Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program...

Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials.

The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV₁/FVC <70%), restrictive pattern (FVC < LLN and FEV₁/FVC ≥70%), preserved ratio impaired spirometry (PRISm: FEV₁ <80% predicted, FEV₁/FVC ≥70%) and symptoms (COPD Assessment Test [CAT] score ≥10).

The 1888 participants with spirometry were a mean (±SD) age of 68.2 ± 9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0 ± 0.8 years. The mean FEV₁ was 2.14 ± 0.60 L, FVC 2.74 ± 0.74 L, FEV₁/FVC 78.4 ± 6.4%, mean BMI was 32.4 ± 6.7 kg/m² and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV₁, FVC or FEV₁/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group.

In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.