Importance of diabetes management during the COVID-19 pandemic

ABSTRACT

Uncontrolled diabetes and/or hyperglycemia is associated with severe COVID-19 disease and increased mortality. It is now known that poor glucose control before hospital admission can be associated with a high risk of in-hospital death. By achieving and maintaining glycemic control, primary care physicians (PCPs) play a critical role in limiting this potentially devastating outcome. Further, despite the hope that mass vaccination will help control the pandemic, genetic variants of the virus are causing surges in some countries. As such, PCPs will treat an increasing number of patients with diabetes who have symptoms of post–COVID-19 infection, or even have new-onset type 2 diabetes as a result of COVID-19 infection. However, much of the literature published focuses on the effects of COVID-19 in hospitalized patients, with few publications providing information and advice to those caring for people with diabetes in the primary care setting. This manuscript reviews the current knowledge of the risk and outcomes of individuals with diabetes who are infected with COVID-19 and provides information for PCPs on the importance of glucose control, appropriate treatment, and use of telemedicine and online prescription delivery systems to limit the potentially devastating effects of COVID-19 in people with hyperglycemia.

KEYWORDS:

• COVID-19
• diabetes
• hyperglycemia
• hemoglobin A1c
• primary care

1.0. Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus that causes COVID-19, which in some people can cause complex multi-system disease and death. As of early-August 2021, the virus has spread to over 200 countries/regions, has infected over 199 million people, and has caused over 4.2 million deaths [1]. In the United States (US) there have been over 35.1 million confirmed cases and nearly 614,000 deaths [1].

In the era of COVID-19, having diabetes and/or uncontrolled hyperglycemia is associated with poorer outcomes and more severe disease. A meta-analysis of 1558 patients from six studies identified diabetes as one of several comorbidities (including hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease) that are major risk factors for COVID-19 [2]. Having diabetes has been linked with increased mortality, longer hospitalization, and more severe disease after COVID-19 infection [3–6]. Recent data have shown that both type 1 diabetes (T1D) and type 2 diabetes (T2D) are independent risk factors for increased mortality with COVID-19 [7]. Further, it is now known that poor glucose control before hospital admission can be associated with a high risk of in-hospital death [8].

With the approval of two mRNA vaccines by Pfizer-BioNTech and Moderna, and of the Johnson & Johnson adenovirus vaccine, there is hope on the horizon that the pandemic is being brought under control. However, genetic variants of the virus have been circulating throughout the pandemic. Variants of concern are classified as those for which there is evidence of an increase in transmissibility [9,10], more severe disease (e.g. increased hospitalizations or deaths), a significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines [11], or diagnostic detection failures. At present, according to the Centers for Disease Control and Prevention, the B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2; AY (Delta), and P.1 (Gamma) variants circulating in the United States are classified as variants of concern [12]. As COVID-19 infection remains a risk despite vaccination, understanding how to optimally manage diabetes is critical to reduce the risk of serious outcomes in the event of contracting COVID-19. However, much of the literature on people with diabetes who contract COVID-19 focuses on hospitalized patients, and advice for primary care physicians (PCPs) is limited. Here, we provide an overview of the evidence linking hyperglycemia and diabetes to poorer outcomes after COVID-19 infection, as well as guidance for PCPs on the management of diabetes to reduce the risk of severe COVID-19 for this population.

2.0. Considerations

2.1. Why does it remain important to consider diabetes and COVID-19?

A recent study from Wuhan [13] showed that nearly 70% of patients with type 2 diabetes and laboratory-confirmed COVID-19 had suboptimal blood glucose control. The authors suggested the following as potential reasons for this: (1) a relative shortage of endocrinologists, leading to delay or absence of professional advice; (2) lack of provision of dietary advice; (3) inability to exercise; 4) anxiety from COVID-19 inducing hyperglycemia; (5) glucose metabolism disorders arising from pancreatic tissue being a potential target of viral infection. Further, the adverse effect of the pandemic manifests in patients living with diabetes delaying seeking care due to concern about contracting COVID-19, leading to missed diagnoses, delays in treatment, and potential undertreatment with poor glucose control [6]. Furthermore, it is now known that the risks of morbidity and mortality for those who survive hospitalization with COVID-19 do not end with hospital discharge, with the serious effects of ‘long-COVID’ or ‘post-COVID syndrome’ becoming more apparent. Results of a recent study in England revealed that of 47,780 people who were discharged from hospital after COVID-19, nearly one-third were readmitted and over 12.3% died after discharge [14]. Rates of diabetes were significantly increased in people with COVID-19, being diagnosed in 4.9% of individuals after discharge – a rate 1.5 times higher than in the matched control group from the general population.

