Management of diabetes in patients with COVID-19
Authors: Jean-Daniel Lalau, Abdallah Al-Salameh
Journal: The Lancet Diabetes & Endocrinology (2020)

We read with interest the recommendations on the management of diabetes in patients with COVID-19 by Stefan Bornstein and colleagues.1Bornstein SR Rubino F Khunti K et al.Practical recommendations for the management of diabetes in patients with COVID-19.Lancet Diabetes Endocrinol. 2020; 8: 546-550Summary Full Text Full Text PDF PubMed Scopus (623) Google Scholar However, their suggestion of discontinuing metformin in patients with severe symptoms of COVID-19 (to reduce the risk of lactic acidosis) raises a number of issues. We believe that it is important to maintain a thoughtful approach to metformin therapy in patients with diabetes and COVID-19. After the synthesis of the first glucose-lowering biguanides in the 1920s, metformin was rediscovered in the 1940s for the treatment of malaria. In 1949, a dimethylbiguanide preparation (flumamine) was used to treat influenza virus infections. Since then, metformin has shown adjuvant efficacy in malaria, tuberculosis, hepatitis C virus infection, and Zika virus infection, indicating that it has considerable potential as an antimicrobial. Of note, metformin is reportedly one of the drugs that targets human host factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the mTOR pathway.2Gordon DE Jang GM Bouhaddou M et al.A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.Nature. 2020; (published online April 30.)https://doi.org/10.1038/s41586-020-2286-9Crossref PubMed Scopus (2936) Google Scholar Metformin has direct and indirect immunosuppressive effects. In particular, metformin reduces the secretion of pro-inflammatory cytokines (IL-6, IL-1β, CXCL1, and CXCL2) by macrophages. These cytokines are involved in the development of acute respiratory distress syndrome in COVID-19. Moreover, lung inflammation in COVID-19 can lead to fibrosis. Metformin is known to reverse established fibrosis in various lung models by facilitating the deactivation and apoptosis of myofibroblasts.3Rangarajan S Bone NB Zmijewska AA et al.Metformin reverses established lung fibrosis in a bleomycin model.Nat Med. 2018; 24: 1121-1127Crossref PubMed Scopus (384) Google Scholar Generally, metformin is considered to act as a cell protector; it modulates energy metabolism (thus attenuating the harmful effects of stress on mitochondrial function), activates AMP-activated protein kinase (potentiating the autophagic process), scavenges reactive oxygen species, and modulates dysbiosis. These characteristics might explain why metformin has been shown to be associated with a relative reduction in mortality among patients with diabetes in the intensive care unit.4Christiansen C Johansen M Christensen S O'Brien JM Tønnesen E Sørensen H Preadmission metformin use and mortality among intensive care patients with diabetes: a cohort study.Crit Care. 2013; 17: R192Crossref PubMed Scopus (42) Google Scholar Finally, severe infections are associated with insulin resistance and hyperglycaemia (even in patients without diabetes), whereas tight blood glucose control is essential for reducing mortality among patients who are critically ill. Hence, we suggest that investigators in ongoing cohort studies should check whether metformin is associated with a favourable outcome in patients with diabetes. Pending these analyses, we recommend that metformin treatment should be maintained in patients with diabetes who are hospitalised for COVID-19, as long as they have not developed concomitant kidney and liver failure. Kidney failure leads to metformin accumulation and liver failure reduces lactate elimination, increasing the risk of lactic acidosis.5Lalau J-D Kajbaf F Protti A Christensen MM De Broe ME Wiernsperger N Metformin-associated lactic acidosis (MALA): moving towards a new paradigm.Diabetes Obes Metab. 2017; 19: 1502-1512Crossref PubMed Scopus (88) Google Scholar We declare no competing interests. Management of diabetes in patients with COVID-19 – Authors' replyWe are pleased to learn about the interest in our paper on the practical recommendations for the management of diabetes in patients with COVID-19.1 These Correspondences address important aspects regarding the use of medications and the risk of hypoglycaemia or obesity, and we are thankful for these comments. Full-Text PDF Management of diabetes in patients with COVID-19We read with great interest the Personal View by Stefan Bornstein and colleagues1 on the management of diabetes in patients with COVID-19. During these unprecedented times, more guidance is required to care for this high-risk population. The authors recommend intensification of glucose control to prevent COVID-19, suggesting an HbA1c of less than 53 mmol/mol (<7%) and plasma glucose concentration of 4–8 mmol/L (72–144 mg/dL) for most patients, and 5–8 mmol/L (90–144 mg/dL) for frail patients. These glycaemic goals for the older population are much tighter than suggested in most guidelines. Full-Text PDF Practical recommendations for the management of diabetes in patients with COVID-19Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. Full-Text PDF Management of diabetes in patients with COVID-19We read with interest the practical recommendations for management of diabetes in patients with COVID-19 by Stefan Bornstein and colleagues1 in The Lancet Diabetes & Endocrinology. However, in the panel describing special considerations for anti-diabetic drugs, we note that two commonly used groups, sulfonylureas and pioglitazone, are missing. Of these, pioglitazone, a PPAR-γ agonist, merits further discussion because it interacts with both the mechanisms that might play a role in patients with diabetes with COVID-19, as described by Bornstein and colleagues. Full-Text PDF Management of diabetes in patients with COVID-19The recent Personal View by Stefan Bornstein and colleagues1 highlights possible susceptibility factors in patients with diabetes and obesity that could predispose to severe COVID-19-related illness. The authors incorporated useful general management guidance, but we feel that the descriptions of acute presentations were not sufficiently detailed to aid clinical management. We wish to expand on the acute metabolic presentations related to hyperglycaemia, which have been challenging to manage in the acute setting. Full-Text PDF Management of diabetes in patients with COVID-19Stefan Bornstein and colleagues1 seem to be the first to react to an unprecedented challenge regarding management of diabetes in patients with COVID-19 by offering practical recommendations. The authors state that patients with diabetes have an increased risk of severe COVID-19 complications, including acute respiratory distress syndrome. Full-Text PDF