Table 1.
Summary of studies evaluating the use of novel antidiabetic agents in patients with T2DM and COVID-19
| Authors | Study design | Primary outcome | N of patients | Main results |
|---|---|---|---|---|
| DPP4i | ||||
| Solerte [32] | Multicentre, case–control, retrospective, observational study; adding sitagliptin to standard of care | Discharge from hospital, improvement of clinical outcomes and mortality | 338 |
Positive Reduced mortality, improvement in clinical outcomes, greater number of hospital discharges with sitagliptin |
| Mirani [33] | Single-centre, case series; evaluating the use of DPP4i | Mortality | 90 |
Positive Lower risk of mortality with DPP4i |
| Ramos-Rincón [34] | Nationwide, multicentre observational study; evaluating use of several antidiabetic drugs, including DPP4i, GLP-1RAs and SGLT2i | Mortality | 790 |
Positive DPP4i were independent protectors for mortality; metformin, insulin, GLP-1RAs and SGLT2i had a neutral effect on mortality |
| Nyland [35] | Multinational retrospective cohort study; evaluating use of pioglitazone, GLP-1RAs and DPP4i in comparison to no use of such therapies | Mortality | 7769 |
Positive Significant reductions in mortality among users of pioglitazone, GLP-1RAs and DPP4i in comparison to non-users of pioglitazone, GLP-1RAs or DPP4i |
| Sainsbury [36] | Propensity score-matched cohort study, evaluating SGLT2i use in comparison to DPP4i | Confirmed or clinically suspected COVID-19 | 24,865 |
Neutral Similar risk of confirmed or clinically suspected COVID-19 |
| Izzi-Engbeaya [37] | Multicentre retrospective cohort study; evaluating use of insulin, GLP-1RAs, metformin, sulfonylurea, SGLT2i and DPP4i | Death and/or ICU admission within 30 days of COVID-19 diagnosis | 278 |
Neutral No association between insulin, GLP-1RAs, metformin, sulfonylurea, SGLT2i and DPP4i use and the risk of death and/or ICU admission within 30 days of COVID-19 |
| Silverii [38] | Retrospective observational study; evaluating use of metformin, pioglitazone, insulin, sulfonylurea/ glinides, DPP4i, SGLT2i and GLP-1RAs | COVID-19 prevalence and case fatality | 159 |
Neutral No association with COVID-19 prevalence; metformin use associated with a lower case fatality |
| Orioli [39] | Retrospective single-centre cohort study; evaluating use of different antidiabetic medications | In-hospital mortality | 73 |
Neutral Non-survivors were less often treated with metformin prior to admission in comparison to survivors |
| Wargny [40] | Update on the results of nationwide CORONADO study; evaluating use of metformin, sulfonylurea/ glinides, DPP4i, GLP-1RAs and insulin | Hospital discharge and death within 28 days | 2796 |
Neutral Routine metformin therapy was one of the predictors of discharge on day 28 and negatively associated with death within 28 days; routine insulin therapy was associated with greater risk of death within 28 days |
| Noh [41] | Nationwide cohort study; evaluating use of DPP4i | All-cause mortality | 586 |
Negative DPP4i had no effect on all-cause mortality |
| Fadini [42] | Case–control study; evaluating use of DPP4i | Risk of hospitalisation | 85 |
Negative DPP4i had no effect on the risk of hospitalisation |
| Strollo [43] | Review of medical charts; evaluating geographical differences in DPP4i use | Prevalence of diabetes among COVID-19 deaths | 3351 |
Negative Geographical differences did not correlate with diabetes prevalence among COVID-19 deaths |
| Roussel [44] | Secondary analysis of the nationwide CORONADO study; evaluating DPP4i use | Tracheal intubation for mechanical ventilation and death within 7 days of admission | 2449 |
Negative DPP4i had no effect on tracheal intubation for mechanical ventilation and death within 7 days of admission occurred at similar rates |
| Zhou [45] | Multicentre retrospective analysis; evaluating DPP4i use | 28-day all-cause mortality | 1257 |
Negative DPP4i had no effect on all-cause mortality |
| Dalan [46] | Retrospective, observational cohort study; evaluating use of DPP4i, SGLT2i and sulfonylureas | Hypoxia, ICU admission, mechanical ventilation or death | 76 |
Negative DPP4i associated with higher risk of ICU admission and mechanical ventilation, SGLT2i associated with lower risk of mechanical ventilation |
| Israelsen [47] | Population-based cohort study; evaluating use of SGLT2i in comparison to DPP4i and GLP-1RAs | Death within 30 days after a positive SARS CoV-2 test | 996 |
Negative Higher 30-day mortality compared to SGLT2i |
| Kahkoska [48] | National observational study, evaluating use of GLP-1RAs, SGLT2i and DPP4i | 60-day mortality | 12,446 |
Negative GLP1-RAs and SGLT2i use both associated with lower 60-day mortality in comparison to DPP4i use |
| SGLT2i | ||||
| Dalan [46] | Retrospective, observational cohort study; evaluating use of DPP4i, SGLT2i and sulfonylureas | Hypoxia, ICU admission, mechanical ventilation or death | 76 |
