Management of older hospitalized patients with type 2 diabetes using linagliptin: Lina-Older study.

BACKGROUND: Older patients managed with intensive antidiabetic therapy are more likely to be harmed. Our study's primary endpoint was to analyze the safety and efficacy of linagliptin in combination with basal insulin versus basal-bolus insulin in patients with 75 years of age or older hospitalized in medicine and surgery departments in real-world clinical practice. METHODS: We retrospectively enrolled non-critically patients ≥75 years with type 2 diabetes admitted to medicine and non-cardiac surgery departments with admission glycated hemoglobin <8%, admission blood glucose <240 mg/dL, and without at-home injectable therapies managed with our hospital's antihyperglycemic protocol (basal-bolus or linagliptin-basal regimens) between January 2016 and December 2018. To match each patient who started on the basal-bolus regimen with a patient who started on the linagliptin-basal regimen, a propensity matching analysis was used. RESULTS: Postmatching, 198 patients were included in each group. There were no significant differences in mean daily blood glucose levels after admission (P=0.203); patients with mean blood glucose 100-140mg/dL (P=0.134), 140-180mg/dL (P=0.109), or >200mg/dL (P=0.299); and number and day of treatment failure (P=0.159 and P=0.175, respectively). The total insulin dose and the number of daily injections were significantly lower in the linagliptin-basal group (both, P<0.001). Patients on the basal-bolus insulin regimen had more total hypoglycemic events than patients on the linagliptin-basal insulin regimen (P<0.001). CONCLUSIONS: The linagliptin-basal insulin regimen was an effective alternative with fewer hypoglycemic events and daily insulin injections than intensive basal-bolus insulin in very old patients with type 2 diabetes with mild-to-moderate hyperglycemia treated at home without injectable therapies.

Clinical benefits of empagliflozin in very old patients with type 2 diabetes hospitalized for acute heart failure.

BACKGROUND: There is little evidence on the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients with heart failure. This work analyzed the clinical efficacy and safety of empagliflozin continuation in very old patients with type 2 diabetes hospitalized for acute decompensated heart failure. METHODS: We conducted a real-world observational study between September 2015 and June 2021. Patients ≥80 years were grouped by antihyperglycemic regimen: (1) continuation of preadmission empagliflozin combined with basal insulin regimen and (2) conventional basal-bolus insulin regimen. A propensity score matching analysis matched patients in both groups in a 1:1 manner. The primary outcome was differences in clinical efficacy measured by the visual analogue scale dyspnea score, NT-proBNP levels, diuretic response, and cumulative urine output. Safety endpoints such as adverse events, worsening heart failure, discontinuation of empagliflozin, length of hospital stay, and in-hospital deaths were also analyzed. RESULTS: After propensity score matching, 79 patients were included in each group. At discharge, the N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were lower in the empagliflozin continuation group than in the insulin group (1699 ± 522 vs. 2303 ± 598 pg/ml, p = 0.021). Both the diuretic response and cumulative urine output were greater in patients treated with empagliflozin than in patients with basal-bolus insulin during the hospitalization (at discharge: -0.14 ± -0.06 vs. -0.24 ± -0.10, p = 0.044; and 16,100 ± 1510 vs. 13,900 ± 1220 ml, p = 0.037, respectively). No differences were observed in safety outcomes. CONCLUSIONS: In very old patients with type 2 diabetes hospitalized for acute heart failure, continuing preadmission empagliflozin reduced NT-proBNP levels and increased diuretic response and urine output compared to a basal-bolus insulin regimen. The empagliflozin regimen also showed a good safety profile.

Statins and Peripheral Arterial Disease: A Narrative Review.

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic condition. In patients with PAD, the presence of intermittent claudication leads to a deterioration in quality of life. In addition, even in asymptomatic cases, patients with PAD are at high risk of cardiac or cerebrovascular events. Treatment of PAD is based on lifestyle modifications; regular exercise; smoking cessation; and control of cardiovascular risk factors, including hypercholesterolemia. A growing number of studies have shown that statins reduce cardiovascular risk and improve symptoms associated with PAD. Current guidelines recommend the use of statins in all patients with PAD in order to decrease cardiovascular events and mortality. However, the prescribing of statins in patients with PAD is lower than in those with coronary heart disease. This review provides relevant information from the literature that supports the use of statins in patients with PAD and shows their potential benefit in decreasing lower limb complications as well as cardiovascular morbidity and mortality.