In the reverse scenario, an analysis of data from the Veterans Affairs health system revealed that compared with those who had not been infected with COVID-19, those who survived the disease were approximately 39% more likely to have a diabetes diagnosis in the 6 months after infection [15]. A retrospective analysis of medical records of children newly diagnosed with T2D at Children’s Hospital Los Angeles revealed an increase in new-onset T2D from 44 individuals in 2018 to 82 in 2020 and, worryingly, a significantly (p = 0.029) increased prevalence of diabetic ketoacidosis (DKA) from 9% in 2018 to 20% in 2020 [16]. While none of the patients hospitalized for DKA tested positive for the SARS-CoV-2 antigen by polymerase chain reaction test, six patients were tested for IgG serology, and two were positive.

2.2. Why are people with diabetes at increased risk of poor outcomes with COVID-19?

There are several reasons why individuals with diabetes may be more susceptible to poorer outcomes. The immune function of people with T1D and elevated hemoglobin A1c (HbA1c) is compromised, which makes them particularly susceptible to infectious disease [17]. Significant hyperglycemia occurs in the acute inflammatory state of COVID-19, and is more pronounced in those with diabetes, prediabetes, and/or obesity [18]. In those with T2D and obesity, a change in baseline inflammatory state, including alterations in chemokines and cytokines, may cause a shift to an activation state of leukocytes, increased fibrosis, and apoptosis, which results in further elevations in inflammatory cytokine levels [18]. A study in people with COVID-19 showed that biomarkers for inflammation, including interleukin-6, C-reactive protein, serum ferritin coagulation index, and D-dimer, were significantly higher in those with diabetes compared with those without [19], which could possibly render them more susceptible to the cytokine storm observed in COVID-19. This inflammatory response may also occur in those with diabetes and nonalcoholic fatty liver disease [20], which has been shown to be a risk factor for hospitalization with COVID-19 [21].

As hyperglycemia is linked to immune dysfunction, people with diabetes tend to be at an increased risk of contracting infectious disease and experiencing more serious symptoms [22]. In the case of COVID-19, the angiotensin-converting-enzyme 2 (ACE2) receptor has been identified as the site to which the coronavirus spike protein attaches and uses to enter cells (Figure 1; [23]) [17,24]. In people who are infected with COVID-19, after endocytosis of the virus, expression of ACE2 receptors appears to be downregulated, resulting in increased angiotensin II, and a decrease in the protective effect of the enzyme within the body’s organs, leading to cellular damage and hyperinflammation [25–27]. This cascade of events may be heightened in people with diabetes and/or hyperglycemia. Further, pancreatic β-cells express ACE2, so SARS-CoV-2 could cause β-cell damage, resulting in worsening glucose control in patients with preexisting diabetes, or inducing new-onset diabetes in patients with previous euglycemia [28]. Interestingly, this phenomenon was previously observed when multiple cases of new-onset diabetes were observed in individuals infected with SARS [29]. This remains a hypothesis for SARS-CoV-2, although, as mentioned above, evidence of this effect is becoming more apparent.

Figure 1. Loss of ACE2 action during SARS-CoV-2 infection drives multiple pathologies in multiple organs. ACE2, angiotensin-converting enzyme 2; Ang, angiotensin; AT₁R, angiotensin II type 1 receptor; MasR, Mas receptor, MMP, matrix metalloproteinase; NO, nitrous oxide; ROS, reactive oxygen species; SARS-CoV-2, severe acute respiratory syndrome-coronavirus 2. Figure reproduced with permission from: M. Gheblawi, K. Wang, A. Viveiros, et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system celebrating the 20th anniversary of the discovery of ACE2, Circ. Res. 126 (2020) 1456–1474 [23]. Copyright 2020, Wolters Kluwer Health

2.3. Is there a difference in COVID-19 outcomes in people with type 1 versus type 2 diabetes?

Results of a prospective cohort study from Vanderbilt University Medical Center showed that compared with not having diabetes, both T1D and T2D were associated with increased risk of hospitalization (adjusted odds ratio [OR] [95% CI], 3.90 [1.75–8.69] for T1D and 3.36 [2.49–4.55] for T2D), and greater illness severity (OR [95% confidence interval (CI)], 3.35 [1.53–7.33] for T1D and 3.42 [2.55–4.58] for T2D) [30]. Similarly, a study conducted to assess the risk of in-hospital death due to COVID-19 for individuals registered within general practices in England [7] revealed that after adjusting for demographic factors, the ORs for in-hospital COVID-19–related death were 3.51 (95% CI: 3.16–3.90, p < 0.0001) for T1D and 2.03 (95% CI: 1.97–2.09, p < 0.0001) for T2D [7]. These findings contrast with a study from France with a primary outcome of tracheal intubation or death by Day 7 of hospitalization [31], in which a lower risk for severe prognosis was observed in people with T1D versus T2D (23.2% vs 27.2%) [31]. However, all studies demonstrate that both T1D and T2D are independent risk factors for more severe COVID-19 disease.

