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Glucose-Lowering Medications and COVID-19 Outcomes in Patients with Diabetes

Jul 25, 2020
 
Editor: Steve Freed, R.PH., CDE

Author: Melinda Rodriguez, PharmD Candidate 2021, Lake Erie College of Osteopathic Medicine – L|E|C|O|M School of Pharmacy

What factors and medications affect COVID-19 complications and mortality in patients with diabetes?

The spread of COVID-19 has caused a rapidly growing health crisis worldwide. Patients with comorbidities are more likely to experience worse outcomes than those without. Diabetes is one of the most frequently reported comorbid conditions in patients with COVID-19. Although incidence and mortality rates of infected patients with diabetes vary by location, we know that patients with diabetes tend to develop more severe forms of the disease, requiring intensive care or mechanical ventilation, than those with other underlying conditions. While the number of investigations into COVID-19 cases has skyrocketed in recent months, much is still unknown regarding risk factors, prognosis, and the effects of glucose-lowering medications in the diabetic subset of the COVID-19 patient population. A new study in Diabetes Care describes the clinical characteristics of, and outcomes in, patients that are COVID-19 positive with diabetes, and their outcomes’ association with glucose-lowering medications.

The retrospective study included patients aged 15-99 years who were admitted to a hospital in Wuhan, China, from January to March 2020 with a diagnosis of COVID-19. Of the 904 patients identified, 120 patients had type 2 diabetes mellitus (T2DM), 1 patient had type 1 diabetes mellitus (T1DM), 1 had gestational diabetes, and 14 were not diagnosed before admission. Using electronic medical records, experienced clinicians gathered information regarding epidemiological, demographic, clinical, laboratory, treatment-related, and outcome-related data utilizing a standardized data collection form. Patients underwent C.T. chest imaging and standard laboratory monitoring, including coagulation tests, liver and renal function, creatine kinase, lactate dehydrogenase, and electrolytes.

Of all the patients admitted with a diagnosis of COVID-19, 64% presented with fever, 49% reported cough, and 23% experienced fatigue. Hypertension was the most common comorbidity (30%), followed by diabetes (15%). Patients with diabetes had more comorbidities, of which the most frequently reported were hypertension, cardiovascular disease, and nervous system disease. Roughly half of the patients progressed to severe or critical conditions during hospitalization, and 10% of patients deceased in hospital. Univariate logistic regression analysis showed increased odds of in-hospital death or poor prognosis in patients with COVID-19 and diabetes (death: OR 2.51 [95% CI 1.53, 4.13], prognosis: OR 2.21 [95% CI 1.50, 3.26]; both P<0.001). Those with diabetes were much more likely to have worse prognosis and progress to severe or critical condition, as was apparent when comparing the average length of stay of patients with and without diabetes (19 and 26 days, respectively). Multivariate logistic regression showed that patients with diabetes also had increased odds of death if they were older, had elevated C-reactive protein (CRP), or had low albumin.

When characterizing patients with COVID-19 and diabetes who had available glucose-lowering medication histories, researchers found different laboratory indices between those that used insulin and those that did not. These included lower albumin, higher infection-related indices (CRP, procalcitonin, and ESR), and higher HbA1c and blood glucose on admission. Compared with non-insulin users, those that did use insulin had a higher risk of poor prognosis (OR 3.58 [95% CI 1.37, 9.35]; P<0.009). Metformin users showed lower urea and interleukin-6 (IL-6) and higher albumin levels on admission than non-metformin users. Those on secretagogues had less malignant initial indices, including significantly lower white blood cell counts, and fewer neutrophils. Lower creatine kinase, CRP, and IL-6 levels were also seen in those who use secretagogues. The laboratory findings and outcomes for patients using a-glycosidase or DPP-4 inhibitors were no different from those of respective non-users. Finally, multivariable regression analysis did not indicate any association between in-hospital death and glucose-lowering medications (metformin, insulin, a-glycosidase, secretagogues, or DPP-4 inhibitors).

Of note, 71 of the 136 patients with diabetes had comorbid hypertension and available blood pressure-lowering medication history. Thirty-two of them used an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Previously, these medications were reported to increase the expression of ACE2, a crucial target of SARS-CoV-2. However, no significant difference was observed between the clinical outcomes of the ACEI/ARB users and the ACEI/ARB non-users.

In summary, COVID-19 infected patients with diabetes showed aggravated kidney injury and severe inflammatory response. There was a significantly higher percentage of comorbid diseases in patients with diabetes, which may contribute to this patient population’s poor prognosis. One possible index to consider is CRP, which may help identify patients with diabetes who are at higher risk of dying during hospitalization. Older patients with diabetes may also be prone to death related to COVID-19. Special attention must be paid to patients with diabetes and COVID-19 who use insulin as these patients showed a worse prognosis. Finally, there was no significant association between any glucose-lowering agent, ACEI, or ARB.

Practice Pearls:

  • Patients with diabetes that have COVID-19 may be at higher risk of poor prognosis if they use insulin than those that do not use insulin.
  • In this study, there was no association between any of the glucose-lowering medications and in-hospital death.
  • One possible index to consider is CRP, which may help identify patients with diabetes who are at higher risk of dying during hospitalization.

 

Williams DM, Nawaz, Evans M. Diabetes and Novel Coronavirus Infection: Implications for Treatment [published online, 2020 July 13]. Diabetes Ther.2020;1-10.doi:10.1007/s13300-020-00858-2

 

Melinda Rodriguez, PharmD Candidate 2021, Lake Erie College of Osteopathic Medicine – L|E|C|O|M School of Pharmacy

 

 

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