4 / 16
52nd annual meeting of the
European Association
for the Study of Diabetes
12–16 SEPTEMBER 2016 • MUNICH, GERMANY
Myocardial dysfunction in diabetes,
pregnancy outcomes of women with
gestational diabetes, keeping HbA1c at goal,
and overuse of acetylsalicylic acid in diabetes
were just a handful of the many scientific
and clinical presentations at the 52nd annual
meeting of the European Association for the
Study of Diabetes (EASD). The PracticeUpdate
Editorial Team reports.
Though liraglutide + insulin is effective in type 1
diabetes, a high hypoglycaemia rate limits its use
Liraglutide 1.8 and 1.2 mg, as an adjunct to insulin, has been shown to lead to greater reductions in haemoglobin
A1c, body weight, and total insulin dose than placebo. Higher rates of symptomatic hypoglycaemia limit its utility
for a broad population of patients with type 1 diabetes, however.
T
his outcome of ADJUNCT ONETM,
a 52-week double-blind, multinational
treat-to-target trial in adults with type
1 diabetes in suboptimal glycaemic control
(haemoglobinA1c 7–10%) was reported at the
EASD 2016 meeting.
Chantal Mathieu, MD, of Katholieke Uni-
versiteit, Leuven, Belgium, and colleagues set
out to determine whether adjunct treatment
with liraglutide, a glucagon-like peptide-1
analog, improves glycaemic control and re-
duces insulin requirements and body weight
in type 1 diabetes.
Subjects (n = 1398) were randomised 3:1
to once-daily subcutaneous injections of lira-
glutide (1.8, 1.2, or 0.6 mg) or placebo as an
adjunct to insulin. Primary endpoints were
change in haemoglobin A1c, fasting body
weight, and total insulin dose. The secondary
endpoint was the incidence of symptomatic
hypoglycaemic episodes.
At baseline, mean age, type 1 diabetes
duration, haemoglobin A1c, and body weight
were 44 years, 21 years, 8.2%, and 86.2 kg,
respectively. Fifty-two percent of subjects were
women, 28% were on continuous subcutane-
ous insulin treatment, 7% had severe hypogly-
caemia in the past year, 6% had hypoglycaemic
unawareness, and 17% had a fasting C-peptide
≥
0.03 nmoL/L.
HaemoglobinA1c was reduced 0.34–0.54%
across groups at week 52. Despite the treat-
to-target design, reductions in haemoglobin
A1c were significantly larger for liraglutide
1.8 and 1.2 mg than for placebo (estimated
treatment differences 95% CI 1.8 mg: –0.20%
[–0.32; –0.07], 1.2 mg: –0.15% [–0.27; –0.03],
0.6 mg: –0.09% [–0.21; 0.03]).
Reductions in body weight were significantly
larger for all liraglutide groups than for placebo
(estimated treatment differences and 95% CI
1.8 mg: –4.9 kg [–5.7; –4.2], 1.2 mg: –3.6 kg
[–4.3; –2.8], 0.6 mg: –2.2 kg [–2.9; –1.5]).
Reductions in total insulin dose were sig-
nificantly larger for liraglutide 1.8 and 1.2 mg
than for placebo (estimated treatment ratios
and 95% confidence intervals 1.8 mg: 0.92
[0.88; 0.96], 1.2 mg: 0.95 (0.91; 0.99), 0.6 mg:
1.00 [0.96; 1.04]).
Significantly more symptomatic hypogly-
cemic episodes (severe or plasma glucose
<56 mg/dL and hypoglycaemic symptoms)
were seen for liraglutide 1.8 and 1.2 mg than
for placebo (estimated rate ratios and 95% CI
1.8 mg: 1.31 [1.07; 1.59], 1.2 mg: 1.27 [1.03;
1.55], 0.6 mg: 1.17 [0.97; 1.43]).
No significant differences were observed for
severe hypoglycaemic episodes (1.8 mg [45],
1.2 mg [31], 0.6 mg [40], placebo [57]). Sig-
nificantly more hyperglycaemic episodes with
ketosis >1.5 mmoL/L were seen with 1.8 mg
[77] than for placebo [37], but not for 1.2 mg
[44] or 0.6 mg [54]. Eight diabetic ketoacido-
sis episodes occurred (1.8 mg [3], 1.2 mg [1],
0.6 mg [4], placebo [0]). The most frequently
reported adverse events with liraglutide were
nausea and vomiting.
Dr Mathieu concluded that liraglutide 1.8
and 1.2 mg, as an adjunct to insulin, led to
greater reductions in haemoglobin A1c, body
weight, and total insulin dose than placebo.
Higher rates of symptomatic hypoglycaemia
limit its clinical utility for a broad population
of patients with type 1 diabetes, however.
She added, “There might still be a role for
glucagon-like peptide 1 receptor agonists as
adjunct therapies in people with type 1 dia-
betes. In real life, the benefits on weight and
haemoglobin A1c outweigh the risk of hypo-
glycaemia. And in real life, doses of insulin can
be adapted more rapidly to glycaemia than in
a clinical trial.”
The benefits on weight and
haemoglobin A1c outweigh the risk
of hypoglycaemia. And in real life,
doses of insulin can be adapted
more rapidly to glycaemia than in a
clinical trial.
CONFERENCE COVERAGE
PRACTICEUPDATE ENDOCRINOLOGY
4