Management of diabetes in patients with COVID-19
Authors: Jagat J Mukherjee, Kalyan K Gangopadhyay, Subir Ray
Journal: The Lancet Diabetes & Endocrinology (2020)

We read with interest the practical recommendations for management of diabetes in patients with COVID-19 by Stefan Bornstein and colleagues1Bornstein 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 (616) Google Scholar 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.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 (616) Google Scholar In addition, a substantial minority of people with diabetes in the UK,2Wilkinson S Douglas I Stirnadel-Farrant H et al.Changing use of antidiabetic drugs in the UK: trends in prescribing 2000–2017.BMJ Open. 2018; 8e022768Crossref PubMed Scopus (74) Google Scholar and a considerable proportion worldwide, use pioglitazone. Pioglitazone upregulates expression of ACE2 in rat tissues,3Zhang W Xu YZ Liu Bo et al.Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis.ScientificWorldJournal. 2014; 2014603409PubMed Google Scholar leading to speculation that its use might increase susceptibility to, and severity of, COVID-19, because ACE2 acts as a co-receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the cell. However, apart from ACE2 upregulation in insulin-sensitive tissues in animals, namely the liver, adipose tissue, and skeletal muscle, there is no evidence that pioglitazone upregulates expression of ACE2 in alveolar cells. Alternatively, as described by 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 (616) Google Scholar by increasing ACE2 expression in insulin-sensitive tissues, pioglitazone might help ameliorate the harmful effects of excess angiotensin II. In addition, using homology modelling and molecular docking techniques, Wu and colleagues4Wu C Liu Y Yang Y et al.Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods.Acta Pharm Sini B. 2020; 10: 766-788Crossref PubMed Scopus (1603) Google Scholar have shown that pioglitazone is a potential inhibitor of 3-chymotrypsin-like protease, which is essential for RNA synthesis and replication of SARS-CoV-2. However, this software-based prediction of pioglitazone as a potential inhibitor of SARS-CoV-2 RNA synthesis and replication needs validation in both in-vitro and in-vivo studies. People with diabetes and COVID-19 are at a higher risk of SARS-CoV-2-driven hyperinflammation and cytokine storm syndrome.5Guo W Li M Dong Y et al.Diabetes is a risk factor for the progression and prognosis of COVID-19.Diabetes Metab Res Rev. 2020; (published online March 31.)https://doi.org/10.1002/dmrr.3319Crossref Scopus (943) Google Scholar Pioglitazone might play an important role by moderating the host inflammatory response on multiple fronts. PPAR-γ agonists decrease the secretion of various pro-inflammatory cytokines, including TNF-α, IL-1, and IL-6 in the monocytes and macrophages. Furthermore, animal studies have shown that pioglitazone can suppress TNF-α and IL-6 generation in adipose tissue. However, more research is needed to substantiate these benefits in humans. Pioglitazone is an inexpensive anti-diabetic drug, used widely around the globe. It has the potential to do more benefit than harm, and, in our view, it can be safely continued in people with diabetes and COVID-19, except in specific conditions in which its use is not recommended, including symptomatic heart failure and liver dysfunction with significantly elevated transaminases. 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-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 Management of diabetes in patients with COVID-19We read with interest the recommendations on the management of diabetes in patients with COVID-19 by Stefan Bornstein and colleagues.1 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. Full-Text PDF