Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was first reported in December 2019 [1].
Type 2 diabetes (T2D) is an important risk factor for mortality and poor prognosis in COVID-19 patients [2, 3]. Metformin and insulin were suggested to have an impact on the outcomes. However, opposing viewpoints continue to be expressed. In this study, we sought to perform a retrospective analysis of metformin and insulin effects in COVID-19 patients with T2D.
This was a retrospective study conducted at the Transcarpathian Regional Clinical Infectious Diseases Hospital (Uzhhorod, Ukraine). We used retrospective patient data collected from medical records available from the e-health information system, which included all adult patients admitted from January 2021 to March 2022. Confirmation of the diagnosis of COVID-19 was carried out by the PCR method. In-hospital confirmed COVID-19 patients were divided into T2D and non-diabetes. T2D was defined according to the World Health Organization diagnostic criteria [4].
The results are reported as the median [interquartile range (IQR)] for baseline laboratory indices and the number [percentage] for categorical variables. The classification variable was represented as a count (%). Continuous variables with normal distribution were presented as mean [standard deviation (SD)]. Differences in parameters among groups were analyzed using ANOVA for continuous variables, and the χ2 test was used for categorical variables. P-value ≤ 0.05 was considered to indicate statistical significance.
Among the 145 confirmed patients, the median age was 62.66 ± 12.96, and 66 patients (45.5%) were male. Patients with T2DM were older than patients without T2D 53.66 ± 13.37 vs. 67.00 ± 7.70 (p = < 0.001). Among these 80 diabetic patients, all had T2D.
During hospitalization, 25 cases with T2D had metformin. Patients had in-hospital metformin with a median of 1.0 g per day (IQR 0.55–1.52). In patients who took metformin, the level of C-reactive protein (CRP) was significantly lower than in patients who did not take metformin [24 mg/L (IQR 15–58) vs. 52 mg/L, (IQR 22–121), p = 0.046] (Tab. 1).
Characteristics |
Non-metformin |
Metformin |
P-value |
Non-insulin |
Insulin |
P-value |
Age [years] |
58.67 ± 10.81 |
60.80 ± 12.56 |
0.518 |
52.67 ± 8.81 |
67.8 ± 9.26 |
0.038 |
Gender (M, %) |
7 (43.7 %) |
12 (48 %) |
0.657 |
6 (60 %) |
17 (48.5 %) |
|
Comorbidities (n, %) |
||||||
Hypertension, N (%) |
7 (43.7%) |
7 (28%) |
0.257 |
3 (30%) |
9 (25.7%) |
0.436 |
Cardiovascular disease, N (%) |
2 (12.5%) |
4 (16%) |
0.368 |
1 (10%) |
5 (14.2%) |
0.813 |
Chronic kidney disease, N (%) |
7 (43.7%) |
7 (28%) |
0.537 |
4 (40%) |
10 (28.5%) |
0.251 |
Baseline laboratory indices |
||||||
Blood glucose [mmol/L] |
7 (5–14) |
10 (8–14) |
0.014 |
5 (4–8) |
14 (9–15) |
< 0.001 |
White blood cells [× 109/L] |
8 (6–12) |
9 (6–10) |
0.463 |
7 (5–11) |
9 (7–12) |
0.082 |
Lymphocytes [× 109/L] |
1 (1–1) |
1 (1–1) |
0.666 |
1 (1–2) |
1 (1–1) |
0.430 |
Monocytes [× 109/L] |
0 (0–0) |
0 (0–0) |
0.040 |
0 (0–0) |
0 (0–0) |
0.368 |
Neutrophils [× 109/L] |
7 (5–11) |
7 (4–9) |
0.315 |
6 (4–8) |
9 (6–11) |
0.022 |
Serum creatinine [μmol/L] |
102 (86–119) |
105 (90–124) |
0.644 |
102 (86–118) |
102 (87–127) |
0.647 |
C-reactive protein [mg/L] |
52 (22–121) |
24 (15–58) |
0.046 |
40 (16–104) |
43 (18–100) |
0.846 |
D-dimer [μg/mL] |
1 (0–3) |
1 (0–3) |
0.544 |
1 (0–3) |
2 (1–3) |
0.181 |
Procalcitonin [ng/mL] |
0 (0–1) |
0 (0–1) |
0.660 |
0 (0–1) |
0 (0–1) |
0.340 |
COVID-19 treatment protocols |
||||||
Antibiotics (n, %) |
13 (81.2%) |
14 (56%) |
0.486 |
8 (80%) |
25 (71.4%) |
0.587 |
After admission, 35 patients received insulin. In-hospital insulin users with a median of 35.0 units per day (IQR 28.2–50.3). Higher blood glucose levels [14 mmol/L, (IQR 9–15) vs. 5 mmol/L (IQR 4–8), p = < 0.001] were seen in insulin users. Patients in the insulin group had higher white blood cell (WBC) count [9 × 109/L, (IQR 7–12) vs. 7 × 109/L (IQR 5–11), p = 0.082] and neutrophil levels than those of the non-insulin group [9 × 109/L, (IQR 6 –11) vs. 6 × 109/L (IQR 4–8), p = 0.022] with no difference in general characteristics and other laboratory indices.
In this study, we found that metformin use prior to admission was linked to declining CRP levels among COVID-19 patients with T2D. In the long run, metformin may be more advantageous than insulin for COVID-19 patients with T2D. To confirm the current findings, more research is required.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
None declared.