Received: 29 January 2019 Revised: 17 March 2019 Accepted: 28 March 2019

DOI: 10.1111/dom.13733

BRIEF REPORT

Determining the optimal fasting glucose target for patients

with type 2 diabetes: Results of the multicentre, open-label,
randomized-controlled FPG GOAL trial

Wenying Yang MD1 | Jianhua Ma MD2 | Guoyue Yuan MD3 | Ling Li MD4 |
Min Zhang MD5 | Yibing Lu MD6 | Xinhua Ye MD7 | Weihong Song MD8 |
Ming Liu MD9 | Jun Wu MD10 | Riqiu Chen MD11 | Yunguang Li MD12 |
Xia Zhang MD12 | Nan Cui MD12 | Jinkui Yang MD13

1
Endocrine Department, China-Japan
Friendship Hospital, Beijing, China Abstract
2
Endocrine Department, Nanjing First Hospital, The optimal fasting blood glucose (FBG) target of achieving HbA1c less than 7.0% in type
Nanjing Medical University, Nanjing, China
2 diabetes (T2D) patients remains controversial. This open-label trial randomized (1:3:3)
3
Endocrine Department, Affiliated Hospital of
Jiangsu University, Zhenjiang, China 947 adults with uncontrolled T2D (HbA1c >7% to ≤10.5%) who were using one to three
4
Endocrine Department, Shengjing Hospital of oral antidiabetic drugs to achieve an FBG target of 3.9 < FBG ≤5.6 mmol/L (Group 1),
China Medical University, Shenyang, China
3.9 < FBG ≤6.1 mmol/L (Group 2) or of 3.9 < FBG ≤7.0 mmol/L (Group 3). Targets were
5
Endocrine Department, Qingpu Branch of
Zhongshan Hospital, Affiliated with Fudan
achieved using a pre-defined insulin glargine 100 U/mL titration scheme. The primary
University, Shanghai, China endpoint was proportion of patients achieving HbA1c <7.0% at 24 weeks. At 24 weeks,
6
Endocrine Department, The Second Affiliated 44.4%, 46.1% and 37.7% of patients achieved HbA1c <7.0% in Groups 1, 2 and 3, respec-
Hospital, Nanjing Medical University, Nanjing, China
7 tively (P = 0.017; Group 2 vs Group 3). Alert hypoglycaemia (glucose ≤3.9 mmol/L) was
Endocrine Department, Changzhou Second
People's Hospital, Affiliated with Nanjing significantly more frequent in Group 1 than in Group 3 (38.9 vs 23.3%; P < 0.001) but
Medical University, Changzhou, China
was not in Group 2 vs Group 3 (27.5% vs 23.3%; P = 0.177). Clinically important
8
Endocrine Department, Chenzhou
No. 1 People's Hospital, Chenzhou, China hypoglycaemia (glucose ≤3.0 mmol/L) was reported in 4.8%, 2.0% and 3.8% of patients
9
Endocrine Department, Tianjin Medical in Groups 1, 2 and 3, respectively. In conclusion, the optimal FBG target for most Chi-
University General Hospital, Tianjin, China
nese patients with T2D appears to be 3.9-6.1 mmol/L.
10
Endocrine Department, The Third Hospital
of Wuhan, Wuhan, China
KEYWORDS
11
Endocrine