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2.
Mol Biol Rep ; 49(3): 2321-2324, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1664478

ABSTRACT

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/complications , Glucosides/therapeutic use , Renin-Angiotensin System/drug effects , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Angiotensin-Converting Enzyme 2/physiology , Clinical Trials, Phase III as Topic , Double-Blind Method , Drug Repositioning , Heart Diseases/prevention & control , Humans , Kidney Diseases/prevention & control , Mitochondria/drug effects , Multicenter Studies as Topic , Oxidative Stress/drug effects , Randomized Controlled Trials as Topic , Receptors, Virus/physiology , Respiratory Insufficiency/etiology , Sodium-Glucose Transporter 2/physiology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology
3.
Curr Med Res Opin ; 38(3): 357-364, 2022 03.
Article in English | MEDLINE | ID: covidwho-1612282

ABSTRACT

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are antidiabetic drugs with numerous pleiotropic and positive clinical effects, particularly regarding a reno-cardiovascular protective effect. More recent studies, including from our laboratory, have highlighted some novel anti-inflammatory activity of SGLT-2 inhibitors. This may confer a theoretical advantage in mitigating excessive cytokine production and inflammatory response associated with serious COVID-19 infection. Specifically, earlier research has demonstrated that SGLT-2 inhibitors are associated with a notable decrease in inflammatory indicators, for example, C-reactive protein, ferritin, and interleukin-6. Furthermore, SGLT-2 inhibitors exhibit a favourable impact on the vascular endothelium function; this could pertinence the prophylaxis of the thrombotic issues that arise in SARS-CoV-2. This review provides an overview of the COVID-19 indirect immune response mechanisms impacting the cardiovascular system and the possible effect of SGLT-2 inhibitors on the management of COVID-19.


Subject(s)
COVID-19 , Inflammation , Sodium-Glucose Transporter 2 Inhibitors , COVID-19/drug therapy , Glucose , Humans , Hypoglycemic Agents/therapeutic use , Inflammation/drug therapy , Inflammation/virology , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
5.
Diabetes Care ; 44(7): 1564-1572, 2021 07.
Article in English | MEDLINE | ID: covidwho-1405389

ABSTRACT

OBJECTIVE: To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODS: We analyzed observational data from SARS-CoV-2-positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018-February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60-day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTS: The study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37-0.80] and 0.66 [0.50-0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONS: Among SARS-CoV-2-positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor/agonists , Sodium-Glucose Transporter 2 Inhibitors , Adult , Aged , COVID-19/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Longitudinal Studies , Male , Middle Aged , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , United States
6.
Sci Rep ; 11(1): 17968, 2021 09 09.
Article in English | MEDLINE | ID: covidwho-1402115

ABSTRACT

The impact of overlapping risk factors on coronavirus disease (COVID-19) severity is unclear. To evaluate the impact of type 2 diabetes (T2D) and obesity on COVID-19 severity, we conducted a cohort study with 28,095 anonymized COVID-19 patients using data from the COVID-19 Research Database from January 1, 2020 to November 30, 2020. The mean age was 50.8 ± 17.5 years, and 11,802 (42%) patients were male. Data on age, race, sex, T2D complications, antidiabetic medication prescription, and body mass index ≥ 30 kg/m2 (obesity) were analysed using Cox proportional hazard models, with hospitalization risk and critical care within 30 days of COVID-19 diagnosis as the main outcomes. The risk scores were 0-4 for age ≥ 65 years, male sex, T2D, and obesity. Among the participants, 11,294 (61.9%) had obesity, and 4445 (15.8%) had T2D. T2D, obesity, and male sex were significantly associated with COVID-19 hospitalization risk. Regarding hospitalization risk scores, compared with those for hospitalization risk score 0 and critical care risk score 0, hazard ratios [95% confidence intervals] were 19.034 [10.470-34.600] and 55.803 [12.761-244.015] (P < 0.001) (P < 0.001), respectively, for risk score 4. Complications from diabetes and obesity increased hospitalization and critical care risks for COVID-19 patients.


Subject(s)
COVID-19/pathology , Critical Care/statistics & numerical data , Diabetes Mellitus, Type 2/pathology , Obesity/pathology , Severity of Illness Index , Aged , Aging/pathology , COVID-19/drug therapy , Diabetes Complications/pathology , Female , Hospitalization/statistics & numerical data , Humans , Hypoglycemic Agents/therapeutic use , Intensive Care Units/statistics & numerical data , Male , Metformin/therapeutic use , Middle Aged , Risk Factors , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , United States
7.
J Fam Pract ; 70(6S): S1-S6, 2021 07.
Article in English | MEDLINE | ID: covidwho-1372160

ABSTRACT

LEARNING OBJECTIVES: At the end of the activity, participants will be able to: • Identify how heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) and associated cardiovascular (CV) risks are interconnected. • Initiate guideline-recommended therapy to reduce CV risk in patients with HF, CKD, and/or T2DM. • Apply evidence for sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) to clinical practice, based on recent and emerging trials. • Review evidence suggesting increased incidence and severity of COVID-19 infection in patients with diabetes.


Subject(s)
Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Cardiovascular System/drug effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/prevention & control , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/prevention & control , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/prevention & control , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Treatment Outcome
8.
Clin Med (Lond) ; 21(4): e327-e231, 2021 07.
Article in English | MEDLINE | ID: covidwho-1357650

ABSTRACT

Obesity is a modifiable risk factor in the development of type 2 diabetes mellitus (T2DM), with the prevalence of both increasing worldwide. This trend is associated with increasing mortality, cardiovascular risk and healthcare costs. An individual's weight will be determined by complex physiological, psychological and societal factors. Assessment by a skilled multidisciplinary team will help identify these factors and will also support screening for secondary causes, assessing cardiovascular risk and identifying sequelae of obesity.A range of treatment options are available for people with obesity and T2DM, including low-calorie diets, medications and bariatric surgery. People should be carefully counselled and personalised care plans developed. Bariatric surgery is an under-utilised resource in this context.Obesity should also be considered when choosing medical therapy for T2DM. Common diabetes medications may lead to weight gain whereas others (such as glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors) support weight loss.Bariatric surgery improves obesity-related complications and all-cause mortality. Diabetes remission is possible after surgery and is recommended by National Institute for Health and Care Excellence in individuals with a body mass index of >35 kg/m2 and recent onset T2DM.


Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/therapy , Humans , Hypoglycemic Agents/therapeutic use , Obesity/complications , Obesity/epidemiology , Obesity/therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
11.
Int J Mol Sci ; 22(14)2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1314668

ABSTRACT

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes.


Subject(s)
COVID-19/therapy , Diabetes Mellitus, Type 2/therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/virology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , SARS-CoV-2/isolation & purification , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
12.
J Cardiovasc Pharmacol ; 78(1): e12-e19, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1232234

ABSTRACT

ABSTRACT: Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (coronavirus disease 2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Clinical Trials, Phase III as Topic , Comorbidity , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Disease Progression , Glucosides/adverse effects , Humans , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Treatment Outcome
13.
Diabet Med ; 38(2): e14458, 2021 02.
Article in English | MEDLINE | ID: covidwho-1214788

ABSTRACT

Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI ≥27 kg/m2 . Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration among other precipitating factors for diabetic ketoacidosis.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetic Ketoacidosis/epidemiology , Overweight/metabolism , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Drug Therapy, Combination , Glucosides/therapeutic use , Glycosides/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Overweight/complications , Practice Guidelines as Topic , United Kingdom
14.
Diabetes Obes Metab ; 23(4): 886-896, 2021 04.
Article in English | MEDLINE | ID: covidwho-1171152

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS: DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS: DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Cardiovascular Diseases/prevention & control , Glucosides/therapeutic use , Kidney Diseases/prevention & control , Mortality , Respiratory Insufficiency/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Atherosclerosis/epidemiology , COVID-19/complications , COVID-19/epidemiology , Cardiometabolic Risk Factors , Cardiovascular Diseases/etiology , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Double-Blind Method , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Kidney Diseases/etiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/epidemiology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Treatment Outcome
15.
Int J Clin Pharm ; 43(3): 764-767, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1137159

ABSTRACT

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering agents which have changed the landscape of diabetes therapy, due to their remarkable cardiorenal protective properties. The attack of severe acute respiratory syndrome coronavirus 2 on the heart and kidneys shares similarities with diabetes; therefore, the notion that SGLT2i might have a role in the future management of Coronavirus Disease 2019 (COVID-19) is based on a solid pathophysiological hypothesis. SGLT2i have been proved to decrease the expression of proinflammatory cytokines, ameliorate oxidative stress and reduce sympathetic activity, thus resulting in downregulation of both systemic and adipose tissue inflammation. On the other hand, they have been linked to an increased risk of euglycemic diabetic ketoacidosis. Therefore, the efficacy and safety of SGLT2i in COVID-19 are still debatable and remain to be clarified by ongoing randomized trials, to assess whether the benefits of treatment with these drugs outweigh the potential risks.


Subject(s)
COVID-19/complications , Diabetes Mellitus, Type 2/complications , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/virology , Humans , Risk Assessment , Sodium-Glucose Transporter 2 Inhibitors/adverse effects
16.
Circ Heart Fail ; 14(3): e007767, 2021 03.
Article in English | MEDLINE | ID: covidwho-1136135

ABSTRACT

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.


Subject(s)
Canagliflozin/therapeutic use , Heart Failure/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Telemedicine , Actigraphy/instrumentation , Canagliflozin/adverse effects , Double-Blind Method , Exercise Tolerance/drug effects , Fitness Trackers , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Mobile Applications , Quality of Life , Randomized Controlled Trials as Topic , Recovery of Function , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Stroke Volume/drug effects , Telemedicine/instrumentation , Time Factors , Treatment Outcome , United States , Ventricular Function, Left/drug effects
17.
Br J Clin Pharmacol ; 87(10): 3643-3646, 2021 10.
Article in English | MEDLINE | ID: covidwho-1121364

ABSTRACT

Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.


Subject(s)
COVID-19 , Diabetes Mellitus , Sodium-Glucose Transporter 2 Inhibitors , Blood Glucose , Glucose , Humans , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
18.
Circ Heart Fail ; 14(3): e007048, 2021 03.
Article in English | MEDLINE | ID: covidwho-1119347

ABSTRACT

BACKGROUND: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. METHODS: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. RESULTS: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (P=0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (P=0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (P=0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. CONCLUSIONS: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.


Subject(s)
Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Heart Failure/drug therapy , Hospitalization , Kidney/drug effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Aged , Aged, 80 and over , Benzhydryl Compounds/adverse effects , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19 , Creatinine/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/physiopathology , Early Termination of Clinical Trials , Female , Glucosides/adverse effects , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Japan , Kidney/physiopathology , Male , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Time Factors , Treatment Outcome
20.
Diabetes Obes Metab ; 23(6): 1397-1401, 2021 06.
Article in English | MEDLINE | ID: covidwho-1050340

ABSTRACT

Incretin-based therapies, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been hypothesized to exert beneficial effects on COVID-19 outcomes due to anti-inflammatory properties. In this population-based cohort study, we retrieved data from nationwide registries on all individuals diagnosed with severe acute respiratory syndrome coronavirus 2 infection up to 1 November 2020. For individuals with diabetes, we examined the impact of use of GLP-1 RAs (n = 370) and DPP-4i (n = 284) compared with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) (n = 342) on risk of hospital admission and severe outcomes. Relative risks (RRs) were calculated after applying propensity score weighted methods to control for confounding. Current users of GLP-1 RAs had an adjusted RR of 0.89 (95% confidence interval 0.34-2.33), while users of DPP-4i had an adjusted RR of 2.42 (95% confidence interval 0.99-5.89) for 30-day mortality compared with SGLT-2i use. Further, use of GLP-1 RAs or DPP-4i compared with SGLT-2i was not associated with decreased risk of hospital admission. Thus, use of incretin-based therapies in individuals with diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was not associated with improved clinical outcomes.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Sodium-Glucose Transporter 2 Inhibitors , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucagon-Like Peptide-1 Receptor , Humans , Hypoglycemic Agents/therapeutic use , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
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