Dipeptidyl Peptidase-4 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, and Sodium-Glucose Cotransporter-2 Inhibitors and COVID-19 Outcomes

• Published in: Clinical therapeutics Vol. 45; no. 4; pp. e115 - e126
• Main Authors: Foresta, Andreana, Ojeda-Fernandez, Luisa, Macaluso, Giulia, Roncaglioni, Maria Carla, Tettamanti, Mauro, Fortino, Ida, Leoni, Olivia, Genovese, Stefano, Baviera, Marta
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2023; Elsevier Limited
• Subjects: Agonists; Clinical outcomes; Clinical trials; Cohort analysis; Coronaviruses; COVID-19; COVID-19 - complications; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; dipeptidyl peptidase-4 inhibitors; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - therapeutic use; GLP-1 receptor agonists; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; glucagon-like peptide-1 receptor agonists; Glucose; Hospitals; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Internal Medicine; Medical prognosis; Mortality; Observational studies; Original Research; outcomes; Pandemics; Peptides; Population; Prescription drugs; Sensitivity analysis; Severe acute respiratory syndrome coronavirus 2; Sodium - therapeutic use; Sodium-glucose cotransporter; sodium-glucose cotransporter-2 inhibitors; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Italy; COVID-19; dipeptidyl peptidase-4 inhibitors; sodium-glucose cotransporter-2 inhibitors; outcomes; glucagon-like peptide-1 receptor agonists
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2023.02.007

•DPP-4i, GLP-1 RA and SGLT-2i may have a positive impact on the dysregulated process of cytokine storm associated with COVID-19•We compared the effects of the association between DPP-4i, GLP-1 RA or SGLT-2i users and non-users on mortality and severity of COVID-19 patients with diabetes•We found a significant risk reduction for total mortality in DPP4i users compared to non-users•A positive trend was seen in hospital admission and in-hospital mortality for GLP1-RA and SGLT2i, respectively.•Waiting for the results of RCTs, according to our findings DPP-4i, GLP1-RA and SGLT-2i should not be discontinued in patients with diabetes and COVID-19. Purpose: It has been reported that dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have a role in modulation of inflammation associated with coronavirus disease 2019 (COVID-19). This study assessed the effect of these drug classes on COVID-19–related outcomes. Methods: Using a COVID-19 linkable administrative database, we selected patients aged ≥40 years with at least 2 prescriptions of DPP-4i, GLP-1 RA, or SGLT-2i or any other antihyperglycemic drug and a diagnosis of COVID-19 from February 15, 2020, to March 15, 2021. Adjusted odds ratios (ORs) with 95% CIs were used to calculate the association between treatments and all-cause and in-hospital mortality and COVID-19–related hospitalization. A sensitivity analysis was performed by using inverse probability treatment weighting. Findings: Overall, 32,853 subjects were included in the analysis. Multivariable models showed a reduction of the risk for COVID-19 outcomes for users of DPP-4i, GLP-1 RA, and SGLT-2i compared with nonusers, although statistical significance was reached only in DPP-4i users for total mortality (OR, 0.89; 95% CI, 0.82–0.97). The sensitivity analysis confirmed the main results reaching a significant reduction for hospital admission in GLP-1 RA users and in-hospital mortality in SGLT-2i users compared with nonusers. Implications: This study found a beneficial effect in the risk reduction of COVID-19 total mortality in DPP-4i users compared with nonusers. A positive trend was also observed in users of GLP-1 RA and SGLT-2i compared with nonusers. Randomized clinical trials are needed to confirm the effect of these drug classes as potential therapy for the treatment of COVID-19. [Display omitted]