A placebo-controlled trial of insulin therapy with or without adjuvant metformin in patients with Cystic Fibrosis-Related Diabetes

Diabetes is a major co-morbidity in patients with Cystic Fibrosis (CF) with a
prevalence of 31% in our adult patient population. Cystic fibrosis-related
diabetes (CFRD) consists of both insulin deficiency and insulin resistance and
is increasing with age. It is associated with deterioration in overall clinical
status and shorter life expectancy, presumably due to a higher susceptibility
to develop pulmonary infections. Therefore it is important to aim towards
perfect glycaemic control.
The recommended treatment in CFRD is insulin therapy. Still the diabetes is
difficult to control due to the fluctuating insulin resistance during pulmonary
exacerbations. We hypothesize that by adding an oral glucose-lowering agent to
insulin therapy a better overall management of CFRD can be accomplished.

Investigate the effect of adjuvant metformin therapy on insulin need and on
glycaemic control in CFRD patients.

Prospective randomised double-blind crossover placebo-controlled study.

All patients will be randomised for either first receiving adjuvant metformin
or first receiving placebo during the first therapy period. The metformin
dosage will be weight-dependant. For the second therapy period patients will
interchange to the other therapy regimen, either metformin or placebo.

The total study period for each subject comprises 32 weeks, i.e. a 4-weeks
run-in period, a 12-weeks treatment period, a 4-weeks wash-out period and the
second 12-weeks treatment period. During the study the patients will visit the
outpatient clinic with a minimum of 9 times, spread out over the total study
period. At each visit, patients are fasting in order to give blood. They will
undergo physical examination and will be questioned about their present
clinical status. During the two treatment periods, patients have to take either
the metformin tablets or placebo tablets with a maximum of 4 tablets a day.
During the study patients are asked to do regular glucose serial
self-monitoring blood glucose testing and to keep up a diary with their glucose
levels and insulin usage. A continous glucose monitoring for three days will be
performed during both periods. At the end of both treatment periods patients
are asked to make a standardized quality of life questionnaire for CF patients.