Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study
Article Figures & Tables
Figures
- Figure 1
Mortality in patients with type 2 diabetes and COVID-19 treated with sitagliptin or receiving standard of care. A: Time to clinical end point (death/hospital discharge) in sitagliptin-treated patients and in the standard-of-care group. B: Bar graph representing mean blood glucose levels measured during the hospitalization in the two groups. Data are represented as mean ± SEM. No, number of patients.
- Figure 2
Subgroup analysis in patients (pts) with type 2 diabetes and COVID-19 treated with sitagliptin or receiving standard of care. Forest plots of subgroup analyses exploring the effect of treatment with sitaliptin/standard of care in patients with type 2 diabetes and COVID-19. Subgroups include age (≥70 or <70 years), sex (males or females), baseline HbA1c (>7.5% or ≤7.5%), and baseline BMI (>29 kg/m2 or ≤29 kg/m2).
Tables
- Table 1
Baseline demographic and clinical characteristics of patients
Characteristic Standard of care Sitagliptin P value Age (years) 69 ± 1.0 69 ± 0.9 0.83 Patients ≥70 years of age, n (%) 90 (53) 92 (54) 0.91 Male sex, n (%) 115 (68) 123 (73) 0.40 Duration of diabetes (years) 8.7 ± 1.2 9.2 ± 0.8 0.73 Coexisting conditions, n (%) Cardiovascular disease 53 (38) 65 (40) 0.63 Chronic kidney disease 34 (28) 34 (21) 0.26 Hypertension 80 (67) 118 (74) 0.23 Cancer 17 (14) 27 (17) 0.62 Glucose-lowering medications, n (%) Metformin 63 (39) 79 (44) 0.16 Insulin 48 (30) 39 (22) 0.15 Other oral antidiabetic agents 50 (31) 61 (34) 0.25 Antihypertensive drugs, n (%) ACE inhibitors 29 (50) 38 (38) 0.13 β-Blockers 34 (56) 32 (33) 0.007 Diuretics 30 (52) 36 (38) 0.13 Antiplatelet drugs, n (%) 29 (49) 39 (40) 0.32 Anticoagulant drugs, n (%) 52 (77) 74 (68) 0.17 Respiratory rate (breaths/min) 25.8 ± 0.7 23.7 ± 0.6 0.04 Clinical score (0–7) 4.4 ± 0.1 4.4 ± 0.08 0.88 BMI (kg/m2) 30 ± 0.6 29 ± 0.4 0.18 HbA1c (%) 7.5 ± 0.1 7.5 ± 0.1 0.66 HbA1c (mmol/mol) 58.6 ± 1.2 58.6 ± 1.3 0.98 Glycemia (mg/dL) 188 ± 6.8 180 ± 6.7 0.38 Serum creatinine (mg/dL) 1.4 ± 0.08 1.2 ± 0.08 0.10 Lymphocyte count (× 10−9/L) 0.9 ± 0.06 1.1 ± 0.17 0.13 CRP (mg/L) 19 ± 2.3 14 ± 0.7 0.01 D-dimer (μg/mL) 6,377 ± 1,928 5,835 ± 1,391 0.82 Interleukin-6 (ng/L) 95 ± 9.7 89 ± 10.7 0.71 LDH (units/L) 423 ± 43 387 ± 16 0.43 Ferritin (μg/mL) 601 ± 48 688 ± 97 0.43 AST (units/L) 42 ± 3.0 43 ± 2.6 0.79 ALT (units/L) 38 ± 2.4 40 ± 2.9 0.74 Procalcitonin (ng/mL) 12.7 ± 4.4 8.3 ± 3.3 0.42 Oxygen saturation (%) 92 ± 0.7 92 ± 0.5 0.31 Data are mean ± SEM unless otherwise indicated. Other oral antidiabetic agents are metformin, sulfonylureas, GLP-1-receptor agonists, DPP-4 inhibitors, sodium–glucose cotransporter 1 inhibitors, glinides, and thiazolidinediones.
↵LDH, lactate dehydrogenase.
- Table 2
Clinical outcomes in patients evaluated at follow-up (30 days)
Characteristic Standard of care Sitagliptin P value Mortality, n (%) 63 (37) 31 (18) 0.0001 Clinical score reduction, n (%) ≥2 points 50 (34) 72 (52) 0.0005 <2 points 67 (46) 36 (26) 0.0005 Overall improvement of clinical score, n (%) 55 (38) 83 (60) 0.0001 Hospital discharge at day 30, n 89 120 0.0008 EIR (IU/day) 31 ± 2.8 30 ± 3.8 0.83 Glycemia (mg/dL) 170 ± 9 139 ± 4 0.002*** Serum creatinine (mg/dL) 1.3 ± 0.1 1.0 ± 0.07 0.008* Lymphocyte count (× 10−9/L) 1.1 ± 0.07 1.6 ± 0.2 0.03^ CRP (mg/L) 7.1 ± 0.9 3.7 ± 0.5 0.001***^^^ D-dimer (μg/mL) 3,507 ± 1,082 2,693 ± 561 0.50* Interleukin-6 (ng/L) 81 ± 11 72 ± 10 0.55 LDH (units/L) 302 ± 21 370 ± 18 0.01^ Ferritin (μg/mL) 440 ± 43 411 ± 49 0.66*^ AST (units/L) 42 ± 4.6 28 ± 1.6 0.005*** ALT (units/L) 48 ± 5.5 43 ± 3.4 0.41 Procalcitonin (ng/mL) 8.9 ± 2.9 1.4 ± 0.5 0.01* Oxygen saturation (%) 92 ± 1.0 96 ± 0.7 0.004*** Data are mean ± SEM unless otherwise indicated.
EIR, exogenous insulin requirement; LDH, lactate dehydrogenase; IU, international units.
Baseline vs. follow-up sitagliptin: *P < 0.05; ***P < 0.001.
Baseline vs. follow-up standard of care: ^P < 0.05; ^^^P < 0.001.
- Table 3
Multivariable analysis of factors associated with mortality in patients with type 2 diabetes and COVID-19 treated with sitagliptin or with standard-of-care therapy
OR (95% CI) P value Treatment with sitagliptin 0.23 (0.12–0.46) 0.0001 Sex (male) 1.05 (0.51–2.16) 0.88 Age (years) 1.07 (1.04–1.11) 0.0001 Cancer 1.74 (0.78–3.88) 0.17 Cardiovascular disease 2.5 (1.30–4.81) 0.006 Chronic kidney disease 1.12 (0.54–2.35) 0.74 Use of hydroxychloroquine 1.47 (0.55–3.87) 0.43 Use of antiviral agents 0.91 (0.44–1.85) 0.79 - Table 4
HRs calculated for the secondary clinical outcomes (need for intensive care unit, mechanical ventilation, and ECMO)
Secondary end points N at risk (N with end point), sitagliptin vs. standard of care HRs (95% CI) for sitagliptin vs. standard of care P value Intensive care 118 (15) vs. 102 (25) 0.51 (0.27–0.95) 0.03 Mechanical ventilation 118 (6) vs. 102 (17) 0.27 (0.11–0.62) 0.003 ECMO 118 (8) vs. 102 (7) 1.15 (0.41–3.17) 0.77
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