Prognosis of acute heart failure in patients followed up in nursing homes in Spain: Results from the RICA registry / Impacto pronóstico en la supervivencia de los pacientes en residencias de ancianos con insuficiencia cardiaca en España: Resultados del Registro RICA

Background: Patients with chronic diseases such as heart failure (HF) are at risk of hospital admission. We evaluated the impact of living in nursing homes (NH) on readmissions and all-cause mortality of HF patients during a one-year follow up. Methods: An observational and multicenter study from the Spanish National Registry of Heart Failure (RICA) was performed. We compared clinical and prognostic characteristics between both groups. Bivariate analyses were performed using Student's t-test and Tukey's method and a Kaplan–Meier survival at one-year follow up. A multivariate proportional hazards analysis of [Cox] regression by the conditional backward method was conducted for the variables being statistically significant related to the probability of death in the univariate. Results: There were 5644 patients included, 462 (8.2%) of whom were nursing home residents. There were 52.7% women and mean age was 79.7±8.8 years. NH residents had lower Barthel (74.07), Charlson (3.27), and Pfeiffer index (2.2), p<0.001). Mean pro-BNP was 6686pg/ml without statistical significance differences between groups. After 1-year follow-up, crude analysis showed no differences in readmissions 74.7% vs. 72.3%, p=0.292, or mortality 63.9% vs. 61.1%, p=0.239 between groups. However, after controlling for confounding variables, NH residents had a higher 1-year all-cause mortality (HR 1.153; 95% CI 1.011–1.317; p=0.034). Kaplan–Meier analysis showed worse survival in nursing home residents (log-rank of 7.12, p=0.008). Conclusions: Nursing home residents with heart failure showed higher one-year mortality which could be due to worse functional status, higher comorbidity, and cognitive deterioration.(AU)

Introducción: Los pacientes con enfermedades crónicas como la insuficiencia cardiaca (IC) presentan mayor riesgo de ingreso. Se evaluó el impacto sobre los reingresos y la mortalidad por todas las causas de los pacientes con IC respecto a vivir o no en residencias de ancianos durante un año de seguimiento. Métodos: Estudio observacional y multicéntrico a partir del Registro Nacional de Insuficiencia Cardiaca (RICA). Se compararon las características clínicas y pronósticas entre ambos grupos. Se realizó un análisis bivariante mediante el método de t de Student y Tukey y un análisis de supervivencia mediante Kaplan-Meier al año de seguimiento, así como un análisis multivariante de riesgos proporcionales de regresión (Cox) por el método de retroceso condicional para las variables que se relacionaban de forma estadísticamente significativa con la probabilidad de muerte en el univariante. Resultados: Fueron incluidos 5.644 pacientes; 462 (8,2%) de ellos estaban en residencias, el 52,7% eran mujeres y la edad media era de 79,7±8,8 años. Los pacientes en residencias tenían menor Barthel (74,07), Charlson (3,27) y Pfeiffer (2,2) (p<0,001). El pro-BNP medio era de 6.686 pg/ml sin diferencias significativas. Tras un año de seguimiento, el análisis bruto no mostró diferencias en los reingresos (74,7 vs. 72,3%; p=0,292) ni en mortalidad (63,9 vs. 61,1%; p=0,239) entre ambos grupos. Tras controlar las variables de confusión, los pacientes en residencias presentaron una mayor mortalidad por todas las causas a un año (hazard ratio 1,153; IC 95%: 1,011-1,317; p=0,034) así como peor supervivencia en el análisis de Kaplan-Meier (log-rank 7,12; p=0,008). Conclusiones: Los pacientes con IC en residencias de ancianos mostraron una mayor mortalidad a un año, que podría deberse a un peor estado funcional, a mayor deterioro cognitivo y a más comorbilidad.(AU)

The two different profiles in heart failure with preserved ejection fraction and type 2 diabetes mellitus: ischemic and diabetic.

