Spanish Study Shows That Metformin (Glucophage) Lowers Risk Of Disease Severity And Fatal Outcomes In Diabetic Patients Infected With COVID-19

COVID-19 Drugs: Spanish researchers and physicians have in a new study found that the diabetic drug Metformin (Glucophage) lowers the risk of disease severity and fatal outcomes in diabetic patients infected with the SARS-CoV-2 coronavirus.

The study involved medical researchers from the Hospital Clinic of Barcelona-Spain, Universitat Autònoma de Barcelona-Spain and Fundació Institut Universitari per a la Recerca a l′Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)-Spain.
 
The COVID-19 Drugs study team aimed to analyze if antidiabetic treatments were associated with better COVID-19 outcomes in type 2 diabetic patients, measured by hospital admission and mortality rates as severe outcomes.
 
The study team conducted a cohort study including COVID-19 patients registered in the Primary Care electronic records, in March-June 2020, comparing exposed to metformin in monotherapy with exposed to any other antidiabetic. Data source: SIDIAP (Information System for Research in Primary Care), which captures clinical information of 5,8 million people from Catalonia, Spain.
 
The study team included 31,006 diabetic patients infected with COVID-19, 43.7% previously exposed to metformin, of which 45.5% of them were in monotherapy.
 
The study findings showed that 16.4% were admitted to hospital and 15.1% died. Users of insulin in monotherapy (OR 1.29, 95% CI 1.11–1.50), combined with metformin (OR 1.38, 1.13–1.69) or IDPP4 alone (OR 1.29, 1.03–1.63) had higher risk of severe outcomes than those in metformin monotherapy. Users of any insulin (OR 1.61, 1.32–1.97) or combined with metformin (OR 1.69, 1.30–2.20) had a higher risk of mortality.
 
The study findings showed that patients receiving metformin monotherapy in the study showed a lower risk of hospitalization and death in comparison to those treated with other frequent antidiabetic agents.
 
The study team did note that they cannot distinguish if better outcomes are related with the antidiabetic therapy or with other factors, such as metabolic control or interventions applied during the hospital admission.
 
The study findings were published in the peer reviewed journal: Primary Care Diabetes.
https://www.primary-care-diabetes.com/article/S1751-9918(22)00167-X/fulltext
 
The COVID-19 disease remains an urgent global public health crisis especially with the vast number of new SARS-CoV-2 variants and sub-lineages emerging and the coming late Fall and Winter of 2022 surges expected to be catastrophic.
 
It was found that throughout the pandemic, individuals with chronic conditions, such as diabetes, are often at an increased risk of severe COVID-19. In fact, several inflammatory markers have been observed in diabetic patients, thus suggesting that this disease could be a risk factor for the progression and prognosis of COVID-19.
 
Researchers and clinicians have found that various mechanisms that can increase the severity and risk of COVID-19 including reduced CD4+ T-cells and the increased expression of the host angiotensin-2 converting enzyme (ACE2) rec eptor and interleukin 6 (IL-6).
 
Furthermore, the interaction of dipeptidyl peptidase 4 (DPP4) can also promote the virulence of SARS-CoV-2, with inhibition of this interaction shown to reduce the COVID-19-associated inflammatory storm.
 
Interestingly, DPP4 inhibitors (iDPP4) are hypoglycaemic agents that are highly selective and can increase the bioavailability of the glucagon-like peptide-1 (GLP1), as well as have immunoregulatory and anti-inflammatory effects. Thus, iDPP4 has the potential to be effective in preventing fatal outcomes associated with COVID-19 and improving outcomes in diabetic patients.
 
The antidiabetic drug, Metformin has been reported to possess anti-inflammatory activity. In fact, reduced mortality has been observed following treatment with metformin among high-risk diabetic COVID-19 patients.
https://www.thailandmedical.news/news/university-of-minnesota-led-phase-three-randomized-clinical-trial-shows-that-metformin-reduces-risk-of-covid-19-disease-severity-and-mortality-
 
https://www.thailandmedical.news/news/covid-19-drugs-university-of-alabama-study-shows-that-metformin-decreases-mortality-rate-in-type-2-diabetes-patients-contracting-covid-19
 
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
 
It was also found that a few other oral antidiabetic agents have been observed to bind to SARS-CoV-2 receptors and inhibit the transcription and replication of the virus. GLP1 analogs could also be used for the treatment of COVID-19 due to their anti-obesogenic, anti-inflammatory, and pulmonary protective effects.
 
