Association of Glucose-Lowering Drugs With Outcomes in Patients With Diabetes Before Hospitalization for COVID-19

Abstract

ImportancePatients with COVID-19 have a high prevalence of diabetes, and diabetes and blood glucose control are determinants of intensive care unit admission and mortality.ObjectiveTo evaluate the association between COVID-19–related adverse outcomes and 8 antihyperglycemic drugs in patients with diabetes who were subsequently diagnosed and hospitalized with COVID-19.Data SourcesData were retrieved and collected in PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov from database inception to September 5, 2022.Study SelectionFor this systematic review and network meta-analysis, randomized clinical trials and observational studies conducted among patients with diabetes while receiving glucose-lowering therapies for at least 14 days before the confirmation of COVID-19 infection were included after blinded review by 2 independent reviewers and consultations of disagreement by a third independent reviewer. Of 1802 studies initially identified, 31 observational studies met the criteria for further analysis.Data Extraction and SynthesisThis study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Bayesian network meta-analyses were performed with random effects.Main Outcomes and MeasuresA composite adverse outcome, including the need for intensive care unit admission, invasive and noninvasive mechanical ventilation, or in-hospital death.ResultsThirty-one distinct observational studies (3 689 010 patients with diabetes hospitalized for COVID-19) were included. The sodium-glucose cotransporter-2 inhibitors (SGLT-2is) were associated with relatively lower risks of adverse outcomes compared with insulin (log of odds ratio [logOR], 0.91; 95% credible interval [CrI], 0.57-1.26), dipeptidyl peptidase-4 inhibitors (logOR, 0.61; 95% CrI, 0.28-0.93), secretagogues (logOR, 0.37; 95% CrI, 0.02-0.72), and glucosidase inhibitors (logOR, 0.50; 95% CrI, 0.00-1.01). Based on the surface under the cumulative ranking curves value, SGLT-2is were associated with the lowest probability for adverse outcomes (6%), followed by glucagon-like peptide-1 receptor agonists (25%) and metformin (28%). A sensitivity analysis revealed that the study was reliable.Conclusions and RelevanceThese findings suggest that the use of an SGLT-2i before COVID-19 infection is associated with lower COVID-19–related adverse outcomes. In addition to SGLT-2is, glucagon-like peptide-1 receptor agonists and metformin were also associated with relatively low risk of adverse outcomes.

Association Between Prehospital Blood Glucose Levels and Outcomes in Patients With COVID-19 Infection: A Retrospective Cohort Study

“…Several studies have been interested in this question and a meta-analysis has shown that in diabetic patients hospitalized with COVID, serum glucose transport protein-2 inhibitors taken before the hospitalization are associated with a lower risk of a bad outcome compared to insulin, dipeptidyl peptidase-4 inhibitors or sulfonylurea. In addition, taking glucagon-like peptide-1 or metformin also seems to be associated with a better outcome [32].…”

“…In addition, reliable information regarding oral hypoglycaemic medication was lacking. As it is known that such drugs are associated with lower risk of adverse effect than insulin [32], residual confounding cannot be excluded. Another risk of bias is linked to the important proportion of missing blood glucose values, which led to the exclusion of many patients.…”

COVID-19 and metabolic syndrome

“…Benefits and risks of common medications used in metabolic syndrome management in the setting of COVID-19 are an area of intense research and discussion and have been reviewed in detail elsewhere [68] , [69] , [70] , [71*] , [72] , [73] . Data from meta-analyses [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] , observational studies [25] and randomized controlled trials [84] , [85*] , [86] , [87] , [88*] , [89] have emerged while several studies are on-going. These are summarized in Table 2 .…”

Dissecting the Interrelationship between COVID‐19 and Diabetes Mellitus

“…[ 94a ] A meta‐analysis of 31 observational studies including more than 3.6 million COVID‐19 patients with pre‐existing T2DM, based on the surface under the cumulative ranking curves value shows that SGLT2i users had the lowest probability/possibility for adverse consequences followed by GLP1‐RA and metformin when compared to other anti‐hyperglycemic agent users. [ 97 ] More observational studies and randomized controlled trials need to be performed to shed more light on the use of SGLTi as a therapeutic drug against COVID‐19.…”