OBJECTIVE: Two profiles of patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM) can be discerned: those with ischemic and those with diabetic cardiomyopathy (DMC). We aim to analyze clinical differences and prognosis between patients of these two profiles. MATERIAL AND METHODS: This cohort study analyzes data from the Spanish Heart Failure Registry, a multicenter, prospective registry that enrolled patients admitted for decompensated heart failure and followed them for one year. Three groups were created according to the presence of T2DM and heart disease depending on the etiology (ischemic when coronary artery disease was present, or DMC when no coronary, valvular, or congenital heart disease; no hypertension; nor infiltrative cardiovascular disease observed on an endomyocardial biopsy). The groups and outcomes were compared. RESULTS: A total of 466 patients were analyzed. Group 1 (n = 210) included patients with ischemic etiology and T2DM. Group 2 (n = 112) included patients with DMC etiology and T2DM. Group 3 (n = 144), a control group, included patients with ischemic etiology and without T2DM. Group 1 had more hypertension and dyslipidemia; group 2 had more atrial fibrillation (AF) and higher body mass index; group 3 had more chronic kidney disease and were older. In the regression analysis, group 3 had a better prognosis than group 1 (reference group) for cardiovascular mortality and HF readmissions (HR 0.44;95%CI 0.2-1; p = .049). CONCLUSIONS: Patients with T2DM and HFpEF, who had the poorest prognosis, were of two different profiles: either ischemic or DMC etiology. The first had a higher burden of cardiovascular disease and inflammation whereas the second had a higher prevalence of obesity and AF. The first had a slightly poorer prognosis than the second, though this finding was not significant.

Prognosis of acute heart failure in patients followed up in nursing homes in Spain: Results from the RICA registry.

BACKGROUND: Patients with chronic diseases such as heart failure (HF) are at risk of hospital admission. We evaluated the impact of living in nursing homes (NH) on readmissions and all-cause mortality of HF patients during a one-year follow up. METHODS: An observational and multicenter study from the Spanish National Registry of Heart Failure (RICA) was performed. We compared clinical and prognostic characteristics between both groups. Bivariate analyses were performed using Student's t-test and Tukey's method and a Kaplan-Meier survival at one-year follow up. A multivariate proportional hazards analysis of [Cox] regression by the conditional backward method was conducted for the variables being statistically significant related to the probability of death in the univariate. RESULTS: There were 5644 patients included, 462 (8.2%) of whom were nursing home residents. There were 52.7% women and mean age was 79.7±8.8 years. NH residents had lower Barthel (74.07), Charlson (3.27), and Pfeiffer index (2.2), p<0.001). Mean pro-BNP was 6686pg/ml without statistical significance differences between groups. After 1-year follow-up, crude analysis showed no differences in readmissions 74.7% vs. 72.3%, p=0.292, or mortality 63.9% vs. 61.1%, p=0.239 between groups. However, after controlling for confounding variables, NH residents had a higher 1-year all-cause mortality (HR 1.153; 95% CI 1.011-1.317; p=0.034). Kaplan-Meier analysis showed worse survival in nursing home residents (log-rank of 7.12, p=0.008). CONCLUSIONS: Nursing home residents with heart failure showed higher one-year mortality which could be due to worse functional status, higher comorbidity, and cognitive deterioration.

Prognostic Impact of the UMIPIC Program in the Follow Up in Patients with Heart Failure and Cardiorenal Syndrome.

BACKGROUND: Individuals suffering from heart failure (HF) and cardiorenal syndrome (CRS) represent a special group of patients considering their age, multiple health issues, and treatment challenges. These factors make them more susceptible to frequent hospital stays and a higher mortality rate. UMIPIC is a multidisciplinary care model program for patients with heart failure follow up provided by internists and nurses who are experts in this entity. Our study delved into the effectiveness of this specialized care program (UMIPIC) in mitigating these risks for HF and CRS patients. METHODS: We analyzed the medical records of 3255 patients diagnosed with HF and CRS types 2 and 4, sourced from the RICA registry. These patients were divided into two distinct groups: those enrolled in the UMIPIC program (1205 patients) and those under standard care (2050 patients). Using propensity score matching, we ensured that both groups were comparable. The study focused on tracking hospital admissions and mortality rates for one year after an HF-related hospital stay. RESULTS: Patients in the UMIPIC group experienced fewer hospital readmissions due to HF compared to their counterparts (20% vs. 32%; Hazard Ratio [HR] = 0.48; 95% Confidence Interval [95% CI]: 0.40-0.57; p < 0.001). They also showed a lower mortality rate (24% vs. 36%; HR = 0.64; 95% CI: 0.54-0.75; p < 0.001). Furthermore, the UMIPIC group had fewer total hospital admissions (36% vs. 47%; HR = 0.58; 95% CI: 0.51-0.66; p < 0.001). CONCLUSIONS: The UMIPIC program, centered on holistic and ongoing care, effectively reduces both hospital admissions and mortality rates for HF and CRS patients after a one-year follow-up period.

