Page 49 - The SA Journal Diabetes & Vascular Disease Volume 9 No 4 (November 2012)

VOLUME 9 NUMBER 4 • NOVEMBER 2012 191
SA JOURNAL OF DIABETES & VASCULAR DISEASE REPORT
ing the elderly and those with diabetic
nephropathy. 1-4 The phase 3 study evalu-
ated the long-term safety and efficacy of
the addition of linagliptin versus placebo in
1 261 patients inadequately controlled on
basal insulin therapy.
The overall safety and tolerability of
linagliptin was comparable to placebo. The
incidence of hypoglycaemia was also com-
parable in both groups (linagliptin 31.4%,
placebo 32.9%), despite better glycaemic
control with linagliptin (–0.53% place-
bo-adjusted change in HbA1c level from
baseline at week 52, p < 0.0001). (HbA1c
level is measured in people with diabetes
to provide an index of blood glucose con-
trol for the previous two to three months.)
Body weight was stable over the treatment
period in both groups.1
Linagliptin as add-on to basal insulin
therapy has also shown safety and efficacy
in elderly patients (older than 70 years) in
a separate pre-specified pooled analysis of
two phase 3 studies evaluating linagliptin
versus placebo as add-on therapy to basal
insulin over 24 weeks and as T2D manage-
ment in elderly patients.
Elderly patients with T2D are commonly
characterised by longer disease duration
and diminished beta-cell capacity, which
often require combination therapy with
basal insulin. In this vulnerable elderly
population, linagliptin in combination with
basal insulin was well tolerated, with the
overall incidence of adverse events (AE) not
higher than that with placebo.
Linagliptin achieved improvements in gly-
caemic control of –0.77% (placebo-adjusted
change in HbA1c level from baseline, p <
0.0001), without excessive risk of hypogly-
caemia. Hypoglycaemia occurred in 28.6%
on linagliptin and 37.2% on placebo.4
A third analysis of seven phase 3 trials
assessed a variety of safety and efficacy
parameters associated with linagliptin
use as monotherapy or add on to various
glucose-lowering therapies in elderly T2D
patients (older than 65 years). Results from
this analysis showed that linagliptin was
well tolerated and might be a treatment
option for elderly patients without the
need for dose adjustment.
Linagliptin showed a reduction in glucose
levels as measured by a –0.62% (p < 0.0001)
placebo-adjusted change in HbA1 c level from
baseline to week 24. Patients treated with
linagliptin also experienced a significantly
greater reduction in fasting plasma glucose
(FPG) (placebo-adjusted mean change of
–14.8 mg/dl; –0.82 mmol/l, p < 0.0001)
and the number of AEs was not higher than
those on placebo (71.3 vs 73.3%). Drug-re-
lated AEs were also not higher with linaglip-
tin compared to placebo (18.1 vs 19.8%).3
‘This is very encouraging data in this
often challenging-to-trea t patient popula-
tion’, said Prof Anthony Barnett, Emer itus
Professor of Medicine, University of Birming-
ham, UK. ‘Many elderly patients have addi-
tional safety and tolerability concerns, such
as co-morbidities, compromised renal func-
tion and heightened risk of hypoglycaemia.
Linagliptin appears to be an effective and
well-tolerated treatment option for type 2
diabetes in the elderly without the n eed for
dose adjustment or extra monitoring, even
if kidney function declines. In a situation
where treatment choices are more and more
limited, linagliptin is a welcome addition to
our therapeutic armamentarium .’
In a separate analysis, linagliptin showed
efficacy in another vulnerable T2D patient
population – those with diabetic nephropa-
thy. Many patients with T2D have diabetic
nephropathy shortly after diagnosis, and
may go on to develop end-stage kidney
disease. Currently, there are only very lim-
ited oral treatment options available for
T2D patients with renal disease.
An analysis of seven randomised trials was
performed and data after 24 weeks of treat-
ment were generated to allow pooling and
two sets were defined: (1) diabetic nephrop-
athy in earlier stages of T2D patients with
persistent albuminuria [30 ≤ UACR (urine
albumin-to-creatine ratio) ≤ 3 000 mg/g]
and stable treatment with an ACE inhibitor
( angiotensin converting enzyme inhibitor)
or ARB (angiotensin II receptor blocker); (2)
diabetic nephropathy in elderly patients (65
years) who fulfilled the UACR criteria .
Patients from set 1 were treated with or
without oral glucose-lowering background
therapies. Patients from set 2 had various
glucose lowering background therapies,
including insulin therapy.
Patients in set 1 experienced placebo-
corrected changes in HbA1c level and a fast-
ing plasma glucose level of –0.71% and
–1.4 mmol, respectively (both p < 0.0001).
Linagliptin also significantly lowered UACR
by 33% ( p < 0.05). In set 2, linagliptin sig-
nificantly lowered adjusted UACR by 30%
( p < 0.05). The reduction of albuminuria
was beyond what may be expected by the
glucose -lowering effects of linagliptin in
both sets.2
1. Yki-Järvinen H, Rosenstock J, Durán-Garcia S, et
al. Long-term safety and efficacy of linagliptin as
add-on therapy to basal insulin in patients with
type 2 diabetes: a 52-week randomised, placebo-
controlled trial. Oral presentation no 6 presented
at the 48th European Association for the Study of
Diabetes (EASD) annual meeting, Berlin, Germany,
1–5 October 2012.
2. Groop P, Cooper M, Perkovic V, et al. Effects of the
DPP-4 inhibitor linagliptin on albuminuria in patients
with type 2 diabetes and diabetic nephropathy.
Abstract at the 48th European Association for the
Study of Diabetes (EASD) annual meeting, Berlin,
Germany, 1–5 October 2012.
3. Patel S, Schernthaner G, Barnett A, et al. Safety
and efficacy of linagliptin in elderly patients with
type 2 diabetes: evidence from 1 331 individuals
aged ≥ 65 years. Presented at the 48th European
Association for the Study of Diabetes (EASD) annual
meeting Berlin, Germany, 1–5 October 2012.
4. Woerle HJ, Neubacher D, Patel S, et al. Safety and
efficacy of linagliptin plus basal insulin combination
therapy in a vulnerable population of elderly
patients (age = 70 years) with type 2 diabetes.
Presented at the 48th European Association for
the Study of Diabetes (EASD) annual meeting,
Berlin, Germany, 1–5 October 2012.
Tighter regulation of medical
devices in diabetes care
The European Union is set to tighten regula-
tion of medical devices, following concerns
expressed by the EASD concerning quality
management of devices in diabetes care,
such as glucose monitors and pumps. The
proposals call for a wider scope of devices
requiring regulation and more power to reg-
ulate products, such as unannounced factory
inspections and more frequent sampling.
Increased leisure-time physical
activity reduces cardiovascular risk
after diagnosis of type 2 diabetes
While it is not surprising that type 2 dia-
betes patients who exercise regularly sig-
nificantly reduce their risk of cardiovascular
events, analyses from the Swedish National
Diabetes Register (NDR) found that diabet-
ics who did little or no exercise at baseline,
but who then succeeded in increasing their
leisure-time physical activity levels over
approximately five years, slashed their risk
of death by almost two-thirds.
In this review of more than 15 000 indi-
viduals with type 2 diabetes, patients were
grouped as either low (no regular exercise)
or regular exercise. Those with regular exer-
cise had fewer cardiovascular events. For
those who moved from no regular exercise
to exercising at least three times per week
by the end of the 4.8-year study period, the
number of cardiovascular deaths decreased
by 67%. Rates of all-cause mortality were