Efficacy and Safety of Empagliflozin Continuation in Patients with Type 2 Diabetes Hospitalised for Acute Decompensated Heart Failure.

There is little evidence on the use of sodium-glucose cotransporter 2 inhibitors in hospitalised patients. This work aims to analyse the glycaemic and clinical efficacy and safety of empagliflozin continuation in patients with type 2 diabetes hospitalised for acute decompensated heart failure. This real-world observational study includes patients treated using our in-hospital antihyperglycaemic regimens (basal-bolus insulin vs. empagliflozin-basal insulin) between 2017 and 2020. A propensity matching analysis was used to match a patient on one regimen with a patient on the other regimen. Our primary endpoints were the differences in glycaemic control, as measured via mean daily blood glucose levels, and differences in the visual analogue scale dyspnoea score, NT-proBNP levels, diuretic response, and cumulative urine output. Safety endpoints were also analysed. After a propensity matching analysis, 91 patients were included in each group. There were no differences in mean blood glucose levels (152.1 ± 17.8 vs. 155.2 ± 19.7 mg/dL, p = 0.289). At discharge, NT-proBNP levels were lower and cumulative urine output greater in the empagliflozin group versus the basal-bolus insulin group (1652 ± 501 vs. 2101 ± 522 pg/mL, p = 0.032 and 16,100 ± 1510 vs. 13,900 ± 1220 mL, p = 0.037, respectively). Patients who continued empagliflozin had a lower total number of hypoglycaemic episodes (36 vs. 64, p < 0.001). No differences were observed in adverse events, length of hospital stay, or in-hospital deaths. For patients with acute heart failure, an in-hospital antihyperglycaemic regimen that includes continuation of empagliflozin achieved effective glycaemic control, lower NT-proBNP, and greater urine output. It was also safer, as it reduced hypoglycaemic episodes without increasing other safety endpoints.

Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study.

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.

De-Intensification of Antidiabetic Treatment Using Canagliflozin in Patients with Heart Failure and Type 2 Diabetes: Cana-Switch-HF Study.

Canagliflozin is a sodium-glucose co-transporter 2 inhibitor that reduces glycemia as well as the risk of cardiovascular events. Our main objective was to analyze antidiabetic treatment de-intensification and the glycemic efficacy of replacing antidiabetic agents (excluding metformin) with canagliflozin in patients with heart failure and type 2 diabetes with poor glycemic control. In this observational, retrospective, real-world study, we selected patients treated with metformin in combination with ≥2 non-insulin antidiabetic agents or metformin in combination with basal insulin plus ≥1 non-insulin antidiabetic agent. Non-insulin antidiabetic agents were replaced with canagliflozin. Patients were followed-up on at three, six, and 12 months after the switch and a wide range of clinical variables were recorded. A total of 121 patients were included. From baseline to 12 months, the number of antidiabetic agents (3.1 ± 1.0 vs. 2.1 ± 0.8, p < 0.05), basal insulin dose (20.1 ± 9.8 vs. 10.1 ± 6.5 units, p < 0.01), and percentage of patients who used basal insulin (47.9% vs. 31.3%, p < 0.01) decreased. The proportion of patients who used diuretics also declined significantly. In addition, we observed improvement in glycemic control, with an increase in the proportion of patients with glycated hemoglobin <7% from 16.8% at three months to 63.5% at 12 (p < 0.001). Canagliflozin use was also beneficial in terms of body weight, blood pressure, heart failure status, functional class, and cardiovascular-renal risk. There were also reductions in the number of emergency department visits and hospitalizations for heart failure. Moreover, canagliflozin was well-tolerated, with a low rate of drug-related discontinuation. Mounting evidence from randomized controlled trials and real-world studies point to the beneficial profile of sodium-glucose co-transporter type 2 inhibitors such as canagliflozin in patients with heart failure.

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.

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.

Differences between Clinical Protocols for the Treatment of Coronavirus Disease 2019 (COVID-19) in Andalusia, Spain.

