Reduced COVID-19 Mortality With Sitagliptin Treatment? Weighing the Dissemination of Potentially Lifesaving Findings Against the Assurance of High Scientific Standards
Michael A. Nauck, Juris J. Meier
Abstract
In this issue of Diabetes Care , two reports from northern Italy provide preliminary evidence that treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with type 2 diabetes hospitalized for coronavirus disease 2019 (COVID-19) reduce mortality. Solerte et al. (1) report on a retrospective case-control study describing a more than 50% reduction in mortality in 338 patients with type 2 diabetes hospitalized with pneumonia and impaired gas exchange during the initial wave of COVID-19 if they received sitagliptin treatment on top of insulin-based regimens as compared with insulin treatment alone. Mirani et al. (2) analyzed baseline conditions and outcomes in 385 patients hospitalized for COVID-19, 90 of whom had type 2 diabetes. In addition to predictors of mortality already described in previous studies (hypertension, coronary artery disease, chronic kidney disease, etc.), they found preexisting insulin treatment to be associated with worse outcomes (threefold higher mortality). Conversely, treatment with DPP-4 inhibitors was found to be associated with substantially and significantly lower mortality (hazard ratio 0.13 [95% CI 0.02–0.92] after adjustment for age and sex). It is obvious that such a marked therapeutic effect will receive widespread attention given the paucity of therapeutic approaches associated with convincing success. Certainly, such a prominent reduction in mortality has not been described with antiviral, glucocorticoid, or any other treatments. Therefore, the question arises, are the conclusions drawn from the present reports sufficiently robust to justify immediate changes in the treatment of patients with severe COVID-19 infections? Therefore, it is crucial to carefully consider the limitations and shortcomings of the reports by Solerte et al. and by Mirani et al. In the study of Solerte et al. (1), there was no random assignment to the treatment with sitagliptin, nor was there a placebo control or any attempt at blinded treatment. In fact, the use of …