefits. However, the comparative efficacy of individual SGLT2is remains uncertain. This network meta-analysis (NMA) compared the efficacy and safety of five SGLT2is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) on CV outcomes in these patients. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to September 23, 2022, to identify all randomized controlled trials (RCTs) comparing SGLT2is to placebo in T2D patients with HF. The main outcomes included composite CV death/heart failure hospitalization (HFH), HFH, CV death, all-cause mortality, and adverse events. Pairwise and NMA approaches were applied. Our analysis included 11 RCTs with a total of 20,438 patients with T2D and HF. All SGLT2is significantly reduced HFH compared to standard of care (SoC) alone. "Add-on" SGLT2is, except ertugliflozin, significantly reduced composite CV death/HFH relative to SoC alone. Moreover, canagliflozin had lower composite CV death/HFH compared to dapagliflozin. Based on the surface under the cumulative ranking curve (SUCRA), the top-ranked SGLT2is for reducing HFH were canagliflozin (95.5%), sotagliflozin (66.0%), and empagliflozin (57.2%). Head-to-head comparisons found no significant differences between individual SGLT2is in reducing CV death. "Add-on" SGLT2is reduced all-cause mortality compared with SoC alone, although only dapagliflozin was statistically significant. No SGLT2is were significantly associated with serious adverse events. A sensitivity analysis focusing on HF-specific trials found that dapagliflozin, empagliflozin, and sotagliflozin significantly reduced composite CV death/HFH, consistent with the main analysis. However, no significant differences were identified from their head-to-head comparisons in the NMA. The SUCRA indicated t
Heart failure (HF) is a highly prevalent disease, among the primary factors contributing to morbidity and death. One of its types is heart failure with preserved ejection fraction (HFpEF) comprising 40%-50% of newly diagnosed HF cases. Despite the high prevalence of HFpEF, there is still a lack of knowledge regarding the best drugs and treatment approaches to be used. However, the sodium-glucose co-transporter 2 (SGLT2) inhibitors could be a promising treatment. To examine SGLT2 inhibitors' effect on hospitalization, cardiovascular death, and estimated glomerular filtration rate (eGFR) in HFpEF patients. We conducted searches for randomized controlled trials (RCTs) in PubMed, Embase, Scopus, and Web of Science up to July 2024. We chose RCTs that examined the effects of SGLT2 inhibitors and placebo in individuals with higher than 40% ejection fraction (HFpEF). The methodology for the systematic review and meta-analysis was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We included 8 studies with 16,509 participants. Drugs examined in our paper included empagliflozin, dapagliflozin, sotogliflozin, and ertugliflozin. Various outcomes were analyzed in different papers. However, different SGLT2 inhibitors lead to a decreased risk of cardiovascular hospitalization and kidney injury. Our meta-analysis showed a decreased risk of cardiovascular hospitalization but not death due to cardiovascular causes or other causes. These results were regardless of baseline status of eGFR, systolic blood pressure, atrial fibrillation or flutter, diabetes mellitus, sex, body mass index, and nt-proBNP. The included studies were of moderate to high quality. For individuals with HFpEF, SGLT2 inhibitors have been proven to be a safe and effective medication. However, more studies are needed for longer durations, reporting adverse events, effects on exercise tolerance, and other secondary outcomes.
To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: ≥50%) or/and mildly reduced EF (HFmrEF: 41-49%) regardless of baseline diabetes. We systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model. We identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p < 0.001, I2 = 0%). When separately analyzed, benefits of SGLT2i remained significant across HFpEF (N = 8891, HR 0.79, 95% CI: 0.71, 0.87, p < 0.001, I2 = 0%) and HFmrEF (N = 4555, HR 0.77, 95% CI: 0.67, 0.89, p < 0.001, I2 = 40%). Consistent benefits were observed also in HFmrEF/HFpEF subgroup without baseline diabetes (N = 6507, HR 0.80, 95% CI: 0.70, 0.91, p < 0.001, I2 = 0%). Sensitivity analysis including the DELIVER and EMPEROR-Preserved trials found a trend towards significant beneficial effects on CV deaths with no heterogeneity (HR 0.90, 95% CI: 0.79, 1.02, p = 0.08, I2 = 0%). This meta-analysis established the place of SGLT2i as a foundational therapy among patients with HF with preserved and mildly reduced EF regardless of diabetes.