key: cord-0892147-nkwwwu5e authors: Rizvi, Ali A.; Janez, Andrei; Al Mahmeed, Wael; Rizzo, Manfredi title: Diabetes and COVID-19: A Tale of 2 Pandemics date: 2021-06-28 journal: J Cardiovasc Pharmacol DOI: 10.1097/fjc.0000000000001047 sha: 13e8835f1f3afc4d060bfd2f1c942aec4e49503b doc_id: 892147 cord_uid: nkwwwu5e nan The enormity of information and the rapidly changing scenarios in the hospital setting as well as ambulatory care has created confusion at times. On the bright side, knowledge from the frontlines has been a ready source of data that has armed clinicians and investigators to study and apply the evidence for the benefit of patients. In this regard, the role of diabetes treatments such as insulin, metformin, sodium-glucose transport protein 2 inhibitors, and incretin-based therapies (IBTs), ie, glucagon-like peptide-1 receptor agonists (GLP1-RAs) and dipeptidyl peptidase-4 inhibitors, in COVID-19 infection, particularly in influencing the course of illness, has generated keen interest. 6 It is understood that insulin therapy has been the mainstay for maintaining optimal glucose control in the frequently fulminant hyperglycemia and acute decompensation seen in patients with COVID-19, either with or without a history of diabetes. Intravenous and intensive multiple daily insulin injection regimens have been particularly effective, and various organizations, institutions, and health care systems have established guidelines customized to the specific clinical situation. 7 The role of traditional therapies, such as the sulfonylureas and metformin, has been studied as well. However, it is in the realm of the more recently introduced pharmacologic agents that IBTs have been hypothesized to exert beneficial effects on COVID-19 outcomes because of anti-inflammatory properties, and furthermore, dipeptidyl peptidase-4 receptors have been found to have interactions with the SARS-CoV-2 virus; insights into receptor-mediated actions have led to postulated mechanisms that could explain the potential benefits of IBTs in COVID-19. 8 In addition to improving hyperglycemia, IBTs may confer additional protection against the short-term and long-term consequences of COVID-19. Although there are intensive debates regarding safety of different classes of antidiabetics at the advent of COVID-19, multiple ongoing studies are evaluating the adjuvant role of various antidiabetic agents such as IBTs in reducing the severity of COVID-19. Dapagliflozin, an SGLT-2 inhibitor, has been a recent addition to the trend, and the present article is an accompanying editorial of the interesting review made by Anastasiou and coauthors on dapagliflozin and COVID-19 progression in high-risk patients with or without diabetes, where they lay out the evidence for the cardioprotective and nephroprotective effects of this medication and discuss the potential favorable impact of dapagliflozin on COVID-19 and its complications. 9 There is strong evidence that subjects with cardiovascular or kidney diseases who contract COVID-19 have a worse prognosis than those without these underlying conditions. Therefore, it is mandatory to preserve the integrity of the renal and cardiovascular system in patients with type-2 diabetes affected by SARS-CoV-2. 4 GLP1-RAs and sodiumglucose transport protein 2 inhibitors have proven cardiorenal-metabolic benefit; in this context, Anastasiou and coauthors 9 discussed the DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19) trial, designed to investigate the impact of dapagliflozin on COVID-19 progression. However, trial results did not achieve statistical significance for the primary endpoints of prevention of organ dysfunction, reduction in all-cause mortality, and improvement in the clinical status (ranging from early recovery to death) at 30 days. 10 It has been shown that the duration of lockdown and social distancing measures are directly proportional to the worsening of glycemic control and diabetesrelated complications, possibly through aggravation of overweight and obesity. The importance of GLP1-RAs use in the prevention of weight gain is relevant in this regard. 8 In addition, GLP1-RAs have demonstrated significant antiinflammatory and antiadipogenic effects, partly through decreasing insulin resistance-actions that could potentially be beneficial during COVID infection. 8 The French-Algerian philosopher and writer Albert Camus, in his prophetic work "The Plague," describes the ravages of a rat-borne contagion on the population of a fictitious town as seen through the eyes of the physician-narrator. 11 After the catastrophe has past, the chilling ending notes that ".the plague bacillus never dies or disappears for good; that it can lie dormant for years.," ready to resurface when the opportunity arises. Likewise, the current situation, a daunting overlap of an inexorably worsening metabolic disease and a mysterious infection, is not likely to be humanity's last encounter with a figurative bacillus. Surely, the double health risk of diabetes and COVID-19 infection in modern times is a unique challenge for clinicians and researchers alike. The rapidly evolving fund of knowledge and evidence regarding antidiabetes medication use in these settings behooves us to put all the pieces of the puzzle together in a safe and expeditious manner for the benefit of our patients. The Perfect Storm: A True Story of Men against the Sea Factors leading to high morbidity and mortality of COVID-19 in patients with type 2 diabetes COVID-19 and diabetes management: what should be considered? COVID-19 and diabetes mellitus: from pathophysiology to clinical management Clinical management of diabetes mellitus in the era of COVID-19: practical issues, peculiarities and concerns The 2019-2020 novel coronavirus (severe acute respiratory syndrome coronavirus 2) pandemic: a joint American College of Academic international Medicine-World Academic Council of Emergency Medicine Multidisciplinary COVID-19 Working Group consensus paper Incretin-based therapies role in COVID-19 era: evolving insights Could dapagliflozin attenuate COVID-19 progression in high-risk patients with or without diabetes? Behind DARE-19 concept La Peste (The Plague)