Glycemic control and prescription profiles in internal medicine inpatients: The role of frailty.

AIM: This work aims to characterize the clinical profile of individuals with frailty syndrome, diabetes mellitus (DM), and hyperglycemia during hospitalization in regard to glycemic control and treatment regimen. METHODS: This cross-sectional multicentric study included patients with DM or hyperglycemia at admission. Demographic data, blood glucose values, treatment administered during hospitalization, and treatment indicated at discharge were analyzed. The sample was divided into three groups according to score on a frailty questionnaire. Generalized additive models were used to describe the relationship between either glycemic variability (GV) or minimum capillary blood glucose and hypoglycemia. Models were adjusted for age, comorbidity, and sarcopenia. RESULTS: A total of 1,137 patients were analyzed. Patients with frailty syndrome had more comorbidity and sarcopenia, worse renal function, and lower albumin and lymphocyte levels. A GV between 21% and 60% was related to a higher probability of hypoglycemia, especially in patients with frailty. Regarding minimum capillary blood glucose, patients with frailty had the highest probability of hypoglycemia. This probability remained significant even in the group with frailty in which, with a reference value of 200 mg/dl, the adjusted odds ratio of a minimum capillary blood glucose of 151 mg/dL was 1.08 (95% confidence interval (1.12-1.05)). Baseline treatments showed a significant predominance of insulin use in the frailest groups. CONCLUSIONS: Patients with frailty had more sarcopenia and undernourishment. These patients were managed in a similar manner during hospitalization to patients without frailty, despite their higher risk of hypoglycemia according to GV or minimum capillary blood glucose levels.

Approach to obesity in the elderly population: a consensus report from the Diabetes, Obesity and Nutrition Working Group of SEMI (Spanish Society of Internal Medicine).

Obesity in the elderly not only impacts morbidity and mortality but their quality of life. This phenomenon has sparked extensive research and debate regarding treatment recommendations, primarly due to the lack evidence in this specific population. When addressing possible treatment recommendations for older adults with obesity, it is crucial to assess certain essential aspects such as functional status, sarcopenia, cognitive status, and others. Intentional weight loss in this population can be both effective and safe. The best weight loss plan for the elderly revolves around adopting a healthy lifestyle, which includes following a Mediterranean diet pattern and engaging in physical exercise, particularly strength training. Additionally, the use of weight loss medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RA) and novel glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, can provide an additional stage of treatment. In selective candidates, bariatric surgery may also be considered. The objective of this document is to propose a comprehensive algorithm of recommendations for the management of obesity in the elderly (above the age of 65), based on scientific evidence and the expertise of members from the Diabetes, Obesity, and Nutrition Workgroup of the Spanish Society of Internal Medicine.

Projected effectiveness of dapagliflozin in heart failure with reduced ejection fraction in clinical practice.

Aim: To estimate the projected effectiveness of dapagliflozin in subjects with heart failure (HF) with reduced ejection fraction in clinical practice in Spain. Materials & methods: This multicenter cohort study included subjects aged 50 years or older consecutively hospitalized for HF in internal medicine departments in Spain. The projected clinical benefits of dapagliflozin were estimated based on results from the DAPA-HF trial. Results: A total of 1595 patients were enrolled, of whom 1199 (75.2%) were eligible for dapagliflozin. Within 1 year after discharge, 21.6% of patients eligible for dapagliflozin were rehospitalized for HF and 20.5% died. Full implementation of dapagliflozin led to an absolute risk reduction of 3.5% for mortality (number needed to treat = 28) and 6.5% (number needed to treat = 15) for HF readmission. Conclusion: Treatment with dapagliflozin in clinical practice may markedly reduce mortality and readmissions for HF.

Heart failure with reduced ejection fraction is a severe disease with a high risk of hospitalization and mortality. With this condition, the heart muscle cannot pump properly. This means that not enough blood is pumped from the heart, reducing the amount of oxygen to the body. Fortunately, there are treatments that reduce this risk, in patients with heart failure. SGLT2 inhibitors, including dapagliflozin, are among the first therapies given to patients with heart failure. In this study, we investigated the potential benefits of adding dapagliflozin to the treatment of patients admitted to the hospital in Spain for heart failure with reduced ejection fraction. Our data showed that dapagliflozin was able to reduce the risk of further events (e.g., heart attack) in these patients.

