DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
144
VOLUME 9 NUMBER 3 • SEPTEMBER 2012
Saxagliptin efficacy and safety in special patient groups
(
the elderly and those with renal impairment)
M
edications such as the DPP-4
inhibitors, which improve metabolic
control without increasing the risk of
hypoglycaemia, are important additions
to the treatment of older patients whose
susceptibility to hypoglycaemia increases
with age. Saxagliptin, a potent selective
DPP-4 inhibitor, has been shown to be
pharmacokinetically safe in patients over
the age of 65 years, compared to younger
healthy subjects.
1
In a pooled population of older patients
from five randomised, double-blind placebo
trials, saxagliptin 5 mg daily lowered HbA
1
c
levels from a baseline of 8.1% by –0.73 ±
0.16%
compared to patients on other oral
therapies who were not given saxagliptin.
2
While this study consisted of patients
mainly in the 65- to 75-year age group and
without impaired renal function or significant
cardiovascular disease, it is important
that HbA
1
c
and postprandial glucose levels
were safely and effectively lowered in
these patients without any weight gain.
The incidence of reported and confirmed
hypoglycaemia was very low and there were
no clinically meaningful interactions with
other anti-diabetic medications or agents
commonly used to treat hypertension or
hyperlipidaemia.
Renally impaired type 2 diabetes
patients
Kidney disease is common among type 2
diabetes patients, with approximately 20 to
30%
of patients developing renal damage
ranging from microalbuminuria to overt
nephropathy and ultimately renal disease.
In a double-blind placebo-controlled phase
III study with parallel groups, the efficacy and
safety of saxagliptinwas tested in patients with
moderate, severe or end-stage renal disease
(
ESRD) over a period of 12 weeks, with follow
up for a further 40 weeks (these results are not
yet available). In the first phase, the 12-week
study
3
patients were randomised to saxagliptin
2.5
mg once daily or placebo on top of their
normal diabetes therapy, which included oral
agents and insulin.
In the patients with moderate and severe
renal impairment, saxagliptin continued to
lower HbA
1
c
levels to targeted reductions.
In the ESRD subgroup, saxagliptin did not
lower HbA
1
c
levels more than placebo (those
treated with their standard anti-diabetic
therapy), likely because HbA
1
c
levels can be
falsely low in patients with ESRD because of
uraemia-induced changes in haemoglobin
structure.
Saxagliptin therapy in patients in
the moderate renal impairment group
(
creatinine clearance rate: CrCl ≥ 30 to
< 50 ml/min according to the Cockroft-
Gault equation) showed HbA
1
c
reductions
of (–0.64 vs –0.55%), whereas severely
impaired patients’ HbA
1
c
levels dropped
by 0.95 vs –0.50% in the placebo group.
Overall, saxagliptin was well tolerated with
a similar incidence of hypoglycaemia in
both treatment groups (20 vs 22.4% for
saxagliptin vs placebo).
While hypoglycaemia was more frequent
in renally impaired patients, the majority of
events were mild in intensity. Renal function
was not adversely affected during the
12-
week period in the saxagliptin-treated
group compared to the normal-therapy
(
placebo) group.
This study is important as it included type
2
diabetes patients with more advanced
disease and those with multiple concomitant
diseases, many of whom were on insulin.
J Aalbers
Boulton DW, Goyal A, li L,
1.
et al
.
The effects of age
and gender on the single-dose pharmacokinetics
and safety of saxagliptin in healthy subjects.
Diabetes Care
2008;
57
(
Suppl 1): Abstract 164.
Doucet J, Chacra A, Maheux P, Lu J, Harris S,
2.
Rosenstock J. Efficacy and safety of saxagliptin in
older patients with type 2 diabetes mellitus.
Curr
Med Res Opin
2011;
27
(4): 863–869.
