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Home Treatment with GLP-1 Receptor Agonists and SGLT2 Inhibitors May Reduce ICU Admission and Death in People with Type 2 Diabetes During Early COVID-19
The overall for hospitalized patients with Type 2 diabetes and COVID-19 was 14.29%, with a significantly higher rate of 53.62% among those infected.
Patients with Type 2 diabetes treated with DPP-4 inhibitors had a markedly higher risk of in-hospital death, with an of 4.02 compared to those on GLP-1 receptor agonists.
Death rates were significantly lower for patients treated with GLP-1 receptor agonists and SGLT-2 inhibitors, at nearly a quarter of the overall mortality observed.
Longer hospital stays were associated with increased mortality, ranging from 22.3% for stays of three days or less to 77.4% for stays longer than 14 days.
SGLT-2 inhibitors and GLP-1 receptor agonists may provide protective effects beyond glucose control, potentially reducing inflammation and benefiting lung tissue.
Simplified
INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a relevant risk factor for severe forms of COVID-19 (SARS coronavrus 2 [SARS-CoV-2] disease 2019), and calls for caution because of the high prevalence of T2DM worldwide and the high mortality rates observed in patients with T2DM who are infected with SARS-CoV-2. People with T2DM often take dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1ras), sodium-glucose co-transporter-2 inhibitors (SGLT-2is), all of which have clear anti-inflammatory effects. The study aimed to compare (i) the severity and duration of hospital stay between patients with T2DM categorized by pre-hospitalization drug class utilization and (ii) the COVID-19-related death rates of those three groups.
METHODS: We designed an observational, retrospective, multi-center, population-based study and extracted the hospital admission data from the health care records of 1916 T2DM patients over 18 years old who were previously on GLP-1ra, SGLT-2i, or DPP-4i monotherapy and were hospitalized for COVID-19 (diagnosis based on ICD.9/10 codes) between January 2020 and December 2021 in 14 hospitals throughout Italy. We analyzed general data, pre-admission treatment schedules, date of admission or transfer to the intensive care unit (ICU) (i.e., the index date; taken as a marker of increased COVID-19 disease severity), and death (if it had occurred). Statistics analyzed the impact of drug classes on in-hospital mortality using propensity score logistic regressions for (i) those admitted to intensive care and (ii) those not admitted to intensive care, with a random match procedure used to generate a 1:1 comparison without diabetes cohort replacement for each drug therapy group by applying the nearest neighbor method. After propensity score matching, we checked the balance achieved across selected variables if a balance was ever achieved. We then used propensity score matching between the three drug classes to assemble a sample in which each patient receiving an SGLT-2i was matched to one on a GLP-1ra, and each patient on a DPP-4i was matched to one on a GLP-1ra, adjusting for covariates. We finally used GLP-1ras as references in the logistic regression.
RESULTS: The overall (MR) of the patients was 14.29%. The MR in patients with COVID was 53.62%, and it was as high as 42.42% in the case of associated T2DM, regardless of any glucose-lowering therapy. In those on DPP-4is, there was excess mortality; in those treated with GLP-1ras and SGLT-2is, the death rate was significantly lower, i.e., almost a quarter of the overall mortality observed in COVID-19 patients with T2DM. Indeed, the odds ratio (OR) in the logistic regression resulted in an extremely high risk of in-hospital death in individuals previously treated with DPP-4is [incidence rate (IR) 4.02, 95% confidence interval (CI) 2.2-5.7) and only a slight, nonsignificantly higher risk in those previously treated with SGLT-2is (IR 1.42, 95% CI 0.6-2.1) compared to those on GLP-1ras. Moreover, the longer the stay, the higher the death rate, which ranged from 22.3% for ≤ 3-day stays to 40.3% for 4- to 14-day stays (p < 0.01 vs. the former) and 77.4% for over-14-day stays (p < 0.001 vs. both the others).
DISCUSSION: Our data do not support a protective role of DPP-4is; indeed, this role has already been questioned due to previous observations. However, the data do show a strong protective effect of SGLT-2is and GLP-1ras. Beyond lowering circulating glucose levels, those two drug classes were found to exert marked anti-phlogistic effects: SGLT-2is increased adiponectin and reduced urate, leptin, and insulin concentrations, thus positively affecting overall low-grade inflammation, and GLP-1ras may also greatly help at the lung tissue level, meaning that their extra-glycemic effects extend well beyond those acknowledged in the cardiovascular and renal fields.
CONCLUSIONS: The aforedescribed observational clinical data relating to a population of Italian inpatients with T2DM suggest that GLP-1ras and SGLT-2is can be considered antidiabetic drugs of choice against COVID-19, and might even prove beneficial in the event of any upcoming pandemic that has life-threatening effects on the pulmonary and cardiovascular systems.
Key numbers
14.29%
Overall
Percentage of deaths among all hospitalized T2DM patients.
309 units of death per 1000 individuals
in DPP-4is Group
Death rate specifically for T2DM patients on DPP-4is.
77.4%
by ICU Stay Duration
for patients with ICU stays over 14 days.
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