Improving prediction of COVID-19 mortality using machine learning in the Spanish SEMI-COVID-19 registry.

COVID-19 is responsible for high mortality, but robust machine learning-based predictors of mortality are lacking. To generate a model for predicting mortality in patients hospitalized with COVID-19 using Gradient Boosting Decision Trees (GBDT). The Spanish SEMI-COVID-19 registry includes 24,514 pseudo-anonymized cases of patients hospitalized with COVID-19 from 1 February 2020 to 5 December 2021. This registry was used as a GBDT machine learning model, employing the CatBoost and BorutaShap classifier to select the most relevant indicators and generate a mortality prediction model by risk level, ranging from 0 to 1. The model was validated by separating patients according to admission date, using the period 1 February to 31 December 2020 (first and second waves, pre-vaccination period) for training, and 1 January to 30 November 2021 (vaccination period) for the test group. An ensemble of ten models with different random seeds was constructed, separating 80% of the patients for training and 20% from the end of the training period for cross-validation. The area under the receiver operating characteristics curve (AUC) was used as a performance metric. Clinical and laboratory data from 23,983 patients were analyzed. CatBoost mortality prediction models achieved an AUC performance of 84.76 (standard deviation 0.45) for patients in the test group (potentially vaccinated patients not included in model training) using 16 features. The performance of the 16-parameter GBDT model for predicting COVID-19 hospital mortality, although requiring a relatively large number of predictors, shows a high predictive capacity.

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity.

AIM: This work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments. METHODS: This study analyzed patients in an ongoing, multicenter, prospective, pre-post, uncontrolled cohort registry that enrolls unique, consecutive patients with type 2 diabetes treated with weekly subcutaneous semaglutide. Steatosis/fibrosis were determined by HSI (<30 ruled out, >36 steatosis) and FIB-4 (<1.3 ruled out, >2.67 fibrosis), respectively. RESULTS: The sample included 213 patients (46.9% women) with a median age of 64 (19) years. The median baseline body mass index and weight were 36.1 (8.4) kg/m2 and 98 (26.9) kg, respectively. A total of 99.9% had HSI values indicating steatosis, with a mean HSI of 47.9 (8.2). Additionally, 10.8% had fibrosis (FIB-4 > 2.67) and 42.72% had values in intermediate ranges (FIB-4 1.3-2.67). At 24 weeks, there was a significant reduction in HSI (-2.36 (95%CI 1.83-2.9) p < 0.00001) and FIB-4 (-0.075 (95%CI 0.015-0.14) p < 0.016), mainly related to declines in body weight, triglyceride levels, insulin resistance (estimated by the triglyceride-glucose index), and liver enzymes. CONCLUSION: These results show that weekly subcutaneous semaglutide had a beneficial effect on liver steatosis that went beyond glucose control. Its effects were mainly related to weight loss, a decline in biomarkers, and improvements in insulin sensitivity. For many patients, early detection is essential for improving MAFLD outcomes and may allow for selecting the most efficient treatment options.

Beta-blocker use in patients with heart failure with preserved ejection fraction and sinus rhythm.

INTRODUCTION: Beta-adrenergic receptor blockers (beta-blockers) are frequently used for patients with heart failure (HF) with preserved ejection fraction (HFpEF), although evidence-based recommendations for this indication are still lacking. Our goal was to assess which clinical factors are associated with the prescription of beta-blockers in patients discharged after an episode of HFpEF decompensation, and the clinical outcomes of these patients. METHODS: We assessed 1078 patients with HFpEF and in sinus rhythm who had experienced an acute HF episode to explore whether prescription of beta-blockers on discharge was associated with one-year all-cause mortality or the composite endpoint of one-year all-cause death or HF readmission. We also examined the clinical factors associated with beta-blocker discharge prescription for such patients. RESULTS: At discharge, 531 (49.3%) patients were on beta-blocker therapy. Patients on beta-blockers more often had a prior diagnosis of hypertension and more comorbidity (including ischemic heart disease) and a better functional status, but less often a prior diagnosis of chronic obstructive pulmonary disease. These patients had a lower heart rate on admission and more often used angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and loop diuretics. One year after the index admission, 161 patients (15%) had died and 314 (29%) had experienced the composite endpoint. After multivariate adjustment, beta-blocker prescription was not associated with either all-cause mortality (HR=0.83 [95% CI 0.61-1.13]; p=0.236) or the composite endpoint (HR=0.98 [95% CI 0.79-1.23]; p=0.882). CONCLUSION: In patients with HFpEF in sinus rhythm, beta-blocker use was not related to one-year mortality or mortality plus HF readmission.

