Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

Carrie L Pistenmaa; Lindsay Doherty; Emilia A Hermann; Angela L Brown; Dana Dabelea; Fernando Holguin; Karol Watson; William C Knowler; Marinella Temprosa; R Graham Barr; DPP Research Group

doi:10.1016/j.rmed.2026.109077

PubMed · 42551713

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

Carrie L Pistenmaa·Lindsay Doherty·Emilia A Hermann·Angela L Brown·Dana Dabelea·Fernando Holguin·Karol Watson·William C Knowler·Marinella Temprosa·R Graham Barr·DPP Research Group

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Abstract

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

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Humans Metformin Female Spirometry Hypoglycemic Agents Male Aged Diabetes Mellitus, Type 2 Middle Aged Life Style Forced Expiratory Volume Vital Capacity Respiratory Function Tests Treatment Outcome Journal Article Randomized Controlled Trial

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Carrie L Pistenmaa, Lindsay Doherty, Emilia A Hermann, Angela L Brown, Dana Dabelea, Fernando Holguin, Karol Watson, William C Knowler, Marinella Temprosa, R Graham Barr, DPP Research Group. 2026-08-04. Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).. https://doi.org/10.1016/j.rmed.2026.109077

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