Shinshu Med J, 66⑸：319～324, 2018

Analysis for the Improvement of Inadequate Glycemic Control
in Patients with Type 2 Diabetes Mellitus in Nagano, Japan
Ai Sato1）†, Yoshihiko Sato1）＊†, Yuki Kobayashi1）
Masanori Yamazaki1）2） and Mitsuhisa Komatsu1）
1） Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine,
Shinshu University School of Medicine
2） Department of Drug Discovery Science, Shinshu University School of Medicine

Objectives and Methods : The present study was performed to determine whether patients with HbA1c ≥ 7.0 %can show improvement with additive treatments. A total of 252 patients ≤ 75 years old with type 2 diabetes
mellitus (T2DM) and with HbA1c ≥ 7.0 % were enrolled in this study. The primary endpoint was a rate ofachievement of HbA1c < 7.0 % in 1 year.
Results : HbA1c was ≥ 7.0 % (7.0 %-10.1 %) in all patients in the study population. Initially, mean HbA1c was
7.66 %±0.59 %. Thus, treatments were changed for 50.4 % of patients. However, treatment was not changed innearly half of the patients. In 3 months, mean HbA1c remained at 7.63 %±0.83 %, and HbA1c was < 7.0 % in
only 18.3 % of patients. At this time point, treatments were changed in 68.3 % of patients. Over 1 year, treat­ments were changed in a total of 86.5 % of the patients. However, only 27.8 % of patients had HbA1c < 7.0 %within 1 year.
Conclusion : The rate of reaching the target HbA1c in 1 year was only 27.8 % in our study population. This was
not sufficient for the control of blood glucose (BG). Thus, greater treatment intensity and further planning to im­prove patient condition are required to achieve the target. Shinshu Med J 66 : 319―324, 2018
(Received for publication March 29, 2018 ; accepted in revised form May 17, 2018)
Key words : type 2 diabetes mellitus, inadequate glycemic control, clinical inertia

Ⅰ Introduction
Diabetes is a disease with a worldwide distribu­

HbA1c level as < 7.0 %, which has been proven to beappropriate by many prospective studies performed
around the world1）-3）.

tion, which causes microvascular and macrovascular

Approaches to control BG in type 2 diabetes melli­complications. The aim of treatment of diabetic pa­tus (T2DM) include lifestyle improvements, such as

tients is to avoid these complications by controlling

diet and exercise. If these approaches are insufficient

blood glucose (BG) and to maintain the quality offor the control of BG, several medications, such as

patients’ lives. Hemoglobin A1c (HbA1c) is commonly

oral hypoglycemic agents (OHA) or injection of glu­

used as a marker of daily glycemic control. In 2013,cagon-like peptide-1 receptor agonists (GLP-1RA)

the Japan Diabetes Society (JDS) reported the target

or insulin, are selected as additional treatments.
However, more than half of all patients with T2DM＊

Corresponding author : Yoshihiko Sato
Division of Diabetes, Endocrinology and Metabolism,

Previously, we analyzed the level of BG control in

Department of Internal Medicine, Shinshu University

diabetic patients treated in clinics or hospitals in Na­

School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano
390-8621, Japan
E-mail : ysato@shinshu-u.ac.jp†

in Japan do not reach the target level of HbA1c4）.

Ai Sato and Yoshihiko Sato equally contributed to this study

No. 5, 2018

gano prefecture (presented at the annual meeting of
the JDS in 2013). In 2007, the mean HbA1c level ofall enrolled patients was 7.29 %. In Japan, the Diabe­319

A Sato・Y Sato・Kobayashi et al.
Table 1

Mean HbA1c levels of diabetic patients in 2007 and 2012 in Nagano, Japan
Year

n
Sex
Male
FemaleAge (years old)
Body mass index (kg/m2)
HbA1c (%)
Number of drugs for diabetes
Blood pressure
Systolic
Diastolic

2007

2012

P-value

3515

7418

1920 (55.2)
1558 (44.8)

4312 (58.4)
3069 (41.6)< 0.01

66.3 ± 12.3
24.3 ± 3.8
7.29 ± 1.18
1.49 ± 0.94

66.8 ± 12.4
24.9 ± 5.3
7.19 ± 1.20
1.68 ± 1.12

0.07
< 0.01< 0.01< 0.01132.8 ± 15.0
76.0 ± 10.6

132.9 ± 18.8
75.6 ± 10.7

0.84
0.10

Data are n (%) or mean ± SD.

tes Clinical Data Management Study Group (JDDM)

1 year. There were no special rules regarding how tobegan to collect annual data of mean HbA1c levels

improve glycemic control, except for no changes in4）of diabetic patients in 2000 , and our data were simi­
5）treatment within 3 months after an initial change. As

lar to those reported by the JDDM . In 2012, howev­

we did not obtain data about HbA1c in 1 year fromer, although new treatment methods, such as DPP4

18 patients, the data from 252 patients were included

inhibitors and GLP-1RA had become available inin the study.