2.4. Is the relationship between diabetes and poor COVID-19 outcomes because of diabetes itself, degree of glucose control, or both?

A number of studies have shown that people with diabetes are at increased risk for more severe COVID-19 disease, with hyperglycemia being a key contributory factor [3,5,6,32]. In a retrospective observational study of hospitalized patients with laboratory-confirmed COVID-19, outcomes were assessed for patients with diabetes (HbA1c ≥6.5%) and/or uncontrolled hyperglycemia (>2 blood-glucose readings >180 mg/dL within a 24-hour period, and HbA1c <6.5%) versus those without diabetes or uncontrolled hyperglycemia. Patients with diabetes and/or uncontrolled hyperglycemia had a longer mean hospital stay (6.2 ± 3.7 vs 5.0 ± 3.3 days, p < 0.001) and an almost five-fold higher mortality rate (28.8% vs 6.2%, p < 0.001) compared with those without these conditions [3]. In the subsets of patients with either diabetes (n = 88) or uncontrolled hyperglycemia without diabetes (n = 96), mortality rates were higher in those with hyperglycemia without diabetes (41.7%) than in those with diabetes (14.8%; p < 0.001) [3]. In another study, occurrence of a composite endpoint of severe disease, admission to an intensive care unit, use of mechanical ventilation, or death was assessed according to hyperglycemic or normoglycemic status in 59 patients hospitalized with moderate COVID-19 disease [4]. In that study, both hyperglycemia and diabetes were independent risk factors for worse outcomes with COVID-19. Interestingly, Kaplan–Meier analysis suggested that outcomes were worse in patients with hyperglycemia, with or without diabetes, than in those with diabetes and normoglycemia [4]. Importantly, poor glycemic control before hospitalization, as well as in the inpatient setting, has also been linked to worse COVID-19 outcomes [7,8,32,33]. These findings suggest that poor outcomes with COVID-19 are associated independently with diabetes and hyperglycemia; however, hyperglycemia alone is a higher risk factor than diabetes.

2.5. What is the effect of ACE inhibitor therapy on COVID-19 risk in people with diabetes?

Early during the pandemic, concern was raised that ACE inhibitors may increase the risk of serious outcomes after COVID-19 infection. It was suggested that ACE inhibition would result in an increase in ACE2 receptors, increasing the ability of SARS-CoV-2 to enter the lungs [34]. However, data from a prospective cohort study of 1205 general practices in England revealed that of the 19,486 patients who acquired COVID-19 [35], those who received ACE inhibitors had a reduced risk of requiring hospital admission (adjusted hazard ratio [HR] 0.71, [95% CI: 0.67–0.74]), and no increased risk of needing intensive care (adjusted HR 0.89 [95% CI: 0.75–1.06]) [35]. The results of several other studies concur with these data, demonstrating no increased risk of severe COVID-19 outcomes in patients receiving ACE inhibitors or angiotensin-II receptor blockers [36–41]. Together, these results support the continued standard use of these drugs to treat hypertension and decrease long-term progression of renal disease in patients at high risk of COVID-19.

3.0. The importance of glycemic control in the COVID-19 era and the role of primary care

As reviewed above, diagnosis of hyperglycemia on hospital admission is linked to poorer outcomes with COVID-19, including increased length of hospital stay, severe disease, and death [3–6,32]. However, poor control before hospital admission is also an important factor and can be associated with a high risk of in-hospital death. For example, analysis of the OpenSAFELY cohort revealed that people with diabetes and HbA1c ≥7.5% had an HR for COVID-19 mortality of 2.61 (95% CI: 2.46–2.77) compared with an HR of 1.58 (95% CI: 1.51–1.66) for those with HbA1c <7.5% [33]. Similarly, in a study in England of people with COVID-19 and either T1D or T2D, the risk of death from COVID-19 was found to be significantly higher in those with HbA1c >10% versus 6.5–7%, with ORs (95% CI) of 2.23 (1.50–3.30) for T1D and 1.61 (1.47–1.77) for T2D; both p < 0.0001 [8].