Numerous past studies have indicated an association of higher mortality with poor control of blood glucose levels in COVID-19 patients with diabetes. However, no guidelines have been devised to specifically target the treatment of COVID-19 in diabetic patients.
 
The present study included adult patients who were diagnosed with COVID-19 between March 2020 and June 30, 2020. Data was collected using the Information System for Research in Primary Care (SIDIAP), which comprises clinical information of about 5.8 million people from Catalonia, Spain.
 
For the study, data on socio-demographic characteristics, long-term care facilities (LTCF), toxic habits, clinical parameters, date of hospital admission, laboratory tests, drug prescriptions, comorbidity, pharmacy invoice, COVID-19 diagnosis, and discharge were collected. Confirmed cases included patients with a confirmed COVID-19 diagnostic report, whereas possible or unclear cases included those with a non-confirmed diagnosis but a record of COVID-19-related pneumonia, hospitalization, and/or death.
 
All study participants were classified as being exposed to metformin or other antidiabetics if a prescription was issued six months before their COVID-19 diagnosis, along with a minimum duration of 30 days. Those who did not meet this criterion were classified as untreated.
 
The study’s reference group comprised people who were exposed to metformin monotherapy. Other antidiabetic agents included insulin, iDPP4, sulfonylureas, GLP1, sodium-glucose co-transporter 2 inhibitors (iSGLT2), and other hypoglycemic agents.
 
Data on several variables was captured at baseline and included sex, body mass index (BMI), age, smoking habit, LTCF, glycated hemoglobin (HbA1c) measured until six months before the diagnosis of COVID-19, comorbidities, drug exposure, and years since diagnosis of type 2 diabetes.
 
The study’s primary severity outcomes involving mortality and rate of hospital admission were compared between patients exposed to metformin and those not exposed to metformin but exposed to other antidiabetics.
 
The research included a total of 31,006 individuals who were previously diagnosed with type 2 diabetes and infected with SARS-CoV-2. Among them, 21,131 received treatment with antidiabetic drugs, while 13,549 were exposed to metformin. The mean age of the patients was 71.5 years, with 50.9% being current smokers.
 
In the study cohort, the most frequently reported comorbidities included obesity, hypertension, and respiratory diseases, while the most prescribed comedications included ACE inhibitors, non-steroidal anti-inflammatory drugs, and psychotropic drugs.
 
In all, about 57% of antidiabetic drug users received metformin alone, while the most used pharmacological groups included iDPP4, insulin, and metformin.
 
The study found that hospitalization was reported in 5,096 patients, with death reported in 4,678 patients.
 
It was found that patients treated with insulin alone, insulin in combination with metformin, or iDPP4 alone were more likely to experience severe outcomes as compared to metformin monotherapy.
 
The study team also observed that less common combinations that were also associated with a higher risk of severe outcomes included metformin, sulfonylureas, iDPP4, or insulin, along with other hypoglycaemic drugs.
 
Also, patients receiving insulin or insulin with metformin were also at a higher risk of mortality as compared to metformin monotherapy. Other less common combinations that showed a higher risk of mortality included insulin with GLP1, as well as insulin, metformin, and sulfonylurea.
 
The study findings clearly showed that diabetic patients infected with SARS-CoV-2, when treated with metformin in monotherapy, had a lower risk of hospitalization and death than with other antidiabetic treatments. Further research is needed to determine if better outcomes are associated with metabolic controls or other interventions that are applied during hospitalizations.
 
One of the limitations of the study was that it did not determine whether only adherent patients could give rise to the same or different results. Furthermore, the study results were associated with a greater degree of metabolic control than antidiabetic therapy.
 
Furthermore, the COVID-19 diagnosis was not completely reliable. A final limitation was that the study was unable to capture interventions or treatments administered during hospital admission, ventilation, and intensive care unit admission.
 
For the latest on COVID-19 Drugs, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/diabetic-patients-taking-sglt2-inhibitors-may-develop-complications-upon-contracting-covid-19-warns-researchers-metformin-is-a-better-option

Note: Do not attempt to self-presribe to prevent or treat COVID-19 or consume any drugs including metformin without consulting a licensed medical doctor first.