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.

Background Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. Methods This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140–180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality. Results Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140–180 mg) and 41.1% (>180 mg/dL), p <.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p <.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31–1.73) (BG 140–180 mg/dL; HR 1.48; 95%CI: 1.29–1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. Conclusions Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.

Context. Calcifediol has been proposed as a potential treatment for COVID-19 patients. Objective: To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized because of COVID-19. Design: Retrospective, multicenter, open, non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D3) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings.

Background Patients with Heart Failure (HF) show impaired functional capacities which have been related to their prognosis. Moreover, physical functional performance in functional tests has also been related to the prognosis in patients with HF. Thus, it would be useful to investigate how physical functional performance in functional tests could determine the prognosis in patients with HF, because HF is the leading cause of hospital admissions for people older than 65 years old. This systematic review and meta-analysis aims to summarise and synthesise the evidence published about the relationship between physical functional performance and prognosis in patients with HF, as well as assess the risk of bias of included studies and the level of evidence per outcome. Methods Major electronic databases, such as PubMed, AMED, CINAHL, EMBASE, PEDro, Web of Science, were searched from inception to March 2020 for observational longitudinal cohort studies (prospective or retrospective) examining the relationship between physical functional performance and prognosis in patients with HF. Results 44 observational longitudinal cohort studies with a total of 22,598 patients with HF were included. 26 included studies reported a low risk of bias, and 17 included studies showed a moderate risk of bias. Patients with poor physical functional performance in the Six Minute Walking Test (6MWT), in the Short Physical Performance Battery (SPPB) and in the Gait Speed Test showed worse prognosis in terms of larger risk of hospitalisation or mortality than patients with good physical functional performance. However, there was a lack of homogeneity regarding which cut-off points should be used to stratify patients with poor physical functional performance from patients with good physical functional performance. Conclusion The review includes a large number of studies which show a strong relationship between physical functional performance and prognosis in patients with HF. Most of the included studies reported a low risk of bias, and GRADE criteria showed a low and a moderate level of evidence per outcome.

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.

Background The effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well known. This work was aimed to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥80 years with type 2 diabetes mellitus (T2DM) hospitalized for COVID-19. Method We conducted a nationwide, multicenter, observational study in patients ≥80 years with T2DM hospitalized for COVID-19 between March 1 and May 29, 2020. The primary outcome measure was in-hospital mortality. A multivariate logistic regression analysis was performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality. Results Of the 2 763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM. Of these patients, 385 (48.7%) died during admission. On the multivariate analysis, the use of dipeptidyl peptidase-4 inhibitors (adjusted odds ratio [AOR] 0.502, 95% confidence interval [CI]: 0.309–0.815, p = .005) and angiotensin receptor blockers (AOR 0.454, 95% CI: 0.274–0.759, p = .003) were independent protectors against in-hospital mortality, whereas the use of acetylsalicylic acid was associated with higher in-hospital mortality (AOR 1.761, 95% CI: 1.092–2.842, p = .020). Other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins showed neutral association with in-hospital mortality. Conclusions We found important differences between cardiometabolic drugs and in-hospital mortality in older patients with T2DM hospitalized for COVID-19. Preadmission treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers could reduce in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins seem to have a neutral effect; and acetylsalicylic acid could be associated with excess mortality.

The use of noninsulin antihyperglycaemic drugs in the hospital setting has not yet been fully described. This observational study compared the efficacy and safety of the standard basal-bolus insulin regimen versus a dipeptidyl peptidase-4 inhibitor (linagliptin) plus basal insulin in medicine department inpatients in real-world clinical practice. We retrospectively enrolled non-critically ill patients with type 2 diabetes with mild to moderate hyperglycaemia and no injectable treatments at home who were treated with a hospital antihyperglycaemic regimen (basal-bolus insulin, or linagliptin-basal insulin) between January 2016 and December 2017. Propensity score was used to match patients in both treatment groups and a comparative analysis was conducted to test the significance of differences between groups. After matched-pair analysis, 227 patients were included per group. No differences were shown between basal-bolus versus linagliptin-basal regimens for the mean daily blood glucose concentration after admission (standardized difference = 0.011), number of blood glucose readings between 100–140 mg/dL (standardized difference = 0.017) and >200 mg/dL (standardized difference = 0.021), or treatment failures (standardized difference = 0.011). Patients on basal-bolus insulin received higher total insulin doses and a higher daily number of injections (standardized differences = 0.298 and 0.301, respectively). Basal and supplemental rapid-acting insulin doses were similar (standardized differences = 0.003 and 0.012, respectively). There were no differences in hospital stay length (standardized difference = 0.003), hypoglycaemic events (standardized difference = 0.018), or hospital complications (standardized difference = 0.010) between groups. This study shows that in real-world clinical practice, the linagliptin-basal insulin regimen was as effective and safe as the standard basal-bolus regimen in non-critical patients with type 2 diabetes with mild to moderate hyperglycaemia treated at home without injectable therapies.

BackgroundParticipation in cardiac rehabilitation (CR) is an essential component of care for patients with coronary artery disease. However, little is known about its benefit on cardiovascular outcomes in patients with diabetes mellitus (DM) who have undergone percutaneous coronary intervention. The aim of our study was to evaluate the impact of CR in this high‐risk group of patients.Methods and ResultsWe performed a retrospective analysis of all patients with DM who underwent percutaneous coronary intervention in Olmsted County (Minnesota) between 1994 and 2010, assessing the impact of CR participation on clinical outcomes. CR participation was significantly lower in patients with DM (38%, 263/700) compared with those who did not have DM (45%, 1071/2379; P=0.004). Using propensity score adjustment, we found that in patients with DM, CR participation was associated with significantly reduced all‐cause mortality (hazard ratio, 0.56; 95% confidence interval, 0.39–0.80; P=0.002) and composite end point of mortality, myocardial infarction, or revascularization (hazard ratio, 0.77; 95% confidence interval, 0.60–0.98; P=0.037), during a median follow‐up of 8.1 years. In patients without DM, CR participation was associated with a significant reduction in all‐cause mortality (hazard ratio, 0.67; 95% confidence interval, 0.55–0.82; P<0.001) and cardiac mortality (hazard ratio, 0.67; 95% confidence interval, 0.47–0.95; P=0.024).Conclusions CR participation after percutaneous coronary intervention is associated with lower all‐cause mortality rates in patients with DM, to a similar degree as for those without DM. However, CR participation was lower in patients with DM, suggesting the need to identify and correct the barriers to CR participation for this higher‐risk group of patients.