Our objective was to compare clinical protocols for the treatment of the novel coronavirus disease 2019 (COVID-19) among different hospitals in Andalusia, Spain. We reviewed the current COVID-19 protocols of the 15 largest hospitals in Andalusia. Antiviral treatment, empirical antibacterial agents, adjunctive therapies, anticoagulant treatment, supportive care, hospital organization, and discharge recommendations were analyzed. All protocols included were the latest updates as of July 2020. Hydroxychloroquine in monotherapy was the most frequent antiviral drug recommended for mild respiratory illness with clinical risk factors (33.3%). Combined hydroxychloroquine with azithromycin or lopinavir/ritonavir was found in 40% of protocols. The recommended treatment for patients with mild and moderate pneumonias was different antiviral combinations including hydroxychloroquine plus azithromycin (93.3%) or hydroxychloroquine plus lopinavir/ritonavir (79.9%). Different combinations of hydroxychloroquine and lopinavir/ritonavir (46.7%) and triple therapy with hydroxychloroquine, azithromycin, and lopinavir/ritonavir (40%) were the most recommended treatments for patients with severe pneumonia. There were five corticosteroid regimens, which used dexamethasone, methylprednisolone, or prednisone, with different doses and treatment durations. Anakinra was included in seven protocols with six different regimens. All protocols included prophylactic heparin and therapeutic doses for thromboembolism. Higher prophylactic doses of heparin for high-risk patients and therapeutic doses for patients in critical condition were included in 53.3% and 33.3% of protocols, respectively. This study showed that COVID-19 protocols varied widely in several aspects (antiviral treatment, corticosteroids, anakinra, and anticoagulation for high risk of thrombosis or critical situation). Rigorous randomized clinical trials on the proposed treatments are needed to provide consistent evidence.

Glycaemic efficacy and safety of linagliptin for the management of non-cardiac surgery patients with type 2 diabetes in a real-world setting: Lina-Surg study.

Introduction: The use of dipeptidyl peptidase-4 inhibitors in hospitalized patients is an area of active research. We aimed to compare the efficacy and the safety of the basal-bolus insulin regimen versus linagliptin-basal insulin in non-critically ill non-cardiac surgery patients in a real-world setting. Methods: We enrolled patients with type 2 diabetes hospitalized in non-cardiac surgery departments with admission glycated haemoglobin level < 8%, admission blood glucose concentration < 240 mg/dL, and no at-home injectable treatments who were treated with basal-bolus (n = 347) or linagliptin-basal (n = 190) regimens between January 2016 and December 2017. To match patients on the two regimens, a propensity matching analysis was performed. Results: After matching, 120 patients were included in each group. No differences were noted in mean blood glucose concentration after admission (p = .162), number of patients with a mean blood glucose 100-140 mg/dL (p = .163) and > 200 mg/dL (p = .199), and treatment failures (p = .395). Total daily insulin and number of daily insulin injections were lower in the linagliptin-basal group (both p < .001). Patients on linagliptin-basal insulin had fewer hypoglycaemic events (blood glucose < 70 mg/dL) (p < .001). Conclusion: For type 2 diabetes surgery patients with mild to moderate hyperglycaemia without pre-hospitalization injectable therapies, linagliptin-basal insulin was an effective, safe alternative with fewer hypoglycaemic events in real-world practice. Key messages Treatment with basal-bolus insulin regimens is the standard of care for non-critically ill hospitalized patients with type 2 diabetes. A differentiated treatment protocol that takes into account glycaemic control and clinical factors should be implemented in the hospital setting. Linagliptin-basal insulin is an effective, safe alternative with fewer hypoglycaemic events during the hospitalization of non-critically ill non-cardiac surgery patients with T2D in real-world practice.

Trends in Diabetes-Related Potentially Preventable Hospitalizations in Adult Population in Spain, 1997⁻2015: A Nation-Wide Population-Based Study.