High-Risk Obesity Phenotypes: Target for Multimorbidity Prevention at the ROFEMI Study.

Background: Describe the profile of patients with obesity in internal medicine to determine the role of adiposity and related inflammation on the metabolic risk profile and, identify various "high-risk obesity" phenotypes by means of a cluster analysis. This study aimed to identify different profiles of patients with high-risk obesity based on a cluster analysis. Methods: Cross-sectional, multicenter project that included outpatients attended to in internal medicine. A total of 536 patients were studied. The mean age was 62 years, 51% were women. Patients were recruited from internal medicine departments over two weeks in November and December 2021 and classified into four risk groups according to body mass index (BMI) and waist circumference (WC). High-risk obesity was defined as BMI > 35 Kg/m2 or BMI 30−34.9 Kg/m2 and a high WC (>102 cm for men and >88 cm for women). Hierarchical and partitioning clustering approaches were performed to identify profiles. Results: A total of 462 (86%) subjects were classified into the high-risk obesity group. After excluding 19 patients missing critical data, two profiles emerged: cluster 1 (n = 396) and cluster 2 (n = 47). Compared to cluster 1, cluster 2 had a worse profile, characterized by older age (77 ± 16 vs. 61 ± 21 years, p < 0.01), a Charlson Comorbidity Index > 3 (53% vs. 5%, p < 0.001), depression (36% vs. 19%, p = 0.008), severe disability (64% vs. 3%, p < 0.001), and a sarcopenia score ≥ 4 (79% vs. 16%, p < 0.01). In addition, cluster 2 had greater inflammation than cluster 1 (hsCRP: 5.8 ± 4.1 vs. 2.1 ± 4.5 mg/dL, p = 0.008). Conclusions: Two profiles of subjects with high-risk obesity were identified. Based on that, older subjects with obesity require measures that target sarcopenia, disability, psychological health, and significant comorbidities to prevent further health deterioration. Longitudinal studies should be performed to identify potential risk factors of subjects who progress from cluster 1 to cluster 2.

The Effects of a Therapeutic Strategy Guided by Lung Ultrasound on 6-Month Outcomes in Patients with Heart Failure: Results from the EPICC Randomized Controlled Trial.

Background: Pulmonary congestion (PC) is associated with an increased risk of hospitalization and death in patients with heart failure (HF). Lung ultrasound is highly sensitive for detecting PC. The aim of this study is to evaluate whether lung ultrasound-guided therapy improves 6-month outcomes in patients with HF. Methods: A randomized, multicenter, single-blind clinical trial in patients discharged after hospitalization for decompensated HF. Participants were assigned 1:1 to receive treatment guided according to the presence of lung ultrasound signs of congestion (semi-quantitative evaluation of B lines and the presence of pleural effusion) versus standard of care (SOC). The primary endpoint was the combination of cardiovascular death, readmission, or emergency department or day hospital visit due to worsening HF at 6 months. In September 2020, after an interim analysis, patient recruitment was stopped. Results: A total of 79 patients were randomized (mean age 81.2 +/− 9 years) and 41 patients (51.8%) showed a left ventricular ejection fraction >50%. The primary endpoint occurred in 11 patients (29.7%) in the SOC group and in 11 patients (26.1%) in the LUS group (log-rank = 0.83). Regarding nonserious adverse events, no significant differences were found. Conclusions: LUS-guided diuretic therapy after hospital discharge due to ADHF did not show any benefit in survival or a need for intravenous diuretics compared with SOC.

Prognostic Significance of the PROFUND Index on One Year Mortality in Acute Heart Failure: Results from the RICA Registry.