It has long been known that glycemic control is important in slowing the progression of diabetes, as well as reducing the risk of associated complications. The benefits of achieving HbA1c <7% for reducing risk of microvascular complications in T2D are well established [42,43]. Despite this, there is often a delay in therapy intensification; for example, a retrospective cohort study of 105,477 patients from the UK revealed that 22% of patients with newly diagnosed T2D remained under poor glycemic management after 2 years, and 26% never received treatment intensification [44]. Further, in people with T2D inadequately controlled on oral antihyperglycemic agents, intensification to injectable therapy is often delayed until HbA1c levels are considerably above target, when glycemic control is harder to achieve [45]. A real-world study of individuals with HbA1c ≥9% showed that less than 25% are likely to achieve HbA1c <7% with either a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or basal insulin alone [45], suggesting that intensification with combination therapy may be warranted. Indeed, a study that assessed simultaneous versus sequential initiation of basal insulin and a GLP-1 RA in patients with T2D inadequately controlled on oral antihyperglycemic medications demonstrated that simultaneous initiation results in significantly better glycemic control than sequential initiation with a treatment gap of >90 days [46]. Given the benefits of good glycemic control, in terms of both slowing progression of diabetes and its complications and the importance of glycemic control for those with COVID-19, proactive intensification of therapy for optimal glycemic control is crucially important.

3.1. Considerations for use of antihyperglycemic agents in the COVID-19 era

The approach to glycemic control in ambulatory patients with COVID-19 should follow usual management algorithms, with careful attention to appropriate escalation of therapy when blood glucose levels are not at goal. Sick day management should be per usual recommendations, including continuing to take current diabetes medication(s), regular monitoring of blood glucose, staying hydrated, eating normally, and checking body weight and temperature [47].

Although preclinical data have reported an association of several antidiabetic therapy classes – namely insulin, thiazolidinediones, sodium glucose co-transporter 2 (SGLT2) inhibitors GLP-1 RAs – with upregulation of ACE2 expression, increasing the ability of SARS-CoV-2 to enter the lungs [48], as described above, evidence in humans is lacking. Therefore, as the benefits of these drugs outweigh the theoretical risk, therapy should be continued as required. However, there are a number of considerations for the use of antihyperglycemic agents in individuals who have COVID-19 infection (Table 1; [17,49]). For those who test positive for COVID-19 but are asymptomatic, no change in regimen is needed. Patients with mild disease can continue their usual treatment, while being alerted that a change, as described in Table 1, may be needed if the severity of their illness increases. For patients who self-monitor blood glucose and for those receiving insulin, more frequent blood-glucose monitoring may be advised [17]. Results of a meta-analysis showed that metformin use is associated with a significant (p = 0.02) reduction in COVID-19 infection mortality rate (relative risk [95% CI]: 0.54 [0.32–0.90] [50], leading some to recommend that metformin be continued even in those with more severe COVID-19 symptoms [51]. That said, due to the increased risk of lactic acidosis [17], consideration should be given to withhold metformin in people with respiratory distress, renal impairment, or heart failure [49]. Sulfonylureas should be discontinued in those with diabetes and COVID-19 because of the risk of hypoglycemia, particularly if chloroquine is used concurrently [49]. There were concerns that use of SGLT2 inhibitors in those with severe COVID-19 symptoms could increase the risk of acute kidney injury and diabetic ketoacidosis, it was recommended to consider discontinuing SGLT2 inhibitors in these individuals [17]. However, results of the DApagliflozin in REspiratory failure in patients with COVID-19 (DARE-19) study presented at the recent American College of Cardiology meeting have shown that when used in patients hospitalized with COVID-19 who had risk factors for developing serious complications (including high blood pressure, diabetes, atherosclerotic vascular disease, heart failure or chronic kidney disease), dapagliflozin was well-tolerated, with no new safety issues identified. Although the primary endpoint of organ failure or death was not significantly different between dapagliflozin and placebo, the results numerically favored dapagliflozin, rates of serious adverse events were numerically lower with dapagliflozin than placebo, leading the principal investigator, Mikhail Kosiborod, to conclude that ‘the results do not support discontinuation of SGLT2 inhibitors in this setting, as long as patients are monitored.’ [52] Due to the risk of aspiration pneumonia, GLP-1 RAs should be discontinued in patients severely ill with COVID-19 [49]. Cell studies have identified dipeptidyl peptidase-4 (DPP-4) as a functional receptor for human coronavirus-Erasmus Medical Center [53]. As such, inhibition of DPP-4 may be a potential mechanism by which severe symptoms of COVID-19 could be mitigated. This hypothesis is supported by results of a recent observational study of people with T2D who were admitted to the hospital with COVID-19, which showed that those who received sitagliptin at the time of hospitalization had reduced mortality and improved clinical outcomes versus those who received intravenous or subcutaneous insulin [54]. Results of a recently published systematic review [55] suggest that DPP-4 inhibitor use was not associated with an increase in the composite outcome of severe COVID-19 and mortality, likely because ACE2, rather than DPP-4 is the major binding partner for COVID-19. The authors concluded that DPP-4 inhibitors can be used as needed in people with COVID-19 and diabetes.

