Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Narayanan, Niya; Naik, Dukhabandhu; Sahoo, Jayaprakash; Kamalanathan, Sadishkumar

doi:10.5501/wjv.v11.i6.399

Cited by 5 publications

(5 citation statements)

References 64 publications

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“…DPP-4i, which was chosen as a comparator, also has hypothesized immunomodulatory qualities that solicited attention as a potential COVID-19 therapeutic [ 25 ]. Yet, the results of observational studies of DPP-4i-related impact on COVID-19 have been inconclusive.…”

Section: Discussionmentioning

confidence: 99%

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity

Klein,

Abrahamsen,

Kahkoska

et al. 2024

Diabetes Ther

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Introduction People with type 2 diabetes are at heightened risk for severe outcomes related to COVID-19 infection, including hospitalization, intensive care unit admission, and mortality. This study was designed to examine the impact of premorbid use of glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy, sodium-glucose cotransporter-2 inhibitor (SGLT-2i) monotherapy, and concomitant GLP1-RA/SGLT-2i therapy on the severity of outcomes in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Utilizing observational data from the National COVID Cohort Collaborative through September 2022, we compared outcomes in 78,806 individuals with a prescription of GLP-1RA and SGLT-2i versus a prescription of dipeptidyl peptidase 4 inhibitors (DPP-4i) within 24 months of a positive SARS-CoV-2 PCR test. We also compared concomitant GLP-1RA/SGLT-2i therapy to GLP-1RA and SGLT-2i monotherapy. The primary outcome was 60-day mortality, measured from the positive test date. Secondary outcomes included emergency room (ER) visits, hospitalization, and mechanical ventilation within 14 days. Using a super learner approach and accounting for baseline characteristics, associations were quantified with odds ratios (OR) estimated with targeted maximum likelihood estimation (TMLE). Results Use of GLP-1RA (OR 0.64, 95% confidence interval [CI] 0.56–0.72) and SGLT-2i (OR 0.62, 95% CI 0.57–0.68) were associated with lower odds of 60-day mortality compared to DPP-4i use. Additionally, the OR of ER visits and hospitalizations were similarly reduced with GLP1-RA and SGLT-2i use. Concomitant GLP-1RA/SGLT-2i use showed similar odds of 60-day mortality when compared to GLP-1RA or SGLT-2i use alone (OR 0.92, 95% CI 0.81–1.05 and OR 0.88, 95% CI 0.76–1.01, respectively). However, lower OR of all secondary outcomes were associated with concomitant GLP-1RA/SGLT-2i use when compared to SGLT-2i use alone. Conclusion Among adults who tested positive for SARS-CoV-2, premorbid use of either GLP-1RA or SGLT-2i is associated with lower odds of mortality compared to DPP-4i. Furthermore, concomitant use of GLP-1RA and SGLT-2i is linked to lower odds of other severe COVID-19 outcomes, including ER visits, hospitalizations, and mechanical ventilation, compared to SGLT-2i use alone. Graphical abstract available for this article. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s13300-024-01562-1.

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Section: Discussionmentioning

confidence: 99%

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity

Klein,

Abrahamsen,

Kahkoska

et al. 2024

Diabetes Ther

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“…Our multivariate regression models showed DPP-4 inhibitors were associated with statistically non-significant decrease in odds for COVID-19 death (OR 0.761; 95% CI 0.568–1.019). Some studies have shown DPP-4 inhibitors mortality benefits in diabetic patients with COVID-19 [ 54 ]. DPP-4 inhibitors might inhibit entry of the virus, inhibit inflammation and fibrosis [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have shown DPP-4 inhibitors mortality benefits in diabetic patients with COVID-19 [ 54 ]. DPP-4 inhibitors might inhibit entry of the virus, inhibit inflammation and fibrosis [ 54 ]. However, several studies have shown negative associations in terms of increased mortality risk and intensive care unit (ICU) admission risk for people who use them [ 27 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis

Dimnjaković,

Buble,

Ivanko

et al. 2024

PLoS ONE

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Introduction Patients with diabetes mellitus type 2 and chronic kidney disease (T2DM-CKD) have a 5 times higher risk of developing severe SARS-CoV-2 infection than those without these 2 diseases. The goal of this study is to provide information on T2DM-CKD and COVID-19 outcomes, with an emphasis on the association with anti-diabetic medications. Methodology Study is designed as a retrospective cohort analysis covering the years 2020 and 2021. Data from the National Diabetes Registry (CroDiab) were linked to hospital data, primary healthcare data, Causes of Death Registry data, the SARS-CoV-2 vaccination database, and the SARS-CoV-2 test results database. Study outcomes were cumulative incidence of SARS-CoV-2 positivity, COVID-19 hospitalizations, and COVID-19 deaths. For outcome predictors, logistic regression models were developed. Results Of 231 796 patients with diabetes mellitus type 2 in the database, 7 539 were T2DM-CKD (3.25%). The 2-year cumulative incidences of all three studies’ outcomes were higher in T2DM-CKD than in diabetes patients without CKD (positivity 18.1% vs. 14.4%; hospitalization 9.7% vs. 4.2%; death 3.3% vs. 1.1%, all p<0.001). For COVID-19 hospitalization, protective factors were SGLT-2 inhibitors use (OR 0.430; 95%CI 0.257–0.719) and metformin use (OR 0.769; 95% CI 0.643–0.920), risk factors were insulin use (1.411; 95%CI 1.167–1.706) and sulfonylureas use (OR 1.226; 95% CI 1.027–1.464). For SARS-CoV-2 positivity protective factors were SGLT-2 inhibitors (0.607; 95% CI 0.448–0.823), repaglinide use (OR 0.765; 95% CI 0.593–0.986) and metformin use (OR 0.857; 95% CI 0.770–0.994). DPP-4 inhibitors showed a non-significant decrease in risk for COVID-19 death (OR 0.761; 95% CI 0.568–1.019). Conclusion T2DM-CKD are heavily burdened by COVID-19 disease. Our results suggest no association between antidiabetic drugs and COVID-19 death outcome while SGLT-2 and metformin show to be protective against COVID-19 hospitalization and infection, repaglinide against infection, and insulin and sulfonylureas show to be risk factors for COVID-19 hospitalization and infection. Further research in T2DM-CKD is needed.

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“…On the other hand, there have been studies that found otherwise and showed no beneficial effects of DPP-IV blockade [57,58]. Recent evidence suggests that DPP-IV and its inhibitors play a role in the pathogenesis of severe COVID-19 [59,60]. Nevertheless, this area requires further research to elucidate its exact role in mediating severe manifestation of the disease, especially when clinical trials investigating DPP-IV inhibitors in the COVID-19 management provide conflicting results.…”

Section: Discussionmentioning

confidence: 99%

VEGFR and DPP-IV as Markers of Severe COVID-19 and Predictors of ICU Admission

Pius-Sadowska,

Kulig,

Niedźwiedź

et al. 2023

IJMS

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The pathophysiology of the severe course of COVID-19 is multifactorial and not entirely elucidated. However, it is well known that the hyperinflammatory response and cytokine storm are paramount events leading to further complications. In this paper, we investigated the vascular response in the pathophysiology of severe COVID-19 and aimed to identify novel biomarkers predictive of ICU admission. The study group consisted of 210 patients diagnosed with COVID-19 (age range: 18–93; mean ± SD: 57.78 ± 14.16), while the control group consisted of 80 healthy individuals. We assessed the plasma concentrations of various vascular factors using the Luminex technique. Then, we isolated RNA from blood mononuclear cells and performed a bioinformatics analysis investigating various processes related to vascular response, inflammation and angiogenesis. Our results confirmed that severe COVID-19 is associated with vWF/ADAMTS 13 imbalance. High plasma concentrations of VEGFR and low DPP-IV may be potential predictors of ICU admission. SARS-CoV-2 infection impairs angiogenesis, hinders the generation of nitric oxide, and thus impedes vasodilation. The hypercoagulable state develops mainly in the early stages of the disease, which may contribute to the well-established complications of COVID-19.

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Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Cited by 5 publications

References 64 publications

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity

Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis

VEGFR and DPP-IV as Markers of Severe COVID-19 and Predictors of ICU Admission

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