Association Between Glucagon-Like Peptide 1 Receptor Agonist and Sodium–Glucose Cotransporter 2 Inhibitor Use and COVID-19 Outcomes

Abstract

To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODSWe analyzed observational data from SARS-CoV-2-positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018-February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTSThe study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37-0.80] and 0.66 [0.50-0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONSAmong SARS-CoV-2-positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.

The role of GLP-1 receptor agonists during COVID-19 pandemia: a hypothetical molecular mechanism

“…Yet, there is still insufficient evidence to clarify the benefit of GLP-1RAs in patients with T2D and SARS-CoV2 infection, so far mainly limited to data obtained from retrospective analyses of few databases. In the US, the National COVID Cohort Collaborative (N3C) Consortium have performed the analysis of observational data from SARS-CoV-2-positive adults with a prescription for GLP1-RAs, sodium-glucose cotransporter 2 inhibitors (SGLT2i) inhibitors or dipeptidyl peptidase 4 inhibitors (DPP4i) within 24 months of positive SARS-CoV-2 PCR test [ 39 ]. Interestingly, the authors have very recently reported that premorbid GLP1-RAs and SGLT2i use, compared with DPP4i usage, was associated with lower odds of mortality and other adverse outcomes, such as emergency room visits and hospitalizations [ 39 ].…”

Use of Novel Antidiabetic Agents in Patients with Type 2 Diabetes and COVID-19: A Critical Review

“…The risks of hospital admission, ICU admission and mechanical ventilation were overall similar in DPP4i and GLP-1RAs users vs. SGLT2i users [ 47 ]. In addition, the recently published observational study from the National COVID Cohort Collaborative (N3C), including 12,446 SARS-CoV-2-positive adults, with 60-day mortality as primary outcome, showed that both GLP1-RAs and SGLT2i use were associated with lower 60-day mortality compared to DPP4i use [ 48 ].…”

“…However, the risks of hospital admission, ICU admission and mechanical ventilation were overall similar for all of three studied drug classes [ 47 ]. The previously cited observational study showed that both GLP1-RAs and SGLT2i usage were associated with lower 60-day mortality in comparison to DPP4i usage [ 48 ]. Further, a Spanish multicentre observational study enrolling very old patients with T2DM and COVID-19 showed no association between preadmission use of SGLT2i and in-hospital mortality [ 34 ].…”

“…In a previously cited multinational retrospective cohort study, using data from a COVID-19 Research Network, GLP-1RAs users were hallmarked by the significant reductions in mortality (47%) and in hospital admissions (40%), including a reduction in respiratory complications (46%) [ 35 ]. A previously mentioned observational study from the National COVID Cohort Collaborative (N3C) group demonstrated that both GLP1-RAs and SGLT2i use were associated with lower 60-day mortality compared to DPP4i use [ 48 ]. Additionally, a population-based study using data from nationwide registries revealed that GLP-1RAs users had similar 30-day mortality to SGLT2i users, and that users of both of these drug classes had lower 30-day mortality than DPP4i users [ 47 ], while the risks of hospital admission, ICU admission and mechanical ventilation were overall similar in GLP-1RAs and DPP4i users in comparison to SGLT2i users [ 47 ].…”

Narrative review on clinical considerations for patients with diabetes and COVID‐19: More questions than answers

“… 51 Overall, GLP‐1 RAs have been shown to exhibit anti‐inflammatory actions. 52 It should be noted that data from human studies on the effects of DPP4 inhibitors and GLP‐1 RAs on the incidence and treatment of COVID‐19 is limited to a few observational studies 45 , 53 , 54 , 55 but there are ongoing randomised clinical trials. 56 , 57 , 58…”