We aimed to assess national trends in the rates of diabetes-related potentially preventable hospitalizations (overall and by preventable condition) in the total adult population of Spain. We performed a population-based study of all adult patients with diabetes who were hospitalized from 1997 to 2015. Overall potentially preventable hospitalizations and hospitalizations by diabetes-related preventable conditions (short-term complications, long-term complications, uncontrolled diabetes, and lower-extremity amputations) were examined. Annual rates adjusted for age and sex were analyzed and trends were calculated. Over 19-years-period, 424,874 diabetes-related potentially preventable hospitalizations were recorded. Overall diabetes-related potentially preventable hospitalizations decreased significantly, with an average annual percentage change of 5.1 (95%CI: -5.6-(-4.7%); ptrend < 0.001). Among preventable conditions, the greatest decrease was observed in uncontrolled diabetes (-5.6%; 95%CI: -6.7-(-4.7%); ptrend < 0.001), followed by short-term complications (-5.4%; 95%CI: -6.1-(-4.9%); ptrend < 0.001), long-term complications (-4.6%; 95%CI: -5.1-(-3.9%); ptrend < 0.001), and lower-extremity amputations (-1.9%; 95%CI: -3.0-(-1.3%); ptrend < 0.001). These reductions were observed in all age strata for overall DM-related PPH and by preventable condition but lower-extremity amputations for those <65 years old. There was a greater reduction in overall DM-related PPH, uncontrolled DM, long-term-complications, and lower extremity amputations in females than in males (all p < 0.01). No significant difference was shown for short-term complications (p = 0.101). Our study shows a significant reduction in national trends for diabetes-related potentially preventable hospitalizations in Spain. These findings could suggest a sustained improvement in diabetes care in Spain, despite the burden of these diabetes-related complications and the increase in the diabetes mellitus prevalence.

National trends in diabetes mellitus hospitalization in Spain 1997-2010: Analysis of over 5.4 millions of admissions.

AIMS: To analyze national trends in the rates of hospitalizations (all-cause and by principal discharge diagnosis) in total diabetic population of Spain. METHODS: We carried out a nation-wide population-based study of all diabetic patients hospitalized between 1997 and 2010. All-cause hospitalizations, hospitalizations by principal discharge diagnosis, mean age, Charlson Comorbidity Index, readmission rates and length of hospital stay were examined. Annual rates adjusted for age and sex were analyzed and trends were calculated. RESULTS: Over 14-years-period, all-cause hospitalizations of diabetic patients increased significantly, with an average annual percentage change of 2.5 (95%CI: 1.5-3.5; Ptrend < 0.01). The greatest increase was observed in heart failure (5.4; 95%CI: 4.8-6.0; Ptrend < 0.001), followed by neoplasms (4.9; 95%CI: 3.6-5.8; Ptrend < 0.001), pneumonia (2.7; 95%CI: 2.0-4.0; Ptrend < 0.001), stroke (2.4; 95%CI: 1.6-3.4; Ptrend < 0.001), chronic obstructive pulmonary disease (2.0; 95%CI: 1.4-3.4; Ptrend < 0.001) and coronary artery disease (1.6; 95%CI: 1.1-2.3; Ptrend < 0.01). The adjusted number of all-cause hospitalizations of patients with diabetes per 100,000 inhabitants increased 2.6-fold. The increase in hospitalizations was significantly higher among patients ≥75 years old. Males experienced a greater increase in all-cause, neoplasm, heart failure, chronic obstructive pulmonary disease, and pneumonia hospitalizations (p < 0.01 for all). Hospitalized diabetic patients were progressively older and had more comorbidities, higher readmission rates and shorter hospital stays (p < 0.05 for all). CONCLUSIONS: Hospitalizations of diabetic patients more than doubled in Spain during the study period. Heart failure and neoplasms experienced the greatest annual increases and remained the principal causes of hospitalization, probably associated with advanced age and comorbidities of hospitalized diabetics. Coronary and cerebrovascular diseases experienced a lower annual increase, suggesting an improvement in cardiovascular care in diabetes in Spain.

Use of Linagliptin for the Management of Medicine Department Inpatients with Type 2 Diabetes in Real-World Clinical Practice (Lina-Real-World Study).

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.

Tendencias nacionales en hospitalización por insuficiencia cardiaca de pacientes con diabetes mellitus: periodo 1997-2010 / National trends in heart failure hospitalization rates in patients with diabetes mellitus: 1997-2010

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