Positive SGLT2i associated with lower risk of mechanical ventilation; DPP4i associated with higher risk of ICU admission and mechanical ventilation |
| Israelsen [47] | Population-based cohort study; evaluating use of SGLT2i in comparison to DPP4i and GLP-1RAs | Death within 30 days after a positive SARS CoV-2 test | 996 |
Positive vs. DPP4i Neutral vs. GLP-1RAs Similar 30-day mortality compared to GLP-1RAs users and lower 30-day mortality compared to DPP4i |
| Kahkoska [48] | National observational study, evaluating use of GLP-1RAs, SGLT2i and DPP4i | 60-day mortality | 12,446 |
Positive GLP1-RAs and SGLT2i use both associated with lower 60-day mortality in comparison to DPP4i use |
| Ramos-Rincón [34] | Nationwide, multicentre observational study; evaluating use of several antidiabetic drugs, including DPP4i, GLP-1RAs and SGLT2i | Mortality | 790 |
Neutral DPP4i were independent protectors for mortality; metformin, insulin, GLP-1RAs and SGLT2i had a neutral effect on mortality |
| Sainsbury [36] | Propensity score-matched cohort study, evaluating SGLT2i use in comparison to DPP4i | Confirmed or clinically suspected COVID-19 | 24,865 |
Neutral Similar risk of confirmed or clinically suspected COVID-19 |
| Izzi-Engbeaya [37] | Multicentre retrospective cohort study; evaluating use of insulin, GLP-1RAs, metformin, sulfonylurea, SGLT2i and DPP4i | Death and/or ICU admission within 30 days of COVID-19 diagnosis | 278 |
Neutral No association between insulin, GLP-1RAs, metformin, sulfonylurea, SGLT2i and DPP4i use and the risk of death and/or ICU admission within 30 days of COVID-19 |
| Silverii [38] | Retrospective observational study; evaluating use of metformin, pioglitazone, insulin, sulfonylurea/glinides, DPP4i, SGLT2i and GLP-1RAs | COVID-19 prevalence and case fatality | 159 |
Neutral No association with COVID-19 prevalence; metformin use associated with a lower case fatality |
| Orioli [39] | Retrospective single-centre cohort study; evaluating use of different antidiabetic medications | In-hospital mortality | 73 |
Neutral Non-survivors were less often treated with metformin prior to admission in comparison to survivors |
| Kosiborod [57] | Randomised, double-blind, placebo-controlled trial; evaluating use of dapagliflozin in comparison to placebo among high-risk but not critically ill patients with COVID-19 | The outcome of prevention (time to new or worsened organ dysfunction or death) and the hierarchial composite outcome of recovery (change in clinical status by day 30) | 1250 |
Negative No significant impact on prevention of organ dysfunction, reduction in all-cause mortality and improvement in the clinical status (ranging from early recovery to death) at 30 days |
| GLP1-RAs | ||||
| Nyland [35] | Multinational retrospective cohort study; evaluating use of pioglitazone, GLP-1RAs and DPP4i in comparison to no use of such therapies | Mortality | 7769 |
Positive Significant reductions in mortality among users of pioglitazone, GLP-1RAs and DPP4i in comparison to non-users of pioglitazone, GLP-1RAs or DPP4i |
| Kahkoska [48] | National observational study, evaluating use of GLP-1RAs, SGLT2i and DPP4i | 60-day mortality | 12,446 |
Positive GLP1-RAs and SGLT2i use both associated with lower 60-day mortality in comparison to DPP4i use |
| Israelsen [47] | Population-based cohort study; evaluating use of SGLT2i in comparison to DPP4i and GLP-1RAs | Death within 30 days after a positive SARS CoV-2 test | 996 |
Positive vs. DPP4i Neutral vs. SGLT2i GLP-1RAs had similar 30-day mortality compared to SGLT2i users and lower 30-day mortality compared to DPP4i |
| Ramos-Rincón [34] | Nationwide, multicentre observational study; evaluating use of several antidiabetic drugs, including DPP4i, GLP-1RAs and SGLT2i | Mortality | 790 |
Neutral DPP4i were independent protectors for mortality; metformin, insulin, GLP-1RAs and SGLT2i had a neutral effect on mortality |
| Izzi-Engbeaya [37] | Multicentre retrospective cohort study; evaluating use of insulin, GLP-1RAs, metformin, sulfonylurea, SGLT2i and DPP4i | Death and/or ICU admission within 30 days of COVID-19 diagnosis | 278 |
Neutral No association between insulin, GLP-1RAs, metformin, sulfonylurea, SGLT2i and DPP4i use and the risk of death and/or ICU admission within 30 days of COVID-19 |
| Silverii [38] | Retrospective observational study; evaluating use of metformin, pioglitazone, insulin, sulfonylurea/ glinides, DPP4i, SGLT2i and GLP-1RAs | COVID-19 prevalence and case fatality | 159 |
Neutral No association with COVID-19 prevalence; metformin use associated with a lower case fatality |
COVID-19 coronavirus disease 2019, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, DPP4i dipeptidyl peptidase 4 inhibitors, GLP-1RAs glucagon-like peptide 1 receptor agonists, SGLT2i sodium-glucose co-transporter 2 inhibitors, CORONADO coronavirus SARS-CoV-2 and diabetes outcomes, ICU intensive care unit