Background: Heart failure (HF) is a syndrome with high prevalence, mainly affecting elderly patients, where the presence of associated comorbidities is of great importance. Methods: An observational study from a prospective registry was conducted. Patients identified from the National Registry of Heart Failure (RICA), which belongs to the Working Group on Heart Failure and Atrial Fibrillation of the Spanish Society of Internal Medicine (SEMI), were included. The latter is a prospective, multicenter registry that has been active since 2008. It includes individual consecutive patients over 50 years of age with a diagnosis of HF at hospital discharge (acute decompensated or new-onset HF). Results: In total, 5424 patients were identified from the registry. Forty-seven percent were men and mean left ventricular ejection fraction (LVEF) was 51.4%; 1132 had a score of 0 to 2 according to the PROFUND index, 3087 had a score of 3 to 6, and 952 patients had a score of 7 to 10 points. In the sample, 252 patients had a score above 11 points. At the end of the year of follow-up, 61% of the patients died. This mortality increased proportionally as the PROFUND index increased, specifically 75% for patients with PROFUND greater than 11. The Kaplan-Meier survival curve shows that survival at one year progressively decreases as the PROFUND index value increases. Thus, subjects with scores greater than seven (intermediate-high and high-risk) presented the worst survival with a log rank of 0.96 and a p < 0.05. In the regression analysis, we found a higher risk of death from any cause at one year in the group with the highest risk according to the PROFUND index (score greater than 11 points (HR 1.838 (1.410−2.396)). Conclusions: The PROFUND index is a good index for predicting mortality in patients admitted for acute HF, especially in those subjects at intermediate to high risk with scores above seven. Future studies should seek to determine whether the PROFUND index score is simply a prognostic marker or whether it can also be used to make therapeutic decisions for those subjects with very high short-term mortality.

The importance of association of comorbidities on COVID-19 outcomes: a machine learning approach.

BACKGROUND: The individual influence of a variety of comorbidities on COVID-19 patient outcomes has already been analyzed in previous works in an isolated way. We aim to determine if different associations of diseases influence the outcomes of inpatients with COVID-19. METHODS: Retrospective cohort multicenter study based on clinical practice. Data were taken from the SEMI-COVID-19 Registry, which includes most consecutive patients with confirmed COVID-19 hospitalized and discharged in Spain. Two machine learning algorithms were applied in order to classify comorbidities and patients (Random Forest -RF algorithm, and Gaussian mixed model by clustering -GMM-). The primary endpoint was a composite of either, all-cause death or intensive care unit admission during the period of hospitalization. The sample was randomly divided into training and test sets to determine the most important comorbidities related to the primary endpoint, grow several clusters with these comorbidities based on discriminant analysis and GMM, and compare these clusters. RESULTS: A total of 16,455 inpatients (57.4% women and 42.6% men) were analyzed. According to the RF algorithm, the most important comorbidities were heart failure/atrial fibrillation (HF/AF), vascular diseases, and neurodegenerative diseases. There were six clusters: three included patients who met the primary endpoint (clusters 4, 5, and 6) and three included patients who did not (clusters 1, 2, and 3). Patients with HF/AF, vascular diseases, and neurodegenerative diseases were distributed among clusters 3, 4 and 5. Patients in cluster 5 also had kidney, liver, and acid peptic diseases as well as a chronic obstructive pulmonary disease; it was the cluster with the worst prognosis. CONCLUSION: The interplay of several comorbidities may affect the outcome and complications of inpatients with COVID-19.

Effect of newer antihyperglycemic drugs on liver steatosis indices in patients with diabetes and obesity.

AIM: To assess the efficacy of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptors agonist (GLP-1RA) therapy on liver steatosis measured by fatty liver index (FLI) and hepatic steatosis index (HSI) at 26 weeks in outpatients with diabetes and obesity. METHODS: Observational, prospective, multicenter study. Patients with steatosis determined by FLI (values <30 rule out and >60 indicate steatosis) and HIS (values <30 rule out and >36 indicate steatosis) who received combination therapy were included. Patients were stratified into three groups according to the sequential order of treatment. We used robust statistical methods. RESULTS: In our final report we included 174 patients (58.6% males), mean age 61.9 (10) years. Baseline body mass index, waist circumference and weight were 36.5 (6.8) kg/m2, 117.5 (15.1) cm and 99.4 (20.5) kg, respectively. One hundred percent of patients had altered biomarkers of fatty liver scores (FLI 96 [13] and HSI 49.2 [8.5]). At 26 weeks, significant reductions in FLI (-4.5 [95% CI 3.5-5.9] p < .001) and HSI (-2.4 [95% CI 1.6-3.2] p < .001) were found in the total sample and pre-specified treatment and FLI cut-off point subgroups. CONCLUSION: Our results show a beneficial effect of the combination of GLP-1RAs plus SGLT2is on liver steatosis that goes beyond glucose control, and it is related mainly to weight loss, a decline in biomarkers and reductions in abdominal circumference. For many patients, early detection is essential to improving outcomes in NAFLD and could allow us to select the most efficient treatment options.