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Effect of newer antihyperglycemic drugs on liver steatosis indices in patients with diabetes and obesity.
Carretero Gómez, J, Ena, J, Seguí Ripoll, JM, Carrasco-Sánchez, FJ, Gómez Huelgas, R, Casas Rojo, JM, Suárez Tembra, M, Carabantes Rueda, JJ, Arévalo Lorido, JC
Current medical research and opinion. 2021;(11):1867-1873
Abstract
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.
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Prior Treatment with Statins is Associated with Improved Outcomes of Patients with COVID-19: Data from the SEMI-COVID-19 Registry.
Torres-Peña, JD, Pérez-Belmonte, LM, Fuentes-Jiménez, F, López Carmona, MD, Pérez-Martinez, P, López-Miranda, J, Carrasco Sánchez, FJ, Vargas Núñez, JA, Del Corral Beamonte, E, Magallanes Gamboa, JO, et al
Drugs. 2021;(6):685-695
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Abstract
BACKGROUND The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.
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Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study.
Pérez-Belmonte, LM, Torres-Peña, JD, López-Carmona, MD, Ayala-Gutiérrez, MM, Fuentes-Jiménez, F, Jorge Huerta, L, Muñoz, JA, Rubio-Rivas, M, Madrazo, M, Garcia, MG, et al
BMC medicine. 2020;(1):359
Abstract
BACKGROUND Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.
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Efficacy and safety of insulin glargine 300 U/mL (Gla-300) during hospitalization and therapy intensification at discharge in patients with insufficiently controlled type 2 diabetes: results of the phase IV COBALTA trial.
Perez, A, Carrasco-Sánchez, FJ, González, C, Seguí-Ripoll, JM, Trescolí, C, Ena, J, Borrell, M, Gomez Huelgas, R
BMJ open diabetes research & care. 2020;(1)
Abstract
INTRODUCTION This study assessed the efficacy and safety of insulin glargine 300 U/mL (Gla-300) during hospitalization and therapy intensification at discharge in insufficiently controlled people with type 2 diabetes. RESEARCH DESIGN AND METHODS COBALTA (for its acronym in Spanish, COntrol Basal durante la hospitalizacion y al ALTA) was a multicenter, open-label, single-arm, phase IV trial including 112 evaluable inpatients with type 2 diabetes insufficiently controlled (glycosylated hemoglobin (HbA1c) 8%-10%) with basal insulin and/or non-insulin antidiabetic drugs. Patients were treated with a basal-bolus-correction insulin regimen with Gla-300 during the hospitalization and with Gla-300 and/or non-insulin antidiabetics for 6 months after discharge. The primary endpoint was the HbA1c change from baseline to month 6 postdischarge. RESULTS HbA1c levels decreased from 8.8%±0.6% at baseline to 7.2%±1.1% at month 6 postdischarge (p<0.001, mean change 1.6%±1.1%). All 7-point blood glucose levels decreased from baseline to 24 hours predischarge (p≤0.001, mean changes from 25.1±66.6 to 63.0±85.4 mg/dL). Fasting plasma glucose also decreased from baseline to 24 hours predischarge (p<0.001), month 3 (p<0.001) and month 6 (p<0.001) postdischarge (mean changes 51.5±90.9, 68.2±96.0 and 77.6±86.4 mg/dL, respectively). Satisfaction was high and hyperglycemia/hypoglycemia perception was low according to the Diabetes Treatment Satisfaction Questionnaire at month 6 postdischarge. The incidence of confirmed (glucose<70 mg/dL)/severe hypoglycemia was 25.0% during hospitalization and 59.1% 6 months after discharge. No safety concerns were reported. CONCLUSIONS Inpatient and intensification therapy at discharge with Gla-300 improved significantly glycemic control of patients with type 2 diabetes insufficiently controlled with other basal insulin and/or non-insulin antidiabetic medication, with high treatment satisfaction. Gla-300 could therefore be a treatment choice for hospital and postdischarge diabetes management.
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Combination Therapy With Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients With Type 2 Diabetes: A Real-World Evidence Study.