6）
7）

2009 and 2010, respectively, the mean HbA1c level

had only decreased slightly to 7.19 % (Table 1).
In this study, we examined whether patients with
HbA1c ≥ 7.0 % can be improved with more stringent
treatment, e.g., the addition of new drugs and inten­sification of dietary control and exercise.
ⅡA

Materials and Methods

EthicsC

Statistical analysis
Values were compared using Welch’s t test, or χ2

test. In all analyses, P < 0.05 was taken to indicate
statistical significance.
Ⅲ

Results

The mean age, body mass index, and HbA1c level
were 60.0±10.3 years, 25.9±4.4 kg/m2, and 7.66 %±0.59 %, respectively, at the start of the study (TableThe study protocol was approved by the ethics2). HbA1c was ≥ 7.0 % in all patients (7.0 %-10.1 %).

committee of Shinshu University School of Medicine

Treatments were changed in 50.4 % of patients(Approved number 2273). All patients provided in­at the start of the study. Specifically, 69 patients

formed consent before participation.

(27.4 %) changed or added a new medication, and 2Bout of 69 patients changed their medication with

Inclusion criteria
A total of 270 consecutive T2DM patients ≤ 75

intensification of diet and/or exercise. 58 patients

years old (25-75 years old) with HbA1c ≥ 7.0 % (7.0-(23.0 %) intensified their diet and/or exercise without

10.1 %) from three clinics and six hospitals duringchanging medication. However, nearly half of the pa­

the period from 3 September 2013 to 13 February

tients did not change their treatments at this point2014 were included in the study. We collected clini­(Fig. 2, Table 2). In 3 months, mean HbA1c remained

cal data as shown in Fig. 1. The primary endpoint

at 7.63 %±0.83 %, and only 18.3 % of patients had

was a rate of achievement of HbA1c < 7.0 % in 1 year.

HbA1c < 7.0 %. Here, 31.3 % of patients changed or

Medical staff, including doctors of internal medicine,

added some treatments, so a total of 68.3 % changed

nurses, nutritionists, pharmacists, and exercise

their treatments during 0 and 3 months (Fig. 2). Sub­

trainers, tried to improve HbA1c to < 7.0 % withinsequently, 53.6 % of patients received a new treat­320

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Analysis for the improvement of inadequate glycemic control

270 patients with type 2 diabetes mellitus
Age ≤ 75 yo (25 – 75 yo)
HbA1c ≥ 7.0% (7.0 – 10.1%)
Diabetic complications
Retinopathy: None or Simple
Nephropathy: 1st or 2nd stage
1. Backgroundage, sex, height, weight,
duration of outpatient treatment
2. HbA1c
3. Presence/absence of diabetic retinopathy, nephropathy
4. Blood pressure
5. Treatment (diet/exercise and OHA, GLP-1RA, Insulin)
18 patients were
excluded

252 patients

Table 2

Fig. 1 Enrollment of patients.
A total of 270 diabetic patients were initiallyenrolled in the study. They were ≤ 75 years
old and had HbA1c ≥ 7.0 %. We collectedclinical data as outlined above. Finally, 252patients were included in the study.

Background of patients and initial changes of treatment at 0 months

n
Sex
Male
FemaleAge (years old)
Body mass index (kg/m2)

252
149 (59.1)
103 (40.9)
60.0 ± 10.3
25.9 ± 4.4
7.66 ± 0.59
2 (0.8)67 (26.6)
58 (23.0)
125 (49.6)

HbA1c (%)

Changes of treatment on enrollment

Medication ＋ Diet/Exercise
Medication only
Diet/Exercise only
No change of treatment

Data are n (%) or mean ± SD.

ment approach during the period from 3 to 12 months

initial HbA1c < 8.0 % showed better improvement; therefore, the treatment approach was changed inthan those with HbA1c ≥ 8.0 %. None of the patientsa total of 86.5 % of cases over the period of 12 months

with initial HbA1c ≥ 9.0 % reached HbA1c < 7.0 %(Fig. 2). However, mean HbA1c was 7.59 %±0.96 %,within 1 year (Table 4).

and only 27.8 % of patients had HbA1c < 7.0 % within
1 year (Fig. 2, Table 3). Changes in both medication

Ⅳ

Discussion

and diet/exercise showed a better tendency on the rate

Despite the development of several new treat­of HbA1c improvement compared with no change ofments for T2DM, nearly half of the patients did nottreatment, although there was no statistical signif­show sufficient daily BG control5）. The reasons may

icance (Table 3).

vary, e.g., problems in daily life, such as overeating

Finally, we evaluated the relationship between ini­or lack of exercise, or medications may not be suffi­tial HbA1c level and the rate of achievement of HbA1cciently efficacious in some patients. In daily medical< 7.0 % within 1 year. As expected, patients withtreatment, it is necessary to identify the specificNo. 5, 2018321

A Sato・Y Sato・Kobayashi et al.

