Metformin reduces the risk of severe COVID-19 disease in diabetics

Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an urgent global public health crisis.

During the pandemic, those with chronic conditions such as diabetes are often at increased risk of developing severe COVID-19. In fact, several inflammatory markers have been observed in diabetics, suggesting that this disease may be a risk factor in the progression and prognosis of COVID-19.

To learn: Antidiabetic treatment and COVID-19 outcomes: a population-based cohort study in primary health care in Catalonia during the first wave of the pandemic. Image credit: LeviMax /


Several mechanisms that may increase the severity and risk of COVID-19 include reduced CD4+ T cells and increased expression of the host’s angiotensin-2 converting enzyme (ACE2) receptor and interleukin 6 (IL -6). Dipeptidyl peptidase 4 (DPP4) interaction may also promote virulence of SARS-CoV-2, with inhibition of this interaction shown to reduce COVID-19-associated inflammatory storm.

DPP4 inhibitors (iDPP4) are hypoglycemic agents that are highly selective and may increase glucagon-like peptide-1 (GLP1) bioavailability and have immunoregulatory and anti-inflammatory effects. Therefore, iDPP4 has the potential to effectively prevent fatal outcomes associated with COVID-19 and improve outcomes in diabetics.

Metformin, another antidiabetic, is said to have an anti-inflammatory effect. In fact, reduced mortality has been observed after treatment with metformin in high-risk diabetics with COVID-19.

Few other oral antidiabetics have been observed to bind to SARS-CoV-2 receptors and inhibit transcription and replication of the virus. GLP1 analogues could also be used to treat COVID-19 due to their anti-obesity, anti-inflammatory and lung-protective effects.

Previous studies have shown an association between higher mortality and poor glycemic control in COVID-19 patients with diabetes. However, no guidelines have been developed specifically targeting the treatment of COVID-19 in diabetics.

A new Primary care diabetes Study determines if antidiabetic drugs can reduce complications in COVID-19 patients with diabetes by assessing mortality rates and hospital admissions in Catalonia, Spain.

About the study

The current study included adult patients diagnosed with COVID-19 between March 2020 and June 30, 2020. The data was collected using the Information System for Research in Primary Care (SIDIAP), which includes clinical information from around 5.8 million people from Catalonia. Spain.

Data were collected on sociodemographics, long-term care facility (LTCF), toxic habits, clinical parameters, date of hospital admission, laboratory testing, drug prescriptions, comorbidity, pharmacy bill, COVID-19 diagnosis, and discharge.

Confirmed cases included patients with a confirmed COVID-19 diagnosis report, while possible or equivocal cases included those with an unconfirmed diagnosis but a record of COVID-19-related pneumonia, hospitalization, and/or death.

Patients were classified as being exposed to metformin or other antidiabetic drugs if a prescription was issued six months before their COVID-19 diagnosis, along with a minimum duration of 30 days. Those not meeting this criterion were classified as untreated.

The reference group included people exposed to metformin monotherapy. Other antidiabetic drugs included insulin, iDPP4, sulfonylureas, GLP1, sodium glucose co-transporter 2 inhibitors (iSGLT2), and other hypoglycemic agents.

Information on multiple variables was collected at baseline and included gender, body mass index (BMI), age, smoking habit, LTCF, glycated hemoglobin (HbA1c) measured up to six months prior to diagnosis of COVID-19, comorbidities, drug exposure, and years since being diagnosed with type 2 diabetes.

Primary severity endpoints, including mortality and hospital admission rate, were compared between patients exposed to metformin and those not receiving metformin but receiving other antidiabetic medicinal products.

study results

The study involved a total of 31,006 people previously diagnosed with type 2 diabetes and infected with SARS-CoV-2. Among them, 21,131 received antidiabetic treatment, while 13,549 were exposed to metformin. The mean age of the patients was 71.5 years, with 50.9% being current smokers.

The most commonly reported comorbidities included obesity, hypertension, and respiratory disease, while the most commonly prescribed co-medications included ACE inhibitors, nonsteroidal anti-inflammatory drugs, and psychiatric drugs.

About 57% of antidiabetic drug users received metformin alone, while the most commonly used pharmacological groups included iDPP4, insulin and metformin. Hospitalization was reported in 5,096 patients and death was reported in 4,678 patients.

Patients treated with insulin alone, insulin in combination with metformin, or iDPP4 alone were more likely to develop serious outcomes compared to metformin alone. Less common combinations, which were also associated with a higher risk of serious outcomes, were metformin, sulfonylureas, iDPP4, or insulin, and other antidiabetic drugs.

Patients receiving insulin or insulin with metformin also had a higher risk of death compared to metformin monotherapy. Other less common combinations that showed a higher risk of mortality were insulin with GLP1, and insulin, metformin, and sulfonylurea.


Diabetics infected with SARS-CoV-2 had a lower risk of hospitalization and death with metformin monotherapy than with other antidiabetic treatments. More research is needed to determine if better outcomes are associated with metabolic controls or other interventions used during hospitalization.


In the current study it was not established whether only adherent patients can lead to the same or different results. In addition, study results were associated with greater metabolic control than antidiabetic therapy.

In addition, the COVID-19 diagnosis was not entirely reliable. A final limitation was that the study could not capture interventions or treatments delivered during hospital admission, ventilation, and ICU admission.

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