Carretero Gómez, J, Arévalo Lorido, JC, Gómez Huelgas, R, García de Lucas, D, Mateos Polo, L, Varela Aguilar, JM, Seguí Ripoll, JM, Ena, J, ,
Canadian journal of diabetes. 2019;(3):186-192
Abstract
OBJECTIVES Scientific literature about the combination of glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients is scarce. We sought to assess the real-world efficacy and safety of SGLT2 inhibitors and GLP-1ra combination therapy in older patients (>65 years of age). METHODS This was an observational, prospective, multicenter study based on clinical practice. Patients were stratified according to tertiles of baseline glycated hemoglobin (A1C) levels and to treatment schedule. RESULTS We included 113 patients (65.5% men, mean age 70.4±8.8 years). The body mass index was 36.5 (±6.6) kg/m2. The baseline A1C level was 8.0% (±1.2%). At the 6-month follow up, we found a significant reduction in A1C levels (-1.1%; p<0.0001), body mass index (-2.1 kg/m2; p<0.00003) and systolic blood pressure (-13 mmHg; p<0.000005). Patients who had the highest baseline A1C levels (≥8.4%) showed greater improvement in A1C levels (p<0.0001), weight (p<0.0001) and quality-of-life scores (p<0.0001). The greatest reduction in A1C levels and weight was seen in patients who started both drugs simultaneously (p<0.0001). The second greatest reduction was seen when GLP-1ra was added to previous treatment with an SGLT2i (p<0.0001). Also of note was a decrease in systolic blood pressure in patients for whom an SGLT2i was added to previous GLP-1ra treatment (p<0.0001). Of the patients, 34.3% achieved the combined endpoint of A1C levels <7% and weight loss ≥5% without hypoglycemia. CONCLUSIONS This study's findings provide evidence of clinically meaningful reductions in A1C level, body weight and systolic blood pressure in older patients with type 2 diabetes who are taking combined regimens. The dropout and hypoglycemia rates were minimal, and treatment was tolerated well.
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Switching from suppressive protease inhibitor-based regimens to nevirapine-based regimens: a meta-analysis of randomized controlled trials.
Ena, J, Leach, A, Nguyen, P
HIV medicine. 2008;(9):747-56
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Abstract
OBJECTIVES We performed a meta-analysis to assess the efficacy and safety of switching from protease inhibitor (PI)- to nevirapine (NVP)-based regimens in HIV-infected patients in whom virological suppression had been achieved. METHODS Six trials (550 patients) were analysed. The demographics showed that 11-48% of participants were female and 40-53% had hepatitis C or B virus infection, and the mean CD4 lymphocyte count was >500 cells/microL at study entry. RESULTS NVP-based regimens showed noninferiority compared with continuation of PI therapy to maintain virological suppression in 'intention to treat' (80 vs. 78%; P=0.35) and 'on treatment' analyses (91 vs. 89%; P=0.10). Overall rates of discontinuation because of adverse events were similar in the two groups (11 vs. 10%; P=0.79). However, NVP-based therapies caused more discontinuations because of liver toxicity than PI-based therapies (7 vs. 0%; P=0.0009). At the end of follow-up there was no statistical difference in CD4, cholesterol, triglyceride and body shape measurements between the two groups. Two studies reported greater improvement in quality of life in patients who were switched to the NVP group. CONCLUSIONS Switching from suppressive PI- to NVP-based regimens is virologically and immunologically safe; however, the risk of liver toxicity requires monitoring of clinical symptoms and liver chemistry during NVP therapy.
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Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: a meta-analysis.
