Diabetic Patients Taking SGLT2 Inhibitors May Develop Complications Upon Contracting COVID-19 Warns Researchers. Metformin Is A Better Option

Metformin-COVID-19: The American Association of Clinical Endocrinologists in a recent published clinical case report warns that diabetes patients taking SGLT2 Inhibitors to manage their diabetes may develop rare and sometimes serious complications upon contracting COVID-19.


 
SGLT2 inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. Medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, and empagliflozin.
 
Diabetes mellitus is associated with poor outcomes in SARS-CoV-2 infection. Diabetic ketoacidosis (DKA) has also been reported to occur with this virus. A cluster of cases of euglycemic DKA (euDKA) was identified in patients with type 2 diabetes mellitus (T2DM) using SGLT2 inhibitors (SGLT2i) who developed SARS-CoV-2 infection.
 
The cases were identified by the authors while providing clinical care, and details were collected.
 
Five cases of euDKA, with presenting glucose more than 300 mg/dL, were identified over the course of two months on the Endocrinology consult service. All patients had a history of T2DM with no known history of DKA. All were taking SGLT2i. Oral anti-hyperglycemic medications were stopped for all patients on admission. All received intravenous insulin infusion to treat DKA before being transitioned to a subcutaneous insulin regimen. SGLT2i use was discontinued for all patients who were discharged.
 
EuDKA has been seen in the setting of acute illness in patients using SGLT2i, but this cluster of cases suggests there may be a specific association with SARS-CoV-2 infection. In addition to the known risk of euDKA with SGLT2i use, COVID-19-specific mechanisms may include direct toxic effect of the virus on pancreatic islets, accelerated inflammatory response promoting ketosis, and the diuretic effect of SGLT2i in conjunction with anorexia and vomiting. It is crucial to counsel patients to stop SGLT2i when sick, especially if SARS-CoV-2 infection is suspected.
 
The case reports were reported by researchers from Harvard’s Brigham and Women's Hospital and were published in the peer reviewed Journal of the American Association of Clinical Endocrinologists Clinical Case Reports by Elsevier. https://www.aaceclinicalcasereports.com/article/S2376-0605(20)31020-8/pdf
 
Already diabetes is a known risk factor for morbidity and mortality related to COVID-19. In diabetes patients, rare but severe complications, like the potentially lethal condition diabetic ketoacidosis (DKA), can arise when illness or certain conditions prevent cells from receiving enough glucose to fuel their functioning.
 
However an uptick in a particular type of DKA called euDKA at Brigham and Women's Hospital during the COVID-19 pandemic has led researchers to hypothesize that diabetes patients on glucose-lowering drugs may be at increased risk for euDKA when they contract COVID-19.
 
Euglycemic Diabetic Ketoacidosis or EuDKA is a subset of the diabetes complication known as DKA, which occurs when the body's cells fail to absorb enough glucose and compensate by metabolizing fats instead, creating a build-up of acid s called ketones.
 
EuDKA differs from DKA in that it is characterized by lower blood sugar levels, making it more difficult to diagnose.
 
The U.S. Food and Drug Administration has warned that the risk of DKA and euDKA may be increased for individuals who use a popular class of diabetes drugs called sodium-glucose co-transporter 2 inhibitors (SGLT2i), which function by releasing excess glucose in the urine.
 
Underlying nearly all euDKA cases is a state of starvation that can be triggered by illnesses that cause vomiting, diarrhea, and loss of appetite and can be compounded by the diuretic effect of SGLT2i drugs.
 
The Brigham study team studied five unusual euDKA cases brought to the diabetes inpatient services within the span of two months, three of which occurred in one week, at the height of the pandemic in Boston in the spring of 2020.
 
Interestingly the five cases represented a markedly heightened incidence of euDKA compared to that of the previous two years, when inpatient services saw fewer than 10 euDKA cases.
 
Importantly all five of the recent euDKA cases were observed in COVID-19 patients who were taking SGLT2i; three patients were discharged to rehabilitation facilities, one was discharged home, and one, a 52-year-old male with acute respiratory distress syndrome, died.
 
Corresponding author Dr Naomi Fisher of the Division of Endocrinology, Diabetes, and Hypertension at Brigham and Women's Hospital told Thailand Medical News, "We have the background knowledge of recognizing that SGLT2 inhibitors can cause DKA and euDKA. Our report reinforces that if patients are ill or have loss of appetite or are fasting, they should pause their medication and not resume until they are well and eating properly."
 
The study team also suspects that COVID-19 may particularly exacerbate euDKA risks.
 
When the virus infects a patient, it binds to cells on the pancreas that produce insulin and may exert a toxic effect on them. Studies of the earlier SARS-CoV-1 virus found that many infected patients had increased blood sugar.
 
Dr Fisher added, "It's been posited through other models that the virus may be preferentially destroying insulin-producing cells."
 
Furthermore the maladaptive inflammatory response associated with COVID-19, which produces high levels of immune-response-related proteins called cytokines, may increase DKA risks.
 
Dr Fisher added, "These high levels of cytokines are also seen in DKA, so these inflammatory pathways may be interacting. It's speculative, but there may be some synergy between them."
 
Although these study findings are observational, rather than the results of a randomized controlled trial, similar reports of heightened euDKA incidence have emerged from other institutions.
 
The study team encourages patients and physicians to halt SGLT2i-use in the event of illness, which is already standard practice for the most common diabetes drug, metformin.
 
Dr Fisher added, "Patients should continue to monitor their blood sugar, and if the illness is prolonged or if their blood sugar is very high, they can speak to their doctor about other forms of therapy. But often it's a very short course off of the drug. We're hopeful that with widespread patient and physician education, we will not see another cluster of euDKA cases amid the next surge in COVID-19 infections."
 
Interestingly, there were some studies that showed that metformin also benefitted certain COVID-19 patients in other ways as well especially women.
 
https://www.thailandmedical.news/news/latest-medical-news-reports-that-metformin-can-drastically-reduce-covid-19-mortality-risks-in-women
 
https://www.thailandmedical.news/news/breaking-metformin-might-emerge-as-another-covid-19-drug-candidate-with-university-of-minnesota-now-receiving-funding-for-further-research
 
https://www.thailandmedical.news/news/metformin-university-of-minnesota-researchers-discover-that-metformin-may-lower-risk-of-covid-19-deaths-in-obese-and-or-diabetic-women

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