Dipeptidyl Peptidase-4 Inhibitors and COVID-19-Related Deaths among Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies

Patoulias, Dimitrios; Doumas, Michael

doi:10.3803/enm.2021.1048

Cited by 24 publications

(24 citation statements)

References 21 publications

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“…Moreover, beyond their glucose-lowering effects, these drugs have several pleiotropic protective properties, which include anti-inflammatory and immunomodulatory activities, antifibrotic and antithrombotic effects, and vascular endothelial protective properties which may be responsible for their potential favorable impact on clinical outcomes in diabetic people with COVID-19 [ 5 , 45 ]. There is also evidence from observational studies that DPP-4i decrease the risk for COVID-19-related death [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Improvement of glycemic control and reduction of major cardiovascular events in 18 cardiovascular outcome trials: an updated meta-regression

Maiorino

Longo

Scappaticcio

et al. 2021

Cardiovasc Diabetol

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Background Besides providing reassurance about cardiovascular (CV) safety of newer diabetes drugs, cardiovascular outcome trials (CVOTs) have also shown encouraging benefits on some CV endpoints. The contribution of the better glycemic control in the reduction of major cardiovascular events (MACE) remains an open question. The aim of this study is to evaluate the associations between the reduction of HbA1c and risk of MACE, MACE components, hospitalization for heart failure (HF) and all-cause death in CVOTs. Methods An electronic search up to July 2021 was conducted to determine eligible trials. Systematic review identified eighteen CVOTs reporting prespecified CV outcomes. Pooled summary estimates and 95% confidence intervals (CI) were calculated according to the random effects model using the Paule-Mandel method; restricted maximum likelihood estimators were used to estimate model parameters in the metaregression. Results The eighteen CVOTs evaluated 161,156 patients and included four trials with dipeptidyl-peptidase-4 inhibitors (DPP-4i), eight trials with glucagon-like peptide-1 receptor agonists (GLP-1RA) and six trials with sodium-glucose cotransporter-2 inhibitors (SGLT-2i). Random-effects model meta-analysis showed an association between treatment and risk of MACE (hazard ratio [HR] 0.90; 95% CI 0.86, 0.94, P < 0.001), with significant heterogeneity between studies (I2 = 45.2%, Q statistic P = 0.040). In meta-regression, there was an association between the reduction in HbA1c at the end of the trial and the HR reduction for MACE (beta = − 0.298, P = 0.007), with significant heterogeneity (I2 = 40%, Q statistic P = 0.04); this association was totally driven by the risk reduction of non-fatal stroke, which explained 100% of between-study variance (beta = − 0.531, R2 = 100%), without heterogeneity (I2 = 24%, Q statistic P = 0.206). There was no association between the reduction in HbA1c and the HR for heart failure or all-cause death. Conclusions The reduction of HbA1c in eighteen CVOTs was significantly associated with reduction of non-fatal stroke, explaining all (R2 = 100%) of the between-study variance. While the contribution of glucose lowering in some CV benefits of newer agents does not influence their indications for the patient with type 2 diabetes, it may hopefully facilitate their use.

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Section: Discussionmentioning

confidence: 99%

Improvement of glycemic control and reduction of major cardiovascular events in 18 cardiovascular outcome trials: an updated meta-regression

Maiorino

Longo

Scappaticcio

et al. 2021

Cardiovasc Diabetol

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“…DPP4 inhibitors in patients with DM2 have been used for a long time since 2006, with good tolerance and few adverse reactions reported [ 66 ]. The role of DPP-4 inhibition as an inflammation mitigator and potent antifibrotic agent is supported by several experimental studies [ 67 ].…”

Section: How Antidiabetic Treatment Influences Sars-cov-2 Infectionmentioning

confidence: 99%

Type 2 Diabetes Mellitus and COVID-19: A Narrative Review

et al. 2022

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Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder. The incidence and prevalence of patients with T2DM are increasing worldwide, even reaching epidemic values in most high- and middle-income countries. T2DM could be a risk factor of developing complications in other diseases. Indeed, some studies suggest a bidirectional interaction between T2DM and COVID-19. A growing body of evidence shows that COVID-19 prognosis in individuals with T2DM is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with T2DM after SARS-CoV-2 infection. The most common treatments for T2DM may influence SARS-CoV-2 and their implication in infection is briefly discussed in this review. A better understanding of the link between TD2M and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.

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“…Although decreased mortality and respiratory complications were also found among similar studies, Patoulias et al and Yang et al showed no significant results possibly due to small sample size [ [28] , [29] , [30] , [31] , [32] , [33] ]. Study that were conducted by Patoulias et al also showed a difference between inpatient and outpatient settings in which inpatient setting is associated with significant effect of reduced mortality (RR, 0.50; 95% CI, 0.34 to 0.71; I 2 = 0%; P = 0.0001) while the latter showed no significant effect (RR, 1.14; 95% CI, 0.78 to 1.66; I 2 = 81%; P = 0.50) [ 28 ]. A baseline use of DPP-IV inhibitors is also associated with a decreased hazard of endpoints in COVID-19 infection, as demonstrated by Luk et al [ 32 ].…”

Section: Discussionmentioning

confidence: 83%

Dipeptidyl peptidase-4 (DPP-IV) inhibitor was associated with mortality reduction in COVID-19 — A systematic review and meta-analysis

Zein

Raffaello

2022

Primary Care Diabetes

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Introduction This systematic review and meta-analysis aimed to synthesize the latest evidence on the effect of dipeptidyl peptidase-4 (DPP-IV) inhibitor in patients with COVID-19. Methods We performed a systematic literature search from the PubMed, Scopus, Embase, and Clinicaltrials.gov up until 15 July 2021. Studies that met the following criteria were included: prospective or retrospective observational studies or case series or randomized controlled trials (RCTs) reporting DPP-IV inhibitor use in patients with COVID-19 and mortality. The intervention group was patients receiving DPP-IV inhibitor. The control group was patients that did not receive DPP-IV inhibitor. The outcome was mortality reported as odds ratio (OR). Results There were 11 studies consisting of 5,950 patients in this meta-analysis. DPP-IV inhibitor use was associated with reduced mortality (OR 0.75 [0.56, 0.99], p = 0.043, I 2 : 42.9, p = 0.064) compared to those that did not receive DPP-IV inhibitor. Sensitivity analysis using the fixed-effect model (OR 0.75 [0.63, 0.88], p < 0.001, I 2 : 42.9, p = 0.064) also showed mortality benefit. The association between DPP-IV inhibitor and mortality was not significantly affected by age (p = 0.540), sex (p = 0.054), hypertension (p = 0.320), location (continent; p = 0.532), and retrospective/prospective nature of the study (p = 0.840). However, the association was affected by metformin (OR 1.03 [95% CI 1.01, 1.06], p = 0.010) and ACEI/ARB use (OR 1.06 [95% CI 1.02, 1.10], p = 0.004). Conclusion This meta-analysis showed that DPP-IV inhibitor was associated with reduced mortality in patients with COVID-19.

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Dipeptidyl Peptidase-4 Inhibitors and COVID-19-Related Deaths among Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies

Cited by 24 publications

References 21 publications

Improvement of glycemic control and reduction of major cardiovascular events in 18 cardiovascular outcome trials: an updated meta-regression

Improvement of glycemic control and reduction of major cardiovascular events in 18 cardiovascular outcome trials: an updated meta-regression

Type 2 Diabetes Mellitus and COVID-19: A Narrative Review

Dipeptidyl peptidase-4 (DPP-IV) inhibitor was associated with mortality reduction in COVID-19 — A systematic review and meta-analysis

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