Penn State Study Shows That Glucose-Regulating Drugs Like GLP-1R Agonists, DPP-4 Inhibitors & Pioglitazone Reduces Risk Of COVID-19 Severity

COVID-19 Drugs: A new multinational retrospective cohort study by researchers from Penn State College of Medicine, Pennsylvania-USA shows that glucose-regulating medications used to treat obesity and type-2 diabetes may improve outcomes in COVID-19 patients with type-2 diabetes.

It has already been known that individuals with type 2 diabetes mellitus (T2DM) are at increased risk of severe COVID-19 outcomes possibly due to dysregulated inflammatory responses.
 
The study findings showed that glucose-regulating medications such as glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and pioglitazone are known to have anti-inflammatory effects that may improve outcomes in patients with SARS-CoV-2 infection.
 
The study team in a multinational retrospective cohort study used the TriNetX COVID-19 Research Network of 56 large healthcare organizations to examine these medications in relation to the incidence of hospital admissions, respiratory complications, and mortality within 28 days following a COVID-19 diagnosis.
 
After matching for age, sex, race, ethnicity, body mass index, and significant comorbidities, use of GLP-1R agonists and/or pioglitazone was associated with significant reductions in hospital admissions (GLP-1R: 15.7% vs 23.5%; RR, 0.67 [95% CI, 0.57-0.79]; P <.001; pioglitazone: 20.0% vs 28.2%; RR, 0.71 [95% CI, 0.54-0.93]; P =.01). Use of GLP-1R agonists was also associated with reductions in respiratory complications (15.3% vs 24.9%; RR, 0.62 [95% CI, 0.52-0.73]; P <.001) and incidence of mortality (1.9% vs 3.3%; RR, 0.58 [95% CI, 0.35-0.97]; P =.04). Use of DPP-4 inhibitors was associated with a reduction in respiratory complications (24.0% vs 29.2%; RR, 0.82 [95% CI, 0.74-0.90]; P <.001), and continued use of DPP-4 inhibitors after hospitalization was associated with a decrease in mortality compared with those who discontinued use (9% vs 19%; RR, 0.45 [95% CI, 0.28-0.72]; P <.001).
 
The study findings concluded that use of glucose-regulating medications such as GLP-1R agonists, DPP-4 inhibitors, or pioglitazone may improve outcomes for COVID-19 patients with T2DM.
 
The study team also suggest further randomized clinical trials to assess and validate this study findings.
 
The study findings were published in the peer reviewed journal: Diabetes (A journal of the American Diabetes Association.) https://diabetes.diabetesjournals.org/content/early/2021/10/04/db21-0385
 
Senior author Dr Patricia Sue Grigson of Penn State College of Medicine in Hershey, Pennsylvania told Thailand Medical News, "The most important finding of this study for clinicians is the highly protective effect of glucagon-like peptide-1 receptor (GLP-1R) agonist treatment against mortality in patients with type 2 diabetes mellitus (T2DM)."
 
She further added, "Given this finding, and the safe profile of these medications, the data suggest that GLP-1 agonists should be given strong consideration as a treatment strategy for this vulnerable patient population.”
 
Dr Sue Grigson a nd her Penn State team analyzed the electronic medical records of almost 30,000 de-identified patients treated at 56 healthcare organizations, mainly in the United States.
 
Most of the patients had type-2 diabetes and had tested positive for SARS-CoV-2 between January and September 2020.
 
The COVID-19 Drugs study team investigated whether patients who were taking GLP-1R agonists, other diabetes medications, or both, six months or less before being diagnosed with COVID-19 had better outcomes than almost 24,000 similar patients who were not taking these medications.
 
The study findings showed that there were significantly fewer hospital admissions among patients taking versus not taking GLP-1R agonists (15.7% vs. 23.5%; risk ratio, 0.67; P<0.001) and pioglitazone (20.0% vs. 28.2%; RR, 0.71; P=0.01). Treatment with GLP-1R agonists was also linked with fewer respiratory complications (15.3% vs. 24.9%; RR, 0.62; P<0.001) and decreased mortality (1.9% vs. 3.3%; RR, 0.58; P=0.04).
 
Also, treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors was linked with fewer respiratory complications (24.0% vs. 29.2%; RR, 0.82; P<0.001).
 
Importantly patients who continued to use DPP-4 inhibitors after hospitalization had fewer deaths than those who discontinued their use (9% vs. 19%; RR, 0.45; P<0.001).
 
The usage of the drug Pioglitazone also showed decreased risk of hospital admission, but neither DPP-4 nor pioglitazone showed decreased risk of death.
 
Dr Sue Grigson further explained, "It was important to conduct this study because patients with T2DM are at very high risk of death from COVID-19. As such, it is critical that we identify treatment strategies that may be protective.”
 
She added, “Although this retrospective study cannot show cause and effect," she added, the study results suggest that treatment of patients with T2DM with GLP-1R agonists will lead to greater resilience and greater survival following a diagnosis with COVID-19."
 
Dr Nazia T. Raja-Khan, co-lead author who is also from Penn State College of Medicine however cautioned, "We looked at the use of GLP-1R agonists within six months prior to COVID-19 diagnosis, not their initiation at the time of COVID-19 diagnosis. There is no evidence that starting GLP-1R agonist treatment for the first time during the acute management of COVID-19 is safe or effective."
 
Dr Jennifer E. Nyland, co-lead author noted that using a worldwide database that is continuously being updated is a weakness and an asset.
 
She said, "The research is constantly evolving at a rapid rate.”
 
She also added that observed that the study findings "leave a plethora of unanswered questions such as, 'How does duration of treatment or duration of disease affect outcomes?'"
 
Dr Nyland commented, "With this ever-changing landscape, it's impressive how the medical and research communities have come together and eliminated barriers to save lives."
 
The study team concluded, “These study findings suggest that treatment with GLP-1R agonists prior to hospitalization, and DPP-4 inhibitors prior to and/or during hospitalization may be expedient interventions to reduce mortality in patients with COVID-19 and T2DM. This hypothesis warrants further evaluation to determine whether the suggestion of a protective effect bears out in a prospective observational study or adequately powered randomized clinical trial. Subsequent assessment also should consider whether prolonged use is necessary or whether benefit can be derived from acute administration. The DPP-4 data are particularly interesting in this regard. Clinical trials also could be considered in patients without T2DM and across the lifespan to determine whether these agents possess intrinsic protective properties that could represent a novel therapeutic approach against SARS-CoV-2 infection.”

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