Evaluation for clinical benefit of metformin in patients with idiopathic pulmonary fibrosis and type 2 diabetes mellitus: a national claims-based cohort analysis

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high morbidity and limited treatment options. Type 2 diabetes mellitus (T2DM) is a common comorbid illness among patients with IPF and is often treated with metformin, the first-line agent in the management of T2DM. There is growing evidence demonstrating metformin’s anti-fibrotic properties; however, there is little real-world clinical data regarding its potential effectiveness in IPF. This study aims to evaluate the clinical benefit of metformin in patients with IPF and T2DM. Methods This nationwide cohort study used de-identified administrative claims data from OptumLabs® Data Warehouse to identify 3599 adults with IPF and concomitant T2DM between January 1, 2014 and June 30, 2019. Two cohorts were created: a cohort treated with metformin (n = 1377) and a cohort not treated with metformin (n = 2222). A final 1:1 propensity score-matched cohort compared 1100 patients with IPF and T2DM receiving metformin to those with both diagnoses but not receiving metformin; matching accounted for age, sex, race/ethnicity, residence region, year, medications, oxygen use, smoking status, healthcare use, and comorbidities. Outcomes were all-cause mortality (primary) and hospitalizations (secondary). Results Among 2200 patients with IPF and T2DM included in this matched analysis, metformin therapy was associated with a reduction in all-cause mortality (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.36–0.58; p < 0.001) and hospitalizations (HR, 0.82; 95% CI, 0.72–0.93; p = 0.003) compared to patients not receiving metformin. Conclusions Among patients with IPF and T2DM, metformin therapy may be associated with improved clinical outcomes. However, further investigation with randomized clinical trials is necessary prior to metformin’s broad implementation in the clinical management of IPF.

Effectiveness and mechanism of metformin in animal models of pulmonary fibrosis: A preclinical systematic review and meta-analysis

“…However, both studies were limited by their small sample sizes ( n = 28 and n = 71). In contrast, a recent retrospective cohort study that included 3,599 patients with IPF and T2DM showed a significant 54% reduction in all-cause mortality with MET treatment ( Teague et al, 2022 ). This effect was substantially better than that of the current anti-fibrotic agents (23%) ( Dempsey et al, 2019 ).…”

“…However, it is worth noting that this study observed the effect of MET in patients with PF and T2DM, and there is insufficient evidence of a direct causal relationship between MET and PF. In addition to its anti-fibrotic effect, MET also has cardioprotective and hypoglycemic effects ( Holman et al, 2008 ; Roumie et al, 2012 ), which may be responsible for reducing mortality in patients with PF and T2DM ( Teague et al, 2022 ). Therefore, further clinical trials are required.…”

“…There is a lack of specific therapeutic drugs for the treatment of PF. Pirfenidone and nintedanib ( Raghu et al, 2015 ; Teague et al, 2022 ), approved for the treatment of PF, have been shown to reduce the decline in forced vital capacity (FVC) and deterioration in the acute phase in patients with IPF ( Richeldi et al, 2011 ; King et al, 2014 ). However, current studies show that these two drugs do not cure or reverse PF ( Wollin et al, 2015 ); they can only prevent the development or further progression of PF.…”

“…To date, no drug has been able to reverse already established PF ( Dos Santos et al, 2018 ). Only a few patients can afford pirfenidone and nintedanib because they are expensive ( Teague et al, 2022 ). Moreover, the diagnosis of IPF and the adverse effects of these drugs are uncertain ( Maher et al, 2018 ; Maher and Strek, 2019 ).…”

Role of MicroRNAs in Signaling Pathways Associated with the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Focus on Epithelial-Mesenchymal Transition

“…However, and in spite of all advances in our comprehension of idiopathic pulmonary fibrosis, current therapeutic options still have great limitations [ 121 , 122 , 123 ]. Therefore, the search, analysis, and discussion of new treatment options are necessary.…”