COVID-19 Evidence Alerts
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Current best evidence for clinical care (more info)

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Treatment Pal R, Banerjee M, Mukherjee S, et al. Dipeptidyl peptidase-4 inhibitor use and mortality in COVID-19 patients with diabetes mellitus: an updated systematic review and meta-analysis. Ther Adv Endocrinol Metab. 2021 Feb 20;12:2042018821996482. doi: 10.1177/2042018821996482. eCollection 2021.

Background: Few observational studies have shown a beneficial effect of dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with coronavirus disease 2019 (COVID-19), although results are not consistent. The present systematic review and meta-analysis was undertaken to provide a precise summary of the effect of DPP4i use (preadmission or in-hospital) and mortality in COVID-19 patients with diabetes mellitus (DM).

Methods: PubMed and Google Scholar databases were systematically searched using appropriate keywords to 4 January 2021, to identify observational studies reporting mortality in COVID-19 patients with DM using DPP4i versus those not using DPP4i. Preadmission and in-hospital use of DPP4i were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Subgroup analysis was performed for studies reporting preadmission and in-hospital use of DPP4i.

Results: We identified nine observational studies of high quality pooling data retrieved from 7008 COVID-19 patients with DM. The pooled analysis of unadjusted and adjusted data did not show any significant association between DPP4i use and mortality in COVID-19 patients with DM. However, on subgroup analysis, we found that in-hospital (and not preadmission) DPP4i use was associated with reduced mortality (unadjusted OR 0.37, 95% CI 0.23, 0.58, p < 0.0001, I2 = 0% and adjusted OR 0.27, 95% CI 0.13, 0.55, p = 0.0003, I2 = 12%).

Conclusions: In-hospital use of DPP4i is associated with a significant reduction in COVID-19 mortality. Hence, it would be prudent to initiate or continue DPP4i in COVID-19 patients with DM if not contraindicated.

Discipline / Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Endocrine rater

This is a good study that reviewed 9 observational studies and showed that DPP-IV inhibitors decrease the risk of COVID-19 mortality.

Hospital Doctor/Hospitalists rater

I can't dispel the concern that there might be a sample selection bias in each study. However, the results of the present meta-analysis are convincing enough to go ahead with conducting RCTs.

Internal Medicine rater

There was no association between DPP4-inhibitors and survival benefit. The authors concluded this from the af subgroup analysis of this observational study; I disagree with this. We need a RCT to conclude whether patients with Covid-19 benefit from treatment with DPP4-inhibitors or not.