Medication Prescribed Diabetes Mellitus amid the COVID-19 Pandemic in Greece: Data and Challenges Along the Way

The COVID-19 pandemic has led to an intricate disruption of the provision of healthcare worldwide. In Greece, as per March 2021, patient visits to the outpatient medical facilities have ceased due to the widely applied lockdowns and restrictions imposed by the government. Therefore, it has become increasingly hard to sustain the same quality of care to individuals with Diabetes mellitus (DM), a chronic and challenging condition affecting up to 10% of the Greek population.¹

Medication-prescribed diabetes, in particular, concerns 720,764 individuals in the country. Emerging evidence regarding the interplay between COVID-19 and anti-diabetic medications has compelled healthcare professionals to reconsider the treatment of these individuals. Although they are at high risk of contracting SARS-CoV-2, at the same time they have limited or no access to healthcare due to the COVID-19 restrictions. This paper reflects on the authors’ relevant experience in the outpatient diabetes center of the hospital “Tzaneio” in the city of Piraeus, Greece during the trying times of the COVID-19 pandemic.

A recently published review study of our team (Sevdalis et al., 2020) as well as an ongoing observational study in our department suggests that specific non – insulin regimens may decrease COVID-19 inpatient mortality. Particularly, SGLT2 inhibitors, GLP-1 analogues, metformin, pioglitazone and DPP4 inhibitors seem to have a positive effect on patients’ response to COVID-19.² Evidence from previous studies suggests that SGLT2 inhibitors and GLP-1 analogues can decrease the likelihood of a generalized inflammatory syndrome in respiratory infection (Rizzo et al., 2018). Previous studies have established that metformin and pioglitazone can decrease the viral load in several infections including hepatitis C, as well as potential attenuating effects on liver damage in COVID-19.^3,4 Ongoing research is examining whether the findings for hepatitis apply to SARS-CoV-2 as well.²

When it comes to DPP4 proteins, it has been established that they modulate the activation of T lymphocytes promoting the CD86 and NF-κβ mediated inflammatory pathways. This stated, DPP4 inhibitors may decrease the risk of developing the COVID-19 inflammatory syndrome. In the past DPP4 protein has been identified as a MERS-COV receptor, however existing studies have failed to prove such an activity in the context of COVID-19 infection.⁵

A brief report presenting early results from a nationwide cohort in South Korea indicated that COVID-19 mortality among diabetic outpatients on DPP4 inhibitors was lower in comparison to patients receiving other second or third line non-insulin agents.⁶

Overall, it appears that specific non – insulin regimens can have a positive impact on COVID-19 inpatient mortality because of their effect on systemic inflammation in infectious diseases. Particularly, DPP4is and GLP1 analogues appear to effectively control glucose levels in both diabetic inpatients and outpatients with mild or moderate COVID-19 infection.⁷ However, the data supporting the use of these agents instead of insulin in diabetic patients with severe COVID-19 disease are not sufficient.⁸ These observations are in line with review studies and metanalyses published in the beginning of the pandemic.⁹  So far, we have noted similar trends in patients with type 2 diabetes admitted to the COVID-19 ward of our hospital. In this study, we have not observed different outcomes in terms of the other risk factors reported by Agarwal et. al (2020).¹⁰

Non-insulin regimens are the treatment of choice for a great number of patients worldwide, and in Greece as discussed. In most cases, these patients strive to maintain a moderate or good glycemic control, so as to avoid insulin dependence and subsequent health outcomes.¹¹ Amid the pandemic, with an increasing rate of patients with type 2 diabetes admitted to the COVID-19 wards, understanding the effect of non – insulin regimens on COVID-19 inpatient mortality is of high concern for both physicians and patients. While further research is necessary to establish the positive impact of the aforementioned antidiabetic regimens, we might consider prioritizing them over other medications when applicable. The latter needs to become a priority taking into account that diabetes was highlighted as a risk factor for ICU admission in a recent study developing a COVID-19 critical illness risk score among patients in a Greek COVID-19 reference department.¹²

Improving diabetes care during the pandemic faces additional barriers, due to the limited access of the concerned patients to healthcare. In the previous months, telemedicine has been used in the authors’ department to support patients with diabetes – associated continuous monitoring wearable devices. Although this infrastructure exists, additional personnel and funding would be necessary to expand it to individuals receiving anti-diabetic medications. Not only are the individuals concerned numerous and in need of receiving basic telehealth training, but in their case teleconsultations would lack the data input of wearables, making any decision more subjective and hence more chancy. Additional burden stems from mental health and eating disorders observed among patients with diabetes in Greece during the prolonged lockdowns. While an ongoing multicenter clinical trial is assessing the extent and the impact of these implications, practitioners need to take into account the willingness and capacity of each individual to adhere to antidiabetic treatment¹³. Telemedicine can help physicians check on such patients, modifying their treatment plan accordingly or referring them to mental health professionals in a timely manner.

Closing, it is apparent that, at least for the time being, the current healthcare landscape is COVID-19-centered and many aspects of it still have to adapt further to the current circumstances. When it comes to DM, patients and clinicians face a two-pronged challenge. While maintaining good glycemic control is inevitably harder during this period, it is vital that concurrent treatment regimens get correlated with COVID-19 outcomes to ensure maximal protection of a group of patients that is vulnerable, yet very significant numerically. Moreover, advances in the field of telemedicine and its increased utilisation is something that could stay even after this pandemic, and based on our experience it would be a welcome addition to the infrastructure of Greek diabetes care.