Reduced mortality from lower respiratory tract disease in adult diabetic patients treated with metformin

Abstract

Background and objective: Chronic lower respiratory diseases (CLRD) increase the risk of type 2 diabetes, which in turn may worsen lung function. Metformin, a common antidiabetic with anti-inflammatory and antioxidant properties, may improve respiratory outcomes. Therefore, we examined the association of metformin use with the risk of mortality from CLRD. Methods: We analysed data from the National Health and Nutrition Examination Survey during 1988-1994 and 1999-2010 for participants aged 40 years or older who had diabetes and were followed up for mortality through 2011. Information on prescription medicine was collected at baseline and CLRD-related mortality during follow-up was defined using the 10th Revision of the International Classification of Diseases (ICD-10). Cox proportional hazards modelling was used to determine the mortality hazard ratio (HR) associated with metformin use, adjusting for relevant covariates. Results: A total of 5266 participants with a median follow-up of 6.1 years were included. The prevalence of metformin use was 31.9% and 1869 participants died during follow-up, including 72 of CLRD. In the adjusted Cox proportional regression analysis, metformin was associated with a decreased risk of CLRD mortality in the overall population (HR: 0.39, 95% CI: 0.15-0.99) and among participants with baseline CLRD (HR: 0.30, 95% CI: 0.10-0.93), after adjusting for age, gender, race/ethnicity, cigarette smoking, body mass index, current asthma and chronic obstructive pulmonary disease (COPD), insulin and other diabetic medications, and glycohaemoglobin level. We found no association between other antidiabetic medications and CLRD mortality. Conclusion: In this sample representative of the U.S. population, metformin was associated with lower CLRD mortality in adults with diabetes.This population-based prospective cohort demonstrated that metformin use in type 2 diabetes was associated with a significant decrease in the risk of mortality from chronic lower respiratory disease (CLRD) after adjusting for relevant covariates. This reduction was even more pronounced among subjects with CLRD at baseline.

Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review

“…A retrospective observational study by Bode et al [45] from 88 hospitals in USA involving 570 patients found a significantly higher mortality rate (28.8% vs. 6.2%, p < 0.001) in patients with diabetes (HbA1c 6.5%) and/or uncontrolled hyperglycemia (defined as 2 blood glucose value >180 mg/dL within any 24-hour period), compared to patients without diabetes or hyperglycemia. Moreover, amongst the patients who survived (n = 493), the length of stay in hospital was significantly longer in patients with diabetes and uncontrolled hyperglycemia, compared to patients without diabetes or uncontrolled hyperglycemia 56; in controlled vs. uncontrolled diabetes, respectively), compared to the cohorts without diabetes even after the full adjustment of confounding factors [46]. In a large retrospective study (n = 7337), Zhu et al reported a significant 49% relative increase in all-cause mortality (HR 1.49; 95% CI, 1.13-1.96; p = 0.005) in patients with diabetes (n = 810), compared to the groups without diabetes (n = 6385) and COVID-19, even after the adjustment of multiple confounding factors [42].…”

The Role of Adipocytes and Adipocyte‐Like Cells in the Severity of COVID‐19 Infections

“…Induction of PPARγ leads to an effective reduction of tissue and organ fibrotic disease, including pulmonary fibrosis (15). This effect is at least partially mediated by adiponectin (16). The level of adiponectin in circulation is inversely proportional to adipose mass, is significantly reduced in patients with systemic sclerosis, and is negatively correlated with severity of this disease (17).…”

Diabetes and COVID-19: evidence, current status and unanswered research questions

“…The precise effect of treatment with various oral antihyperglycaemic agents on the severity of COVID-19 is not known, though there are some theoretical considerations. Metformin has shown modest benefits in lower respiratory tract infections and pulmonary tuberculosis [16], though gastrointestinal tolerability in sick patients is of concern. Thiazolidinediones have been shown to increase ACE2 levels [17].…”