diabetes research and clinical practice 108 (2015) e67e70

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Diabetes Research
and Clinical Practice
journ al h ome pa ge : www .elsevier.co m/lo cate/diabres

Brief Report

Saxagliptin is similar in glycaemic variability more

effective in metabolic control than acarbose in aged
type 2 diabetes inadequately controlled with
metformin
Man-man Wang a,1, Shuo Lin a,1, Yan-ming Chen a, Jiong Shu a,
Hong-yun Lu b, Yong-jun Zhang c, Ru-ying Xie a, Long-yi Zeng a,
Pan-wei Mu a,*
a

Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
Department of Endocrinology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
c
Department of Endocrinology, The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519100, China
b

article info

abstract

Article history:

This study compared the effects on glycaemic variability and glucose control between

Received 21 October 2014

saxagliptin and acarbose as add-on therapies for aged T2DM inadequately controlled with

Received in revised form

metformin alone. The results showed that compared with acarbosemetformin, saxaglip-

26 January 2015

tinmetformin was more effective in glucose control with similar glycaemic variability.

Accepted 19 February 2015

# 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under

Available online 13 March 2015

the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords:
Saxagliptin
Acarbose
Glycaemic variability
Type 2 diabetes mellitus

1.

Introduction

Glycaemic variability (GV) is an HbA1c-independent risk factor

in the development of diabetic complications [1]. It should be

considered along with HbA1c in the management of diabetes

[2]. As an add-on drug, acarbose is known to improve GV [3,4].
Saxagliptin is a new anti-diabetic drug, whose effect on GV is
still unclear. Therefore we compared the GV and glucose
control between saxagliptin and acarbose as add-on therapies

* Corresponding author. Tel.: +86 20 85253408; fax: +86 20 85252160.

E-mail address: [email protected] (P.-w. Mu).
1
These authors contributed equally to this paper.
Abbreviations: GV, glycaemic variability; HbA1c, glycosylated hemoglobin; T2DM, type 2 diabetes mellitus; FBG, fasting blood glucose;
SMBG, self-monitoring of blood glucose; IDF, International Diabetes Federation; SDBG, standard deviation of blood glucose; LAGE, largest
amplitude of glycaemic excursions; DPP-4, dipeptidylpeptidase-4.
http://dx.doi.org/10.1016/j.diabres.2015.02.022
0168-8227/# 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

e68

diabetes research and clinical practice 108 (2015) e67e70

for aged type 2 diabetes mellitus (T2DM) inadequately

controlled with metformin alone.

2.

Research design and methods

Ninety outpatients aged over 60 years, with FBG >8.5 mmol/L

and HbA1c >7.5% (58 mmol/mol) while treated metformin
alone for more than six months, were enrolled. Patients were
excluded if they had acute complications or other disorders
affecting glucose metabolism. The protocol and informed
consent document were approved by the Research Ethics
Board of the Third Affiliated Hospital of Sun Yat-Sen
University.
After enrollment, patients were randomized to saxagliptin
5 mg once daily or acarbose 50 mg three times daily for
one year. Seven-point finger blood glucoses (fasting, 2 h after
breakfast, pre-lunch, 2 h after lunch, pre-dinner, 2 h after
dinner, and pre-bedtime) were measured by self-monitoring
of blood glucose (SMBG) on three consecutive days at
randomization, the 3rd month, the 6th month, and the end
of the study. At the same time physical examinations and
laboratory tests were undertaken.
Non-normally distributed variables were log-transformed
first. Paired t-test was performed to examine differences

between baseline and post-intervention. For the assessment

of differences between two groups, t-test was performed. Chisquare test was used to analyze the differences of incidence of
hypoglycaemia and rates of HbA1c <7.0% (53 mmol/mol)
between two groups.

3.

Results and discussion

Of the ninety patients randomized, eighty-one (90.0%) patients

(forty-one in saxagliptin and forty in acarbose) completed the
study (supplementary data 1). Two groups were similar at
randomization for all variables. After adding saxagliptin or
acarbose, weight, hepatic and renal function did not change.
Insulin resistance (HOMA-IR), b-cell function (HOMA-b), and
lipid metabolism seemed to ameliorate but without significance. These improvements were more obvious in saxagliptin than in acarbose but of no significance (supplementary
data 2). During the study, there were no severe hypoglycaemic
episodes-an event requiring another persons assistance. The
proportion of patients with minor hypoglycaemia-defined as
having finger blood glucose level below 3.9 mmol/L and
prompt recovery after self-administered carbohydrate-was
higher in saxagliptin (4.88%, 2 of 41) than in acarbose (0.00%, 0
of 40) (P > 0.05).