Letelier, LM, Udol, K, Ena, J, Weaver, B, Guyatt, GH
Archives of internal medicine. 2003;(7):777-85
Abstract
BACKGROUND Although clinicians sometimes choose amiodarone to convert atrial fibrillation (AF) to sinus rhythm, no current and comprehensive systematic review has summarized its effectiveness. OBJECTIVE To review the effectiveness of amiodarone in converting AF to sinus rhythm over a 4-week period. METHODS Two reviewers conducted a systematic search for randomized trials in databases, complemented by hand searches and contact with experts. Selected trials compared amiodarone with placebo, digoxin, or calcium channel blockers for conversion of AF to sinus rhythm. Reviewers evaluated the methodology and extracted data from each primary study. RESULTS Twenty-one studies met eligibility criteria. Duration of AF proved to be a source of heterogeneity, leading to 2 analyses. The relative risk (RR) for achieving sinus rhythm was 4.33 (95% confidence interval [CI], 2.76-6.77) for trials with mean AF duration of greater than 48 hours and 1.40 (95% CI, 1.25-1.57) for those with AF of 48 hours or less. The risk differences for these 2 groups were 27% and 26%, respectively, yielding a number needed to treat of 4 for both groups. The low control event rate among trials with long duration of AF, compared with that of trials with a duration of 48 hours or less, explained the difference in the RR for conversion. We found that the size of the left atrium, presence of cardiovascular disease, and protocols of amiodarone administration did not influence the magnitude of effect. Serious adverse events were infrequent. CONCLUSIONS Amiodarone is effective for converting AF to sinus rhythm in a wide range of patients. Although use of amiodarone is apparently safe, safety data are too scarce for definitive conclusions.
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Usefulness of basal and pilocarpine-stimulated salivary flow in primary Sjögren's syndrome. Correlation with clinical, immunological and histological features.
Rosas, J, Ramos-Casals, M, Ena, J, García-Carrasco, M, Verdu, J, Cervera, R, Font, J, Caballero, O, Ingelmo, M, Pascual, E
Rheumatology (Oxford, England). 2002;(6):670-5
Abstract
OBJECTIVES To examine salivary function in patients with primary Sjögren's syndrome (SS) by assessing unstimulated and stimulated flows using 5 mg of pilocarpine in a 5% solution, in order to define their clinical usefulness in the evaluation of xerostomia in patients with primary SS as well as to identify those factors related to the increase in salivary flow after pilocarpine stimulation. METHODS We investigated the clinical and immunological characteristics of 60 consecutive patients with primary SS. All patients fulfilled four or more of the preliminary diagnostic European criteria for SS. We measured unstimulated (basal) salivary flow (BSF) in all patients. In patients with BSF ≤1.5 ml, stimulated salivary flows (SSF) were also measured after stimulation with an ophthalmic 5% pilocarpine solution (0.1 ml=5 mg, administered sublingually). SSF was also measured after oral administration of 50 mg anetholetrithione (ANTT) in the same patients. These stimulated salivary flows were measured 1, 2 and 3 h after the stimulus. RESULTS Of the 60 patients, 55 were women and five men, with a mean age at the SS onset of 61 yr (range 18-82 yr). The mean BSF for SS patients was 1.40+/-0.17 ml. Fifty (83%) patients showed a BSF less than 1.5 ml. The stimulated salivary flow after 1 h was 3.23 ml in the pilocarpine group and 0.57 in the ANTT group (P<0.001); after 2 h it was 1.32 ml in the pilocarpine group and 0.52 in the ANTT group (P=0.02) and after 3 h it was 0.80 ml in the pilocarpine group and 0.41 in the ANTT group (P=0.046). No clinical or immunological differences were found between SS patients with BSF more or less than 1.5 ml, although patients with a BSF less than 1.5 ml showed a parotid scintigraphy class III or IV more frequently (42 vs 0%, P=0.01). SS patients with a pilocarpine SSF less than 1.5 ml had a longer duration of SS (73.3 vs 31.3 months, P=0.03) and a higher prevalence of positive anti-Ro/SS-A (70 vs 36%, P=0.038), anti-La/SS-B (65 vs 32%, P=0.038), parotid scintigraphy class III-IV (79 vs 9%, P<0.001) and positive salivary gland biopsy (90 vs 43%, P<0.001). CONCLUSION The study of xerostomia using basal and pilocarpine SSF is simple to perform, acceptable to patients and needs no special equipment. We describe a significant increase in SSF using a solution of 5% pilocarpine in comparison with salivary flow obtained after stimulation with ANTT. Twenty-two of the 46 patients with low BSF had stimulated flows over 1.5 ml. These 'responder' patients showed a shorter duration of sicca symptoms, a lower frequency of positive immunological markers and milder grades of scintigraphic patterns and lymphocytic infiltrates in salivary gland biopsies. This subset of patients probably maintain a residual capacity of their salivary glands, as opposed to the 'non-responder' patients, who had a longer duration of sicca syndrome evolution with more severe involvement of the salivary glands.