Background: Although insulin treatment confers short-term benefit in cystic fibrosis-related diabetes (CFRD), few studies have compared its long-term effect on the clinical outcome. Objectives: In this study, we aimed to investigate the long-term impact of insulin treatment on pulmonary function, nutritional status and hospital admissions in patients with CFRD. Methods: We reviewed pulmonary function, body mass index (BMI) and hospital admissions 5 years before and 3 years after insulin therapy in 42 adult CFRD patients. Results: Prior to treatment, over a period of 5 years, the annual rate of change in forced expiratory volume in 1 s (FEV₁) was –3.2%, forced vital capacity (FVC) –2.5%, and BMI –0.07%. At treatment of CFRD (baseline), the mean FEV₁ was 51.6% predicted (range 24–96), FVC 66.4% (range 29–103) and BMI 19.5 (range 15.3–29.5). At 3 months following insulin treatment, there was a significant improvement in all parameters, which was maintained at 1 year for FEV₁ (55.1%; p < 0.002), 2 years for FVC (72.1%; p < 0.01) and at 3 years for BMI (20.4%; p < 0.002). After 3 months, FEV₁ declined at a rate similar to that before treatment (–3.2 vs. –3.1% per year; p = 0.77), such that the mean FEV₁ after treatment returned to pretreatment baseline values at 34 months. There was no difference in the number of hospital admissions with insulin treatment. Conclusions: Insulin enhances the nutritional state and temporarily improves pulmonary function in CFRD patients, on average delaying the decline in FEV₁ by 34 months.