Fig. 1 Comparison of HbA1c and FBG between saxagliptin and acarbose.

diabetes research and clinical practice 108 (2015) e67e70

HbA1c and FBG decreased markedly in both groups. This

reduction was more noticeably in saxagliptin than in acarbose
(P < 0.05) (Fig. 1). More patients reached HbA1c <7.0%
(53 mmol/mol), which is recommended by IDF [5], in saxagliptin (7.32%, 3 of 41) than in acarbose (2.50%, 1 of 40)
(P > 0.05) (supplementary data 1). Standard deviation of blood
glucose (SDBG) and largest amplitude of glycaemic excursions
(LAGE) decreased significantly with similar end point levels in
both groups (P > 0.05). Adding saxagliptin or acarbose, both
blood glucose curves flatted. The curves of two combinations
were similar in fluctuation at each designated corresponding
time, respectively (Fig. 2).
GV is another sign of dysglycaemia. Clinical studies reveal
GV is a significant predictor of mortality in T2DM [6,7]. In
cellular consequences, intermittent high glucose stimulates a
more reactive oxygen species overproduction, a greater
adhesion molecules overexpression, and an extra cell apoptosis than constant high glucose [810]. As a result, GV is
regarded as an important risk factor in the development of
diabetic complications. Our results confirmed previously
published papers reporting that acarbose reduced GV
[3,4,11]. Saxagliptin is a dipeptidylpeptidase-4 (DPP-4) inhibitor, which increases glucose-dependent insulin secretion and
suppresses glucagon secretion [12]. Consequently it mainly
targets postprandial hyperglycaemia. As a result, saxagliptin
decreases GV effectively just like acarbose. The present study

e69

suggested that saxagliptin was more effective in lowering

HbA1c and FBG than acarbose. This may lie in its insulinstimulated property. Studies indicate that insulin secretagogues reduce overall glycaemia and FBG superior to acarbose
[3,13]. Other reports show DPP-4 inhibitors are non-inferior to
insulin secretagogues [14,15]. Furthermore, DDP-4 inhibitors
have various effects on b-cell: stimulating b-cell production;
inhibiting b-cell apoptosis and restoring islet cell mass
[12,16,17]. Moreover, DDP-4 inhibitors have effects on the
gastrointestinal tract: promoting satiety, suppressing food
intake and delaying gastric emptying. All of these may
contribute to saxagliptins more effective in reducing HbA1c
and FBG. Other studies report DPP-4 inhibitors and aglucosidase inhibitors have similar glucose-lowering effect
[18,19]. This discrepancy may be attributed to the different
subjects as well as different background treatments. For
example, it is reported DPP-4 inhibitors are more efficacious in
the Asians [20].
This study had some limitations. First a 7-point glycaemic
feature could not comprehensively represent the glycaemic
profile of a whole day. Furthermore we did not use the test
meal. The patients glucose levels could be influenced.
However, we collected data on three consecutive days but
not on one day, which could lessen the influence. In addition,
the data of daily life instead of load test could rather
successfully reflect real world in clinical practice. Finally

Fig. 2 Comparison of SDBG, LAGE, and blood glucose curve between saxagliptin and acarbose.

e70

diabetes research and clinical practice 108 (2015) e67e70

the study indicated some results between saxagliptin and

acarbose, but gave little insight as to the mechanism. Further
studies are required to validate the present results and
investigate the mechanism.

[7]

4.

[8]

Conclusions

In aged T2DM inadequately controlled with metformin alone,

saxagliptinmetformin has similar effect on glucose excursion
with acarbosemetformin, and the former has a stronger
effect on glucose control than the latter.

[9]

Conflict of interest
The authors declare that they have no conflict of interest.

[10]

Acknowledgements
[11]

This study was funded by the Guangdong Pharmaceutical

Association (2012C04). We thank all of the doctors, nurses,
technicians, and patients involved for their dedication to the
study.

[12]

Appendix A. Supplementary data

[13]

Supplementary data associated with this article can be

found, in the online version, at http://dx.doi.org/10.1016/j.
diabres.2015.02.022.

[14]

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