Medication only
No change

100%
100
90%

8

86.5%

7.9

80%

7.8

70%

7.7

68.3%

60%
50
50%

7.6
7.5

50.4%

40%

7.4

30%

7.3

20%

7.2

10%
0%0

7.1

Mean HbA1c (%)

Rate of treatment change (%)

Medication + Diet/Exercise
Diet/Exercise only
HbA1c

7
0

3

6

9

12

MonthsHbA1c < 7.0%
(%)

0

18.3

27.8

Fig. 2 Rates of treatment change and mean HbA1c at 0, 3, and 12 months.
The total rate of change in medication and diet/exercise for improvement of BG increased gradually.
The mean HbA1c was 7.66 % ± 0.59 %, 7.63 % ± 0.83 %, and 7.51 % ± 0.96 % at 0, 3, and 12 months, respectively.
Table 3

 elationship between change of treatment and rate of patients who achieved
R
HbA1c < 7.0 % in 1 year
No. of patients

Patients with
HbA1c < 7.0 %P-value

All patients
Medication + Diet/Exercise

252
42 (16.7)

70 (27.8)
14 (33.3)

0.22

Medication only
Diet/Exercise only
No change of treatment

151 (60.0)
25 (9.9)34 (13.5)

42 (27.8)
7 (28.0)
7 (20.6)

0.39
0.50
-

Changes of treatment

Data are n (%). P-values are for comparison with no change of treatment.
Table 4 Relationship between initial HbA1c level and rate of patients who achieved
HbA1c < 7.0 % in 1 year
HbA1c (%) on enrollmentnChange in HbA1c(%)

Achievement in
1 yearP-value

7.0 - 7.9
8.0 - 8.9≥ 9.0

190 (75.4)
51 (20.2)
11 (4.4)

－0.08
－0.39
－0.04

62 (32.6)
8 (15.7)
0 (0.0)< 0.05< 0.05

Data are n (%). P-values are for comparisons of 7.0 % - 7.9 % to 8.0 % - 8.9 %, ≥ 9.0 %, respectively.

problems for each patient. However, this is some­Seven types of OHA, GLP-1RA, and insulin aretimes difficult because of a lack of information re­currently available for the treatment of T2DM.

garding the daily lives of patients.

Many diabetic patients do not adhere to ideal diet322

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Analysis for the improvement of inadequate glycemic control

control or exercise in their daily lives, and thereforeＶthere are many approaches to improve BG.

Conclusions

In this study, we could have changed or intensified

The rate of reaching the target HbA1c < 7.0 % inglycemic management because all patients had

1 year was only 27.8 %. This rate was disappoint­

HbA1c ≥ 7.0 %. However, 13.5 % of patients did noting, and insufficient for the control of daily BG. To

receive new treatments during the test period de­achieve the target, more intensive treatments andspite the availability of multiple tools for glycemic

more precise analysis of problems specific for eachcontrol.

patient are required. Then, we should plan how to

In daily outpatient clinics, clinicians tend to be
slow to intensify glycemic control. This is so-called

improve the patients’ condition and empower thepatients themselves to control their disease.

clinical inertia, defined as “recognizing the problem

Acknowledgments

but failing to act”8）-10）. Strain et al. suggested that
impairment of communication lies at the heart ofWe thank all of the researchers who participatedclinical inertia9）. This is often the case in daily treat­in this study as follows : Dr. Hisae Ota and Dr. Yasu­

ment of diabetes, and clinicians should not compro­

haru Ota (Ota DM Clinic), Dr. Yasuyuki Karasawa

mise the treatment for improvement of glycemic(Karasawa Internal Medicine), Dr. Atsushi Momose

control.

(Koujindo Clinic), Dr. Yuji Aoki (Matsumoto Hospi­

In 2014, we obtained further unique tools for thetal), Dr. Tomoko Tanaka (Tanaka Hospital), Dr. Masuo

treatment of T2DM, i.e., sodium-glucose co-transporter

Tokoo (Azumino Red Cross Hospital), Dr. Koji Naka­

2 inhibitor (SGLT2i). The major feature of this drug

jima and Dr. Tomohiro Niwa (Iida Municipal Hospi­

is excretion of a certain amount of glucose in thetal), Dr. Takanari Miyahara and Dr. Fukue Ishizu

11）
12）

urine

, which enables decreases in not only BG but(Nagano Matsushiro General Hospital).

also body weight of patients. Thus, we can expect

Disclosuresabout 0.8 %-1.0 % reduction of HbA1c and 2-3 kg ofbody weight with SGLT2i. When this study began

Mitsuhisa Komatsu has received honoraria for lec­

in 2013, SGLT2is were not in clinical use in Japan.

tures from Novo Nordisk Pharma Ltd., Takeda Phar­

These drugs became available in April 2014, so many

maceutical Co., Ltd., Eli Lilly Japan K. K., MSD K. K.,

clinicians seldom prescribed SGLT2is during theSumitomo Dainippon Co., Ltd., Mitsubishi Tanabe

study period. Therefore, further studies are required

Pharma Co., and donations from Takeda Pharmaceu­

to re-estimate the improvement of HbA1c with thesetical Co., Ltd., Novartis Pharma K. K.

drugs.

The other authors have no potential conflicts ofinterest associated with this research.
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