VOLUME 10 NUMBER 3 • SEPTEMBER 2013
85
SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
co-morbidities, such as renal impairment, which may increase their
susceptibility to hypoglycaemia.
6
The higher risk of hypoglycaemia
associated with sulphonylureas (when compared with non-insulin
therapies) may limit their overall clinical utility in this group. They do
however offer a cheaper treatment per unit price. DPP-4 inhibitors
have some characteristics which may be of particular value in older
patients. They can be taken orally, as opposed to insulin or GLP-1
analogues, and they are comparatively well tolerated. Indeed, the
most recent ADA-EASD position statement specifically lists their
advantage as rarely having severe side effects as opposed to the
other treatment options.
7
We set out to study the DPP-4 inhibitor
class in the clinical practice setting due to the paucity of data for
this class and population.
Aim
The aim of the study was to examine the efficacy and tolerability of
DPP-4 inhibitors in older patients with type 2 diabetes mellitus whilst
focusing on particular pertinent aspects relevant to care of older
persons. Patients who had received treatment with DPP-4 inhibitors
were compared with a control group of patients with type 2 diabetes
mellitus who had never been treated with DPP-4 inhibitors.
Methods
Patients with a diagnosis of type 2 diabetes mellitus over 60 years
of age were randomly selected from primary and secondary care
settings in England (in the counties of Warwickshire, Hertfordshire,
Bedfordshire, Cambridgeshire, Suffolk and Greater London). This
included nine separate GP practices and three NHS Trust Hospitals.
This study was approved as an audit by the regional ethics
committee. The investigators liaised with the relevant Caldicott
guardians in primary care and the audit departments of hospitals
to gain authorised access to the data. Encrypted data storage
devices were used to protect data during data transfer and analysis
of results. Data were collected by reviewing the electronic medical
records, clinical hospital notes and laboratory results. For blood
results to be included in the study, the patient had to have received
three months’ continuous treatment with the medication before
the test was performed. Statistical analysis was performed using
Microsoft Excel (Microsoft, Reading, UK) and SPSS software (IBM,
Middlesex, UK).
Categorical variables were described using number and
percentage and analysed for significance using Pearson’s chi-
squared (
χ
2
) test. Continuous variables were described using
medians and ranges, and were analysed for significance using the
Mann-Whitney U test (two tailed), for non-parametric variables.
Chronic kidney disease was defined as an eGFR < 60 ml/min
as calculated according to the MDRD equation.
8
Hypoglycaemia
was recorded when this was documented in the clinical patient
records.
Mild hypoglycaemia was defined as hypoglycaemia documented
in the medical records which did not require additional support.
Severe hypoglycaemia was defined as when subjects required
assistance to recover (e.g. ambulance call-out, hospitalisation,
supporter/relative assistance to aid recovery).
Results
The analysed data-set included 431 randomly selected patients
with 129 patients in the DPP-4 group and 302 in the control
group (i.e. never treated with DPP-4 inhibitors). Demographic and
cardiovascular risk factor data are shown in Table 1. The median
age (range) for the DPP-4 inhibitors group was 70 (60–92) years
compared with 77 years (60–95) years (
p
< 0.001). All other
parameters did not differ significantly.
Statistically significant diabetic complication rates in DPP-4
inhibitors vs. control were 14% vs. 31% for neuropathy (
p
< 0.001);
20 vs 33% for chronic kidney disease (
p
= 0.004).
The respective treatments (shown in Table 2) in the DPP-4
inhibitors and control groups were diet control only 0 vs 24%;
metformin 88 vs. 47% (
p
< 0.001); sulphonylurea 53 vs 25%
(
p
< 0.001); insulin 7 vs 30% (
p
< 0.001); and for pioglitazone
17 vs 6% (
p
< 0.001).
No severe hypoglycaemic events were recorded (i.e. there was no
specific mention of these events in the clinical notes as defined). Mild
hypoglycaemia in DPP-4 inhibitors versus control (defined as health
care professional documented hypoglycaemia in the patient clinical
records) was 3 vs 8% (
p
= 0.062) and no patients required admission
in the last year as a consequence of hypoglycaemia. The incidence
of hypoglycaemia and risk factors for developing hypoglycaemia
are shown in Table 3. In the DPP-4 inhibitors group the 4 out of
Table 1.
Demographic and cardiovascular factor risk data.
DPP-4 treated
group (
n
= 129)
Control group
(
n
= 302)
p-
value for
comparison
Age (median, range)
70 (60–92)
77 (60–95)
< 0.001
Male
82 (64%)
165 (54%)
NS
Treated primary care 104 (81%)
243 (81%)
NA
Body mass index
(kg/m
2
)
29
30
NS
Smoking status:
NS
• Current
• Ex-smokers
• Never
9 (7%)
58 (45%)
146 (48%)
15 (5%)
67 (48%)
141 (47%)
Blood pressure
(mmHg)
130/72
131/75
NS
Total cholesterol
(mmol/l)
3.8
3.8
NS
LDL-cholesterol
(mmol/l)
2.0
1.8
NS
HbA
1C
(%) (median,
range)
7.4 (5.7–10.3)
7.2 (5.1–12.6)
NS
Duration diabetes
(years)
8
8
NS
CKD (eGFR < 60 ml/
min)
25 (20%)
100 (33%)
0.004
Microalbuminuria
11 (9%)
27 (9%)
NS
Retinopathy
36 (28%)
61 (20%)
NS
Neuropathy
18 (14%)
95 (31%)
< 0.001
Ischaemic heart
disease
28 (21%)
88 (29%)
NS
Stroke
10 (8%)
33 (10%)
NS
Peripheral arterial
disease
5 (4%)
23 (8%)
NS
CKD: chronic kidney disease; DPP: dipeptidylpeptidase; eGFR: estimated
glomerular filtration rate; HbA
1c
: glycated haemoglobin; LDL: low-density
lipoprotein cholesterol; NA: not applicable; NS: not significant,
p
values
>0.05.