Table 1. Considerations for the use of antihyperglycemic drugs in patients with diabetes and COVID-19

	Advantages	Disadvantages	Advice
Metformin	No risk of hypoglycemia	Risk of lactic acidosis in case of respiratory distress	Given risk for deterioration, dehydration with subsequent increased risk for lactic acidosis can occur, so consideration should be given to withholding metformin.
		Renal impairment	Follow renal function if warranted.
		Heart failure	In people with diabetes and COVID-19 who have respiratory distress, renal impairment, or heart failure, it is recommended to stop treatment with metformin due to the risk of lactic acidosis.
DPP-4 inhibitors	No risk of hypoglycemia Available for a wide renal function range Potential anti-inflammatory action Potential modification of SARS-CoV-2 binding to DPP-4	N/A	These drugs are generally well tolerated and can be continued.
SGLT2is	No risk of hypoglycemia	Risk of hypovolemia Electrolyte imbalances Euglycemic ketoacidosis	Given risk for deterioration, dehydration with subsequent increased risk for euglycemic diabetic ketoacidosis can occur, so consideration should be given to withholding SGLT2is. Avoid initiating therapy during respiratory illness. Renal function should be monitored when appropriate for acute kidney injury.
GLP-1 RAs	No risk of hypoglycemia Potential anti-inflammatory action	Risk of astrointestinal side-effects and aspiration	Adequate fluid intake and regular meals should be encouraged. GLP-1 RAs may be discontinued in patients severely ill with COVID-19.
Sulfonylureas	N/A	Risk of hypoglycemia if oral intake is administered with other glucose-lowering agents	Given risk for deterioration, sulfonylureas should be with held if patient at risk for hypoglycemia.
Pioglitazone	Anti-inflammatory action	Risk of fluid retention and heart failure	The use of pioglitazone in patients with diabetes COVID-19 is controversial because of the risk of fluid retention and edema in hemodynamically unstable patients.
Insulin	Recommended in critical patients	Risk of hypoglycemia Possible need for high doses Intravenous administration	Recommended in critical patients Insulin therapy may need to be adjusted. Regular self-monitoring of blood glucose, or use of continuous glucose monitoring should be encouraged. Carefully adjust regular therapy, if appropriate, to reach therapeutic goals according to diabetes type, comorbidities, and health status.

Adapted from Bornstein et al. 2020 [17] and Apicella et al. 2020 [49]. DPP-4: dipeptidyl peptidase-4; GLP-1 RA, glucagon-like peptide-1 receptor agonist; N/A, not applicable; SARS-CoV-2, severe acute respiratory syndrome-coronavirus 2; SGLT2i, sodium-glucose-cotransporter 2 inhibitor.

3.2. How should I approach telehealth for my patients with diabetes during the COVID-19 pandemic?

Due to the increased risk of serious disease with COVID-19 in people with diabetes, it is important that patients are well informed on the importance of optimal metabolic and glycemic control. Fears relating to COVID-19 that may lead patients to avoid seeking medical advice should be proactively addressed, particularly for those with uncontrolled blood glucose, a risk factor for severe COVID-19 disease. Antihyperglycemic therapy should be optimized to achieve HbA1c targets while exercising caution regarding premature discontinuation of established therapy [17].

Telehealth has emerged as a valuable service to provide continued medical care while decreasing the potential for exposure to COVID-19. Studies of telemedicine in diabetes management have shown promising results [56]; as well as being used to provide care, telehealth visits can also be used to provide advice and education on exercise, diet, changes in therapy, and self-monitoring of blood glucose and blood pressure. Telemedicine has also been shown to be effective in helping lower HbA1c, as well as empowering patients [57,58]. A recent US claims database study has shown that there was a 100-fold increase in use of telehealth from 2019 (0.3%) to 2020 (29.1%), with the authors noting that this increased use did not negatively impact medication fills or glycemic control [59]. Exposure to COVID-19 can also be reduced by online prescription delivery systems, which have been shown to be successful in a number of studies from China [60,61].

