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VOLUME 11 NUMBER 4 • NOVEMBER 2014
167
SA JOURNAL OF DIABETES & VASCULAR DISEASE
LEARNING FROM PRACTICE
The use of liraglutide, a GLP-1 agonist, in obese people
with type 1 diabetes
SYED MR GILLANI, BALDEV M SINGH
Correspondence to: Dr Syed MR Gillani
Wolverhampton Diabetes Centre, New Cross Hospital, Wednesfield Road,
Wolverhampton, UK
Tel: +44 (0)1902 695313
e-mail:
syed.gillani@nhs.netBaldev M Singh
Wolverhampton Diabetes Centre, New Cross Hospital, Wolverhampton, UK.
Previously published in
Br J Diabetes Vasc Dis
2014;
14
: 98–101
S Afr J Diabetes Vasc Dis
2014;
11
: 167–169
Abstract
Aim:
Optimisation of glycaemic control in type 1 diabetes often
results in unwanted weight gain. Glucagon-like peptide-1
(GLP-1) agonist use is associated with weight reduction in
type 2 diabetes but its use in type 1 diabetes is little studied.
Methods:
We developed a protocol for GLP-1 use in people
with type 1 diabetes and obesity in which liraglutide was
initiated and up-titrated while insulin doses were simul-
taneously titrated according to glycaemic parameters.
Results:
Of 15 patients offered treatment, eight proceeded.
Baseline parameters were (
n
= 8, mean ± SD): (age 50 ± 6
years, BMI 40.4 ± 5.5 kg/m
2
, weight 123.0 ± 23.9 kg, HbA
1c
8.5 ±
1.7%, total daily insulin dose 131 ± 112 units/day. By intention
to treat analysis (
n
= 8, 12 months), at three, six and 12 months
compared to baseline, weight loss was 6.8 ± 4.1 kg, 10.0 ± 5.6
kg and 8.9 ± 8.4 kg, respectively (
p
= 0.026). The reductions
in insulin dosage were significant over six months (
n
= 8,
p
= 0.045) or when analysing only those who completed 12
months of liraglutide therapy (
n
= 6,
p
= 0.044).
Conclusions:
GLP-1 agonist use in patientswith type 1 diabetes
may be advantageous where weight reduction becomes both
a constraint and a therapeutic objective.
Keywords:
GLP-1, insulin, liraglutide, obese, type 1 diabetes, weight
Introduction
The management of type 1 diabetes is complex with multiple
challenges. Optimisation of glycaemic control plays a key role in
the prevention of both macro- and microvascular complications
1
but often results in unwanted weight gain
2
and adverse clinical
outcomes.
3
Even small reductions in weight significantly improve
outcomes of obesity-related chronic diseases.
4
Currently lifestyle
modifications are the mainstay of treatment of obesity in type 1
diabetes. While pharmacotherapy can augment the effect of life
style modifications,
5
its role is limited such that bariatric surgery is
often the only effective treatment for morbid obesity.
6
One of its
subsidiary mechanisms may be increased production of glucagon
like peptide-1 (GLP-1)
7
since GLP-1 regulates appetite and satiety.
That may be one reason, among many, why GLP-1 agonist use is
associated with significant weight reduction in type 2 diabetes
8
and
the non-diabetic obese population.
9,10
GLP-1 agonist use in type 1
diabetes is little studied either for the modification of glycaemic
control or for weight. Preliminary evidence suggests liraglutide use
in type 1 diabetes benefits glycaemic control, glucose variability,
reduced dosage of insulin and body weight.
11-13
Based on this,
we have developed and audited a local protocol for the use of
liraglutide in obese patients with type 1 diabetes.
Methods
We developed a protocol for GLP-1 use in people with type 1
diabetes, obesity [body mass index (BMI) > 35 kg/m
2
], progressive
weight gain with or without constraint to insulin titration for better
glycaemic control. The diagnosis of type 1 diabetes was according to
standard clinical and biochemical parameters (acute onset, ketosis
at presentation, insulin therapy from diagnosis and mandatory on-
going insulin need, C-peptide levels). Acceptance of patients onto
the protocol required dual consultant–specialist approval. After
providing them with relevant information at consultation and in
writing using a standardised information sheet, informed written
agreement was obtained from all patients about the dual unlicensed
use of liraglutide in type 1 diabetes and for the management of
obesity. Liraglutide was initiated and up-titrated from 0.6 to 1.8 mg
over a four- to six-week period, while insulin doses were titrated
according to glycaemic parameters. Patients had open access to
support and follow up, and were minimally reviewed monthly. The
key objectives were safe glycaemic control, weight loss of > 5% at
six months and GLP-1 agonist tolerability.
Patients were reviewed for withdrawal at three months and
withdrawn at six months if these were not attained. This protocol
was agreed with local clinical governance committees, but since
this was a service development and the presented data are an audit
of the protocol, formal ethical committee approval was deemed
not to be required. Statistical analysis was in SPSS version 21.
The non-parametric Freidman test for repeated, related measures
was applied to test differences in parameters over time with
p
< 0.05 taken as significant. Data are presented as the mean ± SD
with the range.
Results
Over one year, of 15 patients offered treatment, seven declined and
eight proceeded (age 50 ± 6 years, four females). One patient with
BMI 30 kg/m
2
was included due to rapid weight rise during insulin
intensification, such that the patient did not want to proceed
without co-management of weight gain.
Summary results are presented in Table 1 and individual out-
comes are shown in Fig. 1.
The baseline parameters were: BMI 40.4 ± 5.5 kg/m
2
, (range
30–47.7 kg/m
2
), weight 123.1 ± 23.9 kg (70.9–153.2 kg), glycated
haemoglobin (HbA
1c
) 8.5 ± 1.7% (7.1–12.5%), total daily insulin dose
131 ± 112 units/day (30–352 units/day), creatinine 76 ± 21 µmol/l