The efficacy and safety of liraglutide as adjunct therapy to insulin in the treatment of type 1 diabetes;
A 52-week randomised, treat-to-target, placebo-controlled, double-blinded, parallelgroup, multinational, multi-centre trial

Glycaemic control in subjects with type 1 diabetes is often suboptimal.
Liraglutide is an analogue of the naturally occurring human hormone GLP-1, and
is suitable for once daily administration.
Small scale studies and case reports in subjects with type 1 diabetes indicate
that treatment with a GLP-1 receptor agonist, such as liraglutide as adjunct to
insulin, may result in:
a) improvement in glycaemic control through reduction in fasting and
postprandial hyperglycaemia,
in part due to inhibition of postprandial hyperglucagonaemia,
b) reduction in glucose excursions,
c) reduction in episodes of hypoglycaemia,
d) reduction in insulin requirements and
e) a weight benefit
The clinical circumstances of insulin treatment in type 1 diabetes not being
optimal imply that new efforts to improve treatment for type 1 diabetes
subjects are needed. The rationale for this trial in type 1 diabetes is to
investigate liraglutide therapy as adjunct to insulin therapy in subjects,
where current insulin treatment does not provide adequate and satisfactory
glycaemic control, and where subjects due to fear of hypoglycaemia and/or
weight gain refrain from optimising their insulin treatment.

For more detailed information please refer to chapter 3 of the trial protocol
(p 23-28)

To confirm the efficacy of liraglutide as adjunct to insulin treatment on
glycaemic control, and to
confirm the superiority of liraglutide treatment compared to placebo, both
adjunct to insulin
treatment, with regard to reduction in daily insulin dose and body weight loss,
after 52 weeks of
treatment in subjects with established type 1 diabetes with inappropriate
glycaemic control.

The trial is a randomised, placebo-controlled, double-blinded, parallel-group,
multinational, multicentre
trial designed for evaluation of the efficacy and safety of adding liraglutide
(0.6 mg, or 1.2
mg or 1.8 mg liraglutide) versus placebo to insulin treatment in subjects with
type 1 diabetes during
52 weeks of treatment, in a treat-to-target (T-T-T) design.
After 2 weeks of screening, subjects will be randomised in a 3:3:3:1:1:1 manner
to liraglutide
treatment (0.6 mg, 1.2 mg or 1.8 mg), or liraglutide placebo both adjunct to
insulin treatment.
The total trial duration per subject is approximately 58 weeks and consists of
a 2-week screening
period, a treatment period after randomisation with a dose initiation and dose
escalation period of 2 to 4 weeks (dependent on randomised dose of liraglutide/
liraglutide placebo adjunct to insulin
treatment), a maintenance period 48-52 weeks (dependent on randomised dose of
liraglutide/
liraglutide placebo adjunct to insulin treatment), and 4-week follow-up period.
Subjects will be in close and frequent contact, both by phone and site visits
to the clinic during the
dose escalation part of the trial. During the maintenance part of the trial the
subjects will have site
visits every four to six weeks.

During the trial the subjects will follow their regular insulin treatment.

For this trial the following trial products will be provided:
* Liraglutide 6.0 mg/mL, in a 3 mL pre-filled pen injector for subcutaneous
(s.c.) injection
* Liraglutide placebo 3 mL in a pre-filled pen injector for s.c. injection

All subjects will initiate liraglutide/ liraglutide placebo treatment at 0.6 mg
on the day of
randomisation (Visit 2).
Subjects randomised to the 0.6 mg arms will remain on this dose throughout the
study (52 weeks).
Subjects randomised to the 1.2 mg and 1.8 mg arms will increase the dose to 1.2
mg after 2 weeks.
Subjects randomised to the 1.2 mg arms will remain on this dose for 50 weeks.
Subjects randomised to the 1.8 mg dose group will increase the dose to 1.8 mg 4
weeks after
randomisation and remain on this dose for 48 weeks.

Subjects are requested to visit the trial site 15 times and attend
telephonecalls with the site staff 17-23 times . This could be perceived as a
burden.
Bloodsampling is part of standard diabetes care. Due to the higher frequency
the subjects may perceive some inconvenience.
12 x venapunction, of which 5x fasting
4-point bloodglucoseprofile (27x)
7-point bloodglucoseprofile on day of start and dose increase trialmedication
and the following 3 days (4 to 12x, depending on randomisation).
9-point bloodglucoseprofile (total 4x)
Hypoglycamia could occur. Therefore the subject is closely followed at start of
treatment and at dose increase, in order to adjust the insulin dose to the
subjects individual needs.
There have been few reported events of acute pancreatitis. Subjects will be
informed of the characteristic symptoms and lipase, amylase and calcitonine
will be monitored closely during the trial.
In the early part of treatment gastrointestinal adverse events may occur. This
may induce loss of body fluid and could lead to dehydration. Subjects are
requested explicitly to take in plenty of fluids.
Physical examination, pregnancy test and funduscopy at trial start and end.
Subjects are requested to complete questionnaires on quality of life 3 times
during the trial and are requested to complete diaries (concerning self
measured plasmaglucose, insuline dose, comcomittant illness and medication).