Decisions regarding face-to-face visits versus telehealth appointments will be driven by local COVID-19 infection rates and patient factors. Cumulative risk is another factor to consider. For instance, five face-to-face visits would present more risk than one face-to-face visit followed by four telehealth checkups. For patients who find telemedicine difficult, a face-to-face checkup may be worthwhile.

3.3. Tips for timely and effective initiation of injectable therapy during the COVID-19 pandemic

For those who need it, providing timely treatment intensification to injectable therapy during the COVID-19 pandemic may necessitate the use of telemedicine. It has already been shown that telehealth monitoring can improve support for people with T2D initiating insulin [58]; and in patients with T1D receiving insulin therapy with a subcutaneous pump, telehealth has been used to successfully lower HbA1C with no increase in diabetic ketoacidosis events despite no in-office visits for 6 months [62].

The most important factor is to identify patients who need to start injectable therapy. It is vital that the limiting factor on moving forward with intensification is not that the consultation may have to be virtual. It is possible to teach injection technique virtually by inviting the patient to watch demonstration videos, either alone or with the healthcare provider. Some people will need further help, and in these cases, a visit by a nurse or certified diabetes educator can be scheduled. Once the patient is comfortable with self-injection, any dose adjustment could be managed in conjunction with the patient self-monitoring their glucose levels or by continuous glucose monitoring.

4.0. Conclusions

The availability of several SARS-CoV-2 vaccines has provided hope that high COVID-19 infection rates will be brought under control in the coming months. However, with concerns over new variants and overwhelmed healthcare systems, it remains vitally important to preserve the health of those who are most at risk of severe COVID-19 disease. Further, despite encouraging initial reports of the effectiveness of vaccines in older adults [55], the effectiveness in those with diabetes who may have compromised immune systems remains to be seen; indeed, the use of booster vaccines in immunocompromised individuals has just been approved in the US, although at present, only transplant patients and those undergoing therapies for cancer have been specifically mentioned. Because of the threat that COVID-19 poses to people with hyperglycemia and diabetes, the need for effective management in the outpatient setting is paramount, and the role of the PCP in limiting the risk of severe COVID-19 disease through effective management of blood glucose is crucial. PCP confidence in vaccines is important, both in personal receipt of the injection, as well as in positive communication with patients, particularly as rates of uptake have slowed because of the perceived risk of blood clots with adenovirus-type vaccines. Patient education on the importance of metabolic and glycemic control is more important than ever, and in those in whom it is necessary, intensification to injectable therapies (e.g. insulin or combination therapies) should be prioritized. Telemedicine can and should be used to reach patients when risk of COVID-19 exposure is high but does require providers to consider new ways of appropriately intensifying treatment, which can be particularly challenging with injectable therapies. Telemedicine use should be guided by the local COVID-19 environment, notwithstanding that it is reasonable to have a face-to-face meeting if the benefit is considered greater than the risk.

Author contributions

Both authors contributed to the manuscript concept, critically reviewed and revised the drafts and reviewed and approved of the final draft. Both authors are accountable for the content of this manuscript.

Acknowledgments

The authors received writing and editorial support in the preparation of this manuscript, provided by Barrie Anthony and Helen Jones of Evidence Scientific Solutions, and funded by Sanofi US.

Disclosure statement

JP reports that he has served as a consultant for Diasome, Lexicon, Mannkind, Novo Nordisk, and Sanofi.

NS reports nonfinancial support from AstraZeneca, Boehringer Ingelheim, Sanofi, Bayer, and GlaxoSmithKline (GSK); personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and GSK; and serving on advisory boards of AstraZeneca, Boehringer Ingelheim, Teva Pharmaceutical, Eli Lilly, Sanofi, Sanofi Pasteur, GSK, and Bayer.

A reviewer on this manuscript has disclosed that in the past (until 2017) they have received honoraria and travel grants and have served on advisory boards for Novo Nordisk, Eli Lilly, Ethicon, Pfizer Inc., Sanofi-Aventis, AstraZeneca, Merck-Serono, Boehringer Ingelheim, Janssen, and Novartis. The other peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

Writing support for this manuscript was funded by Sanofi US.