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168

VOLUME 11 NUMBER 4 • NOVEMBER 2014

LEARNING FROM PRACTICE

SA JOURNAL OF DIABETES & VASCULAR DISEASE

(53–110),

albumin:creatinine

ratio (ACR) 1.5 ± 2.4 mg/mmol (0.3–

7.5), cholesterol 4.4 ± 0.8 mmol/l (3.2–5.5), C-peptide was negative

{< 94 pmol/l [analysed by the Mercodia C-peptide enzyme-linked

immunosorbent assay (ELISA) assay]} in six patients and low in two

(281, 131 pmol/l), retinopathy status (none = 1, background = 2,

pre-proliferative and above = 5), foot risk (low risk = 5, intermediate

risk = 3) and only one patient had macrovascular complications.

On an intention-to-treat basis at three, six and 12 months,

weight loss was 6.8 ± 4.1 kg, 10.0 ± 5.6 kg and 9.0 ± 8.5 kg (range

–21 to +6.8 kg) (p = 0.026). Percentage weight loss at year end

was 8 ± 6% (range +4 to –16%). Daily insulin dose fell by 52 ± 69

units, 50 ± 69 units and 43 ± 60 units (median 16, range –168 to

+6 units) (

p

= 0.107, ns). Insulin dosage in units/kg was 1.0 ± 0.9,

0.7 ± 0.4, 0.7 ± 0.4 and 0.7 ± 0.6 (

p

= 0.136, ns). HbA

1c

changes

were not significant (

p

= 0.962, ns).

Two patients were unable to tolerate liraglutide and withdrew

at six months. They are indicated in Fig. 1. In one there was no

response in any parameter (HbA

1c

, weight or insulin dose), also

mandating withdrawal. In the other, weight and insulin dosage

rose following cessation of GLP-1 therapy. Excluding these two

cases (

n

= 6), insulin dose reduction over one year was significant

(

p

= 0.044) at 12 months (–44 ± 66 units per day) but with no

significant difference when assessed by units/kg (

p

= 0.158, ns).

Percentage weight loss at year end was 11 ± 3% (range –7 to

–16%,

p

= 0.003).

Alternatively, analysis to the six-month time point (

n

= 8) showed

significant falls in weight (

p

= 0.021) and a significant reduction in

insulin either by total daily dose (

p

= 0.045) or in daily units/kg (

p

=

0.044) while HbA

1c

remained static.

There were no significant hypoglycaemic events nor any episodes

of acute metabolic destabilisation.

Discussion

Under this tightly observed protocol, in motivated patients with

type 1 diabetes, under close clinical supervision (and by whatever

mechanisms of action

14-17

), significant weight reduction occurred

without metabolic destabilisation. Clinically and statistically signifi-

cant reductions in insulin dosages were achieved, which appeared

to be a consequence of the weight loss possibly indicative of an

improvement in insulin resistance as determined by the crude

Figure 1.

Percentage changes in weight (left panel) and total daily insulin dosage (right panel) over three, six and 12 months compared to baseline in individual cases.

Relevant individual baseline parameters are shown on the abscissa and are in ascending BMI order. Cases that withdrew at six months are denoted by an asterisk.

Table 1.

Mean ± SD (range) of outcomes of HbA

1c

, weight and insulin dosage over time in patients with type 1 diabetes treated with GLP-1 agonist

therapy; p-values are for the Friedman test for repeated measures over time. Significance is set at 0.05.

p

-value

6 months

12 months

Baseline

3 months

6 months

12 months

n

= 8

n

= 8

n

= 6

HbA

1c

(%)

8.5 ± 1.7

(7.1–12.5)

8.4 ± 1.3

(7.0–11.2)

8.0 ± 0.9

(6.7–8.7)

8.3 ± 1.6

(6.5–12.0)

0.497

0.771

0.409

Weight (kg)

123.0 ± 23.9

(70.9–153.2)

116.2 ± 24.5

(66.2–154.8)

113.0 ± 25.9

(62.0–155.0)

114.1 ± 26.4

(63.8–160.0)

0.021

0.026

0.003

Insulin dose

(units/day)

131 ± 112

(30–352)

79 ± 49

(30–166)

81 ± 49

(38–168)

89 ± 78

(28–270)

0.045

0.107

0.044

Insulin dose

(units/kg/day)

1.0 ± 0.9

(0.4–2.9)

0.7 ± 0.4

(0.4–1.5)

0.7 ± 0.4

(0.4–1.6)

0.8 ± 0.6

(0.4–2.3)

0.044

0.136

0.158