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The analysis demonstrated
the difficulty of maintaining
haemoglobin A1c to goal over
3 years, even in a clinical trial
setting.
>6
The findings support the concept that
(micro)vascular structural brain damage
precedes the clinical diagnosis of type 2
diabetes andmay contribute to the
cerebral complications of prediabetes and
type 2 diabetes.
>8
Platelets frompoorly controlled type 2
diabetic patients lost not only their ability
to protect against ischaemia/reperfusion
injury but also induced an increase of
infarct size and lactate dehydrogenase
release, amarker of necrosis.
>9
Pregnancy outcomes of women with gestational diabetes are worse but
most differences are due to higher body weight
Though the pregnancy outcomes of women with World Health Organization (WHO) classified gestational diabetes
have been shown to be worse than those with normal glucose tolerance, most of the differences were explained
by the higher body weight of these women, finds a retrospective database analysis.
A.G. Tabak, MD, of University College
London, UK, and Semmelweis University,
Budapest, Hungary, explained that the WHO
issued new recommendations for the diagnosis
of gestational diabetes mellitus in 2013. The
new diagnostic criteria approximately double
the prevalence of gestational diabetes versus
the previous WHO recommendation. Several
professional bodies (including the National
Institute for Health and Care Excellence
[NICE]) recommended less stringent cutoff
values to limit the prevalence of gestational
diabetes.
Given that the diagnosis of gestational
diabetes has been based on the WHO-1999
criteria in the last decade in Hungary, a large
proportion of women currently considered to
have gestational diabetes remained untreated.
Dr Tabak said, “The WHO 2013 diagnostic
recommendation of gestational diabetes is based
on observational findings of the multinational
Hyperglycemia and Adverse Pregnancy Out-
comes (HAPO) study. These recommendations
lack the support of randomised clinical trials.”
He added, “We tried to fill this evidence gap
by providing retrospective analytic data on the
outcomes of the mildest forms of gestational
diabetes.”
Dr Tabak and colleagues set out to compare
pregnancy outcomes of women with untreated
gestational diabetes (according to WHO 2013,
WHO–Gestational Diabetes Mellitus and
NICE 2015, and NICE–Gestational Diabe-
tes Mellitus) and women with normal glucose
tolerance.
During a universal screening program in
western Hungary, 4828 pregnant women had
a 75 g oral glucose tolerance test using three-
point glucose determinations in 4 years. Based
on these oral glucose tolerance tests, 696
(14.4%) WHO–Gestational Diabetes Mellitus
and 478 (9.9%) NICE–Gestational Diabetes
Mellitus cases were diagnosed retrospectively.
A total of 251 women who were treated for
gestational diabetes were excluded from the
analysis.
Untreated women with gestational diabetes
were older and had higher fasting 60-minute,
and 120-minute blood glucose, and blood
pressure. No difference in marital status
or education was found. Women with ges-
tational diabetes had higher body weight,
though weight gain was similar in all groups
(13 kg). WHO–Gestational Diabetes Mellitus
newborns had a higher birthweight (144 ±
31 g), Newborns of women who had NICE–
Gestational Diabetes Mellitus were of similar
birthweight (66 ± 43 g) to controls.
Several important outcomes were more
frequent in groups classified as having ges-
tational diabetes by either criterion including
hypertension during pregnancy (see box).
No difference in the risk of preeclampsia and
malformations was found. After adjustment
for the mothers’ weight at delivery, women with
WHO-classified gestational diabetes mellitus
had similar outcomes as women with normal
glucose tolerance. While for the group with
NICE-classified gestational diabetes mellitus,
induced delivery and acute caesarean section
remained more frequent.
Dr Tabak concluded that, though the preg-
nancy outcomes of women with WHO-classi-
fied gestational diabetes mellitus were worse
than those of women with normal glucose toler-
ance, most of the differences were explained by
the higher body weight of these women.
Some outcomes remained worse for women
with NICE-classified gestational diabetes
mellitus, even after taking into account the
weight difference between women with
NICE-classified gestational diabetes mellitus
and those with normal glucose tolerance.
These outcomes support use of the less strin-
gent cutoff values recommended by NICE.
The data suggests that treatment focused
on weight gain during pregnancy might be
enough the improve outcomes of these ‘mild’
gestational diabetes cases (WHO-classified
gestational diabetes mellitus).
Dr Tabak said, “The finding that the moth-
er’s weight explains some of the differences in
outcomes is hardly surprising. The real prob-
lem is to find the right cutoff, where the role
of maternal weight becomes less important
than that of glycaemia. Our study offers some
direction to this problem, but the final answers
should come from randomised trials.”
Patients who switch from sitagliptin to liraglutide
experience better glycaemic control, weight loss, and
reduced SBP and hypoglycaemic episodes
By switching from sitagliptin liraglutide, patients insufficiently controlled on sitagliptin and metformin are more
likely to improve in glycaemic control, lose weight, and reduce their systolic blood pressure and hypoglycaemia.
