The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis

Lukito, Antonia Anna; Pranata, Raymond; Henrina, Joshua; Lim, Michael Anthonius; Lawrensia, Sherly; Suastika, Ketut

doi:10.1016/j.dsx.2020.11.006

Cited by 77 publications

(77 citation statements)

References 26 publications

(34 reference statements)

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“…The result of our meta-analysis showed that metformin was associated with a statistically significant reduced mortality for diabetic patients with COVID-19, both before and after adjusting for other factors. This was consistent with several previous small-scale meta-analyses(39, 40). Home use of metformin was more effective compared to in-hospital use, which was shown in previous analyses(41).…”

Section: Discussionsupporting

confidence: 93%

The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

Han

Sun

et al. 2021

Preprint

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BackgroundDuring the current Coronavirus Disease 2019 (COVID-19) pandemic, diabetic patients face disproportionately more. Anti-inflammatory effects of hypoglycemic agents have been reported, and their beneficial or harmful effects in patients with diabetes and COVID-19 remain controversial.PurposeThis study was performed to clarify this association.Data SourcesRelevant literature was searched on China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, Chinese periodical service platform VIP Database, Sinomed (China Biology Medicine, CBM), MedRxiv, PubMed, ScienceDirect, Web of Science, Ovid Databases (LWW), Springer Link, Wiley Online Library, Oxford Academic, Nature Press Group, Cochrane Library and BMJ Evidence-Based Medicine up to November 14, 2020.Study SelectionOnly observational studies of hypoglycemic agents vs. drugs or therapy without hypoglycemic agents in adult diabetic patients with COVID-19 were included.Data ExtractionData of death and poor composite outcomes were extracted.Data SynthesisThe pooled effects were calculated using the fixed-effects or random-effects models based on heterogeneity assessment.LimitationMost studies were retrospective cohort studies with relative weak capability to verify causality.ConclusionHome use of metformin might be beneficial in decreasing mortality in diabetic patients infected with SARS-CoV-2. There is insufficient evidence to conclude that metformin and other hypoglycemic agents are associated with poor composite outcomes. More prospective studies, especially RCTs are needed.Registration-PROSPEROCRD42020221951.

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Section: Discussionsupporting

confidence: 93%

The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

Han

Sun

et al. 2021

Preprint

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“…Metformin and ACE/ARB have been shown to reduce mortality in patients with COVID-19 [ 17 , 18 ], these drugs are frequently prescribed in patients with diabetes. Possible explanation is that, the benefit of DPP-4 inhibitor in terms of mortality is reduced by the presence of the two drugs.…”

Section: Discussionmentioning

confidence: 99%

“…A number of non-communicable diseases such as hypertension, cardiovascular and cerebrovascular disease, chronic kidney disease, and chronic lung disease are also considered comorbidities for COVID-19, as well as increasing age, body mass index, and frailty conditions [ [25] , [26] , [27] , [28] , [29] , [30] , [31] ]. Recent evidences suggested that the use metformin, another anti-diabetic drug, and renin-angiotensin system (RAS) inhibitor were associated with lower severity and mortality in COVID-19 patients [ 17 , 32 ]. While these medications hamper hyperinflammation by affecting the ACE2 receptor, gliptin works by inhibiting DPP-4 [ [4] , [5] , [6] , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19) – A systematic review, meta-analysis, and meta-regression

Rakhmat

Kusmala

Handayani

et al. 2021

Diabetes & Metabolic Syndrome: Clinical Research & Revi

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Background and aims This study aims to synthesize evidence on dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in COVID-19 patients and factors affecting it. Methods We performed a systematic literature search from PubMed, Scopus, and Embase databases from inception of databases up until 7 March 2021. Studies that met all of the following criteria were included: 1) observational studies or randomized controlled trials that report COVID-19 patients, 2) reporting DPP-4 inhibitor use, 3) mortality, and 4) mortality based on DPP-4 inhibitor use. The exposure was DPP-4 inhibitor, defined as DPP-4 inhibitor use that started prior to COVID-19 hospitalization. The control group was patients with no exposure to DPP-4 inhibitor. The outcome was mortality. The pooled effect estimate was reported as risk ratio (RR). Results There were 4,477 patients from 9 studies in this systematic review and meta-analysis. 31% of (15%, 46%) the patients use DPP-4 inhibitor. Mortality occurs in 23% (15%, 31%) of the patients. DPP-4 inhibitor was associated with lower mortality in patients with COVID-19 (RR 0.76 [0.60, 0.97], p = 0.030, I2: 44.5%, p = 0.072). Meta-regression analysis showed that the association between DPP-4 inhibitor and mortality was significantly affected by metformin (RR 1.02 [1.00, 1.04], p = 0.048) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) use (RR 1.04 [1.01, 1.07], p = 0.006), but not age (p = 0.759), sex (reference: male, p = 0.148), and hypertension (p = 0.218). Conclusion DPP-4 inhibitor use was associated with lower mortality in COVID-19 patients, and the association was weaker in patients who were also taking metformin and/or ACE inhibitors.

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“…Meta-regression analysis in this study was only aimed to ruling in any association, not ruling them out. Certain medications such as angiotensin-receptor blocker and metformin was also shown to be associated with reduced severity [ 24 , 25 ]; although publication bias is very likely.…”

Section: Discussionmentioning

confidence: 99%

Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis

Pranata

Huang

Lawrensia³

et al. 2021

Pharmacol. Rep

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Background The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19. Methods We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants. Results There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3.03], p = 0.014; I 2 90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), non-steroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5.05], p = 0.46; I 2 99.7%). Conclusion This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility. PROSPERO ID: CRD42020224286.

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The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis

Cited by 77 publications

References 26 publications

The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19) – A systematic review, meta-analysis, and meta-regression

Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis

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