Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis

Abstract

AimsWe conducted a systematic review and meta-analysis to assess various antidiabetic agents’ association with mortality in patients with type 2 diabetes (T2DM) who have coronavirus disease 2019 (COVID-19).MethodsWe performed comprehensive literature retrieval from the date of inception until February 2, 2021, in medical databases (PubMed, Web of Science, Embase, and Cochrane Library), regarding mortality outcomes in patients with T2DM who have COVID-19. Pooled OR and 95% CI data were used to assess relationships between antidiabetic agents and mortality.ResultsEighteen studies with 17,338 patients were included in the meta-analysis. Metformin (pooled OR, 0.69; P=0.001) and sulfonylurea (pooled OR, 0.80; P=0.016) were associated with lower mortality risk in patients with T2DM who had COVID-19. However, patients with T2DM who had COVID-19 and received insulin exhibited greater mortality (pooled OR, 2.20; P=0.002). Mortality did not significantly differ (pooled OR, 0.72; P=0.057) between DPP-4 inhibitor users and non-users.ConclusionsMetformin and sulfonylurea could be associated with reduced mortality risk in patients with T2DM who have COVID-19. Furthermore, insulin use could be associated with greater mortality, while DPP-4 inhibitor use could not be. The effects of antidiabetic agents in patients with T2DM who have COVID-19 require further exploration.Systematic Review RegistrationPROSPERO (identifier, CRD42021242898).

Commentary: Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis

“…In Kan and colleagues’ article ( 1 ) the authors did not perform meta-analysis to assess the association between use of SGLT2i and GLP1RA and risk of COVID-19 mortality since they included only one SGLT2i study ( 7 ) and two GLP1RA studies ( 9 , 10 ). On the contrary, we conducted meta-analysis respectively based on 6 SGLT2i studies ( 2 – 7 ) and 6 GLP1RA studies ( 2 , 3 , 6 , 8 – 10 ), and accordingly revealed the significant association of SGLT2i use with a 22% reduction in COVID-19 mortality risk, and of GLP1RA use with a 25% reduction in that risk.…”

“…On the contrary, we conducted meta-analysis respectively based on 6 SGLT2i studies ( 2 – 7 ) and 6 GLP1RA studies ( 2 , 3 , 6 , 8 – 10 ), and accordingly revealed the significant association of SGLT2i use with a 22% reduction in COVID-19 mortality risk, and of GLP1RA use with a 25% reduction in that risk. Moreover, Kan et al’s meta-analysis ( 1 ) did not include 8 recently-published DPP4i studies ( 2 – 4 , 8 , 11 – 14 ), which limited its statistical power. Accordingly, a statistically significant difference between DPP4i and Non-DPP4i was not observed in that meta-analysis ( 1 ).…”

“…Moreover, Kan et al’s meta-analysis ( 1 ) did not include 8 recently-published DPP4i studies ( 2 – 4 , 8 , 11 – 14 ), which limited its statistical power. Accordingly, a statistically significant difference between DPP4i and Non-DPP4i was not observed in that meta-analysis ( 1 ). In contrast, this updated meta-analysis included 16 DPP4i studies ( 2 – 4 , 7 – 14 , 16 – 20 ) including the 8 recent ones ( 2 – 4 , 8 , 11 – 14 ), and therefore with sufficient statistical power identified that DPP4i use versus Non-DPP4i use was significantly associated with a 17% reduction in COVID-19 mortality risk.…”

“…In a recent article ( 1 ), Kan and colleagues assessed the association between use of four kinds of hypoglycemic agents (i.e., metformin, sulfonylurea, dipeptidyl peptidase-4 inhibitors [DPP4i], and insulin) and risk of COVID-19 mortality in patients with type 2 diabetes mellitus (T2DM), by performing meta-analysis based on eligible studies. However, the authors did not address the association of two novel classes of hypoglycemic agents (i.e., sodium-glucose cotransporter-2 inhibitors [SGLT2i] and glucagon-like peptide-1 receptor agonists [GLP1RA]) with COVID-19 mortality, due to the limited number of included studies regarding SGLT2i and GLP1RA.…”

“…Therefore, we intended to include these recent studies regarding SGLT2i and GLP1RA to conduct an updated meta-analysis to address their association with COVID-19 mortality in T2DM patients. Moreover, several new cohort studies ( 2 – 4 , 8 , 11 – 14 ) targeting the relationship of DPP4i use with COVID-19 death risk have been published after Kan et al’s meta-analysis ( 1 ). Thus, in this updated meta-analysis we would also include these new DPP4i studies to reassess the association between use of DPP4i and risk of COVID-19 death in T2DM patients.…”