T
his conclusion, based on
results of the randomised,
parallel-group, double-blind,
double-dummy, active-controlled
LIRA-SWITCH trial, was presented
at the meeting.
T. S. Bailey, MD, of the AMCR
Institute, Escondido, California,
explained that limited clinical
evidence is available to guide treat-
ment choices beyond the addition of
another drug to achieve glycaemic
target when second-line therapy is
inadequate for patients with type 2
diabetes.
The LIRA-SWITCH trial com-
pared the efficacy and safety of
switching from sitagliptin to lira-
glutide as an add-on to metformin
in subjects with type 2 diabetes
not achieving adequate glycaemic
control with sitagliptin + metformin.
Dr Bailey and colleagues com-
pared the proportion of subjects
meeting four composite endpoints
at 26 weeks, relating to glycaemia,
body weight, systolic blood pressure,
and hypoglycaemia outcomes.
Eligible subjects were at least
18 years of age, had haemoglobin
A 7.5–9.5% (58–80 mmol/mol),
body mass index
≥
20 kg/m
2
, had
been treated with stable doses of
sitagliptin (100 mg daily) and met-
formin (
≥
1500 mg daily or maximum
tolerated dose
≥
1000 mg daily) for
≥
90 days, and were randomised 1:1
to switch to liraglutide 1.8 mg or
continue sitagliptin 100 mg once
daily, both + metformin. Predefined
composite endpoints at week 26
were:
•
HaemoglobinA <7.0% (53 mmol/
mol) with no weight gain
•
Haemoglobin A <7.0%, with no
weight gain and systolic blood
pressure <140 mmHg
•
Haemoglobin A reduction
≥
1.0%
with no weighwt gain.
In addition, a post hoc analysis
of haemoglobin A<7.0%, with no
weight gain and no confirmed hypo-
glycaemic episodes was conducted.
A total of 407 subjects (male
60%, mean age 56 years, body mass
index 32 kg/m
2
, haemoglobinA 8.3%
[67 mmol/mol], type 2 diabetes dura-
tion 8 years) were randomised (lira-
glutide, n = 203; sitagliptin, n = 204).
At week 26, more subjects
achieved each of the
four composite end-
points by switching
from sitagliptin to liraglutide than
those who continued sitagliptin:
•
Haemoglobin A <7.0% with no
weight gain: 48.3% vs 24.2% (lira-
glutide and sitagliptin, respectively),
odds ratio 3.40, 95%CI 2.11; 5.49,
P < 0.0001
•
Haemoglobin A<7.0%, with no
weight gain and systolic blood
pressure <140 mmHg: 44.9% vs
19.2%, odds ratio 3.88, 95% CI
2.36; 6.39, P < 0.0001
•
Haemoglobin A reduction
≥
1.0%
with no weight gain: 52.8% vs
29.1%, odds ratio 2.85, 95% CI
1.82; 4.47, P < 0.0001
•
Haemoglobin A<7.0%, with no
weight gain and no confirmed hy-
poglycaemic episodes: 48.3% vs
24.2%, odds ratio 3.40, 95% CI
2.11; 5.49, P < 0.0001.
Dr Bailey concluded that switch-
ing from sitagliptin to liraglutide
resulted in more subjects achieving
each of the composite endpoints
analysed, than those who continued
sitagliptin. By switching from sitag-
liptin to liraglutide, patients insuf-
ficiently controlled on sitagliptin and
metformin are more likely to meet
clinically relevant goals relating to
glycaemia, body weight, systolic
blood pressure, and hypoglycaemia.
Outcomes that were more frequent in groups classified as having gestational diabetes by
either the WHO or NICE criteria.
•
WHO–Gestational Diabetes Mellitus, odds
ratio 1.56, 95% CI 1.03–2.38
•
NICE–Gestational Diabetes Mellitus 1.58,
95% CI 0.90–2.78
Induced delivery:
•
WHO–Gestational Diabetes Mellitus, odds
ratio 1.25, 95% CI 0.98–1.60
•
NICE–Gestational Diabetes Mellitus 1.54,
95% CI 1.11–2.13
Forceps or vacuum use:
•
WHO–Gestational Diabetes Mellitus, odds
ratio 1.29, 95% CI 1.01–1.64
•
NICE–Gestational Diabetes Mellitus 1.35,
95% CI 0.97–1.87
Acute caesarean section:
•
WHO–Gestational Diabetes Mellitus, odds
ratio 1.25, 95% CI 0.98–1.60
•
NICE–Gestational Diabetes Mellitus 1.54,
95% CI 1.11–2.13
Macrosomia >4000 g:
•
WHO–Gestational Diabetes Mellitus, odds
ratio 1.95, 95%CI 1.39–2.72
•
NICE–Gestational Diabetes Mellitus 1.16,
95% CI 0.67–2.00
Courtesy of EASD 2016
EASD 2016
VOL. 1 • No. 3 • 2016
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