Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial

Kosiborod, M.N. et al | 2021 | Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial | The Lancet Diabetes & Endocrinology | DOI:https://doi.org/10.1016/S2213-8587(21)00180-7

The DARE-19 trial has evaluated the efficacy and safety of dapagliflozin in patients who had at least one cardiometabolic risk factor, such as hypertension and type 2 diabetes among others, and who were hospitalised with COVID-19.

At screening, 636 patients (50·9 per cent ) had type 2 diabetes. The prespecified subgroup analyses for the primary outcome of prevention and recovery are shown in, and were generally consistent with the main findings, including in patients with and without diabetes, although there was heterogeneity noted by sex. Diabetic ketoacidosis was reported in two patients in the dapagliflozin group both of whom had type 2 diabetes at baseline; these events were non-severe and resolved after study medication discontinuation.

To the authors’ knowledge, DARE-19 is the first, large randomised controlled trial to evaluate efficacy and safety of SGLT2 inhibitors in patients hospitalised with COVID-19 and has implications for clinical practice and future research. Dapagliflozin did not significantly reduce the proportion of patients with organ dysfunction or death or who experienced improved recovery. Although we observed numerically fewer events of organ dysfunction or death in patients who received dapagliflozin as compared with placebo, this difference was not statistically significant, and might not be generalisable to other populations. Importantly, dapagliflozin was well tolerated in one of the highest risk (with respect to organ failure and death) patient populations ever to be treated with SGLT2 inhibitors.


Implications of all the available evidence

Their study shows that dapagliflozin was well tolerated, with no new safety concerns identified in this acutely ill patient population. Therefore, for patients already receiving SGLT2 inhibitors before a COVID-19 diagnosis, our findings support continuation of this treatment, as long as patients are monitored. Because SGLT2 inhibitors do not have a direct anti-viral effect on SARS-CoV2, our findings (although not conclusive) suggest a need for future trials to determine whether dapagliflozin might provide organ protection in non-COVID-19 hospitalised patients at high risk for progressing to critical illness (Source: Kosiborod et al, 2021).

Primary paper Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial

Treatment of type 2 diabetes: challenges, hopes, and anticipated successes

Nauck, M.A, Wefers, J. & Meier, J.J. | 2021 | Treatment of type 2 diabetes: challenges, hopes, and anticipated successes | The Lancet Diabetes & Endocrinology | DOI:https://doi.org/10.1016/S2213-8587(21)00113-3

Summary

Despite the successful development of new therapies for the treatment of type 2 diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors, the search for novel treatment options that can provide better glycaemic control and at reduce complications is a continuous effort. The present Review aims to present an overview of novel targets and mechanisms and focuses on glucose-lowering effects guiding this search and developments. We discuss not only novel developments of insulin therapy (eg, so-called smart insulin preparation with a glucose-dependent mode of action), but also a group of drug classes for which extensive research efforts have not been rewarded with obvious clinical impact. We discuss the potential clinical use of the salutary adipokine adiponectin and the hepatokine fibroblast growth factor (FGF) 21, among others. A GLP-1 peptide receptor agonist (semaglutide) is now available for oral absorption, and small molecules activating GLP-1 receptors appear on the horizon. Bariatric surgery and its accompanying changes in the gut hormonal milieu offer a background for unimolecular peptides interacting with two or more receptors (for GLP-1, glucose-dependent insulinotropic polypeptide, glucagon, and peptide YY) and provide more substantial glycaemic control and bodyweight reduction compared with selective GLP-1 receptor agonists. These and additional approaches will help expand the toolbox of effective medications needed for optimising the treatment of well delineated subgroups of type 2 diabetes or help develop personalised approaches for glucose-lowering drugs based on individual characteristics of our patients.

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Six-figure funding secured to develop chatbot for young people with type 1 diabetes

Sheffield Hallam University | July 2021 | Six-figure funding secured to develop chatbot for young people with type 1 diabetes

Researchers from Sheffield Hallam University and Sheffield Children’s Hospital have secured funding of £800 000 to develop the first NHS-approved chatbot virtual assistant for young people with type 1 diabetes who are moving from paediatric to adult care

Over 50 per cent of young people with chronic health conditions report inadequate support and services during their transition to adult healthcare.

One-third of young people have poor diabetes control by the time of their first adult clinic visit. 

To redress this, the NIHR- funded chatbot will provide support during the transition to adult diabetes services through 24/7 access to relevant, engaging and clinically-approved information that meets individual needs and preferences.

To develop the chat bot the lead authors of the study- Professor Veronica Swallow and her colleagues will provide training and support for the project’s Expert User Advisory Group. They will conduct qualitiative research, focus groups with young people living with type 1 diabetes to find out what they would like included in the chatbot, this will be followed by a trial of young people’s views on the chatbot. Qualitative interviews with the young people and their parents will also be undertaken after the trial will be used to inform the next stage of the project and to see if using the chatbot has helped young people feel better about self-management.

Adapted from Sheffield Hallam’s press release, available in full from the University

Six-figure funding secured to develop chatbot for young people with type 1 diabetes

Diabetes, Obesity, COVID-19, Insulin, and Other Antidiabetes Drugs #Covid19RftLks

 Dandona, P. & Ghanim, H. | 2021 | Diabetes, Obesity, COVID-19, Insulin, and Other Antidiabetes Drugs | Diabetes Care |   dci210003; DOI: 10.2337/dci21-0003

This review published in the journal Diabetes Care aims to explain some of the processes involved in chronic inflammation and identifies potential strategies to combat them.

Paper available from Diabetes Care

Diabetes and COVID-19: Population impact 18 months into the pandemic

Diabetes Care | July 2021

Eighteen months into the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic, epidemiologic studies indicate that diabetes is a central contributor to severe COVID-19 morbidity, and, conversely, COVID-19 has had a devastating effect on the population with diabetes.

In this literature synthesis, the authors summarize the relationship of diabetes to COVID-19–related morbidity and mortality, discuss the predictors of severe adverse outcomes and implications of the overall pandemic, and critique the current status of and identify needs for epidemiologic studies for the next phase of the pandemic.

Full paper: Diabetes and COVID-19: Population impact 18 months into the pandemic

Pharmacists, nurses and educators ‘key’ to combating type 2 diabetes therapeutic inertia

NIHR | July 2021 | Pharmacists, nurses and educators ‘key’ to combating type 2 diabetes therapeutic inertia

UK researchers from Leicester and a number of states in the United States, as well as the American Diabetes Association (ADA) Overcoming Therapeutic Inertia initiative led by Professor Kamlesh Khunti investigated the effect of interventions to overcome clinical inertia on glycaemic control in type 2 diabetes, focusing on reduction of HbA1c, they evaluate the quality of the evidence and the effect of these interventions on glycaemic control. The reviewers identified 36 interventions for inclusion in this systematic review, and arranged them by the following categories:

  • Pharmacist-based interventions – including medication reviews and make guideline-based adjustments to medications
  • Care management and patient education interventions – looking at virtual coaching, or patient education, often supported by remote or telemonitoring
  • Physician-based interventions – focused on education in-person, written educational materials.
  • Nurse- or CDE-based interventions – using evidence-based protocols to provide diabetes management including treatment initiation or intensification.

They report the most effective interventions were those within which pharmacists, nurses and diabetes educators had autonomy to address therapeutic inertia and improving HbA1c in partnership with primary care provider (Source NIHR & Powell et al, 2021).

Abstract

Aims

To systematically investigate the effect of interventions to overcome therapeutic inertia on glycaemic control in individuals with type 2 diabetes.

Materials and Methods

We electronically searched for randomized controlled trials or quasi-experimental studies published between January 1, 2004 and December 31, 2019 evaluating the effect of interventions on glycated haemoglobin (HbA1c) control. Characteristics of included studies and HbA1c difference between intervention and control arms (main outcome) were extracted. Interventions were grouped as: care management and patient education; nurse or certified diabetes educator (CDE); pharmacist; or physician-based.

Results

Thirty-six studies including 22 243 individuals were combined in nonlinear random-effects meta-regressions; the median (range) duration of intervention was 1 year (0.9 to 36 months). Compared to the control arm, HbA1c reduction ranged from: −17.7 mmol/mol (−1.62 per cent ) to −4.4 mmol/mol (−0.40 per cent %) for nurse- or CDE-based interventions; −13.1 mmol/mol for care management and patient education interventions; −9.8 mmol/mol to −6.6 mmol/mol (−0.60 per cent ) for pharmacist-based interventions; and −4.4 mmol/mol (−0.40%) to 2.8 mmol/mol (0.26 per cent ) for physician-based interventions. Across the included studies, a reduction in HbA1c was observed only during the first year and in individuals with preintervention HbA1c >75 mmol/mol (9 per cent).

Conclusions

The most effective approaches to mitigating therapeutic inertia and improving HbA1c were those that empower nonphysician providers such as pharmacists, nurses and diabetes educators to initiate and intensify treatment independently, supported by appropriate guidelines.

Primary paper Strategies for overcoming therapeutic inertia in type 2 diabetes: A systematic review and meta-analysis

NIHR Pharmacists, nurses and educators ‘key’ to combating type 2 diabetes therapeutic inertia

Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020–March 2021 #Covid19RftLks

Kompaniyets, L. et al | 2021 | Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020–March 2021 | Preventing Chronic Disease | 18 |10123 | DOI: http://dx.doi.org/10.5888/pcd18.210123external icon.

The research team behind this study set out to identify the incidence of underlying medical conditions, such as essential hypertension, obesity, chronic kidney disease and diabetes, among hospitalized patients with COVID-19 and their associations with severe illness. The experts found that half of these frequent underlying medical conditions among adults hospitalized with COVID-19 were associated with severe illness. They report that obesity, diabetes with complication, and the presence of multiple chronic conditions were the strongest chronic risk factors for death from Covid-19 among hospitalized adults. diabetes with complication was associated with 26 per cent higher (95 per cent CI, 24 per cent –28 per cent ); diabetes without complication was associated with a 6 per cent lower risk of death. The authors suggest that this information can better inform clinical practice and public health priorities, such as identifying populations for focused prevention efforts and potential vaccine prioritization.

Abstract

Introduction

Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 illness.

Methods

We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions.

Results

Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0 per cent) were patients with COVID-19, of whom 94.9 per cent had at least 1 underlying medical condition. Essential hypertension (50.4 per cent ), disorders of lipid metabolism (49.4 per cent ), and obesity (33.0 per cent ) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio [aRR] equal to 1.30; 95 per cent CI, 1.27–1.33), anxiety and fear-related disorders (aRR = 1.28; 95 per cent CI, 1.25–1.31), and diabetes with complication (aRR equal to 1.26; 95 per cent CI, 1.24–1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95 per cent CI, 1.41–1.67) for patients with 1 condition to 3.82 (95 per cent CI, 3.45–4.23) for patients with more than 10 conditions (compared with patients with no conditions).

Conclusion

Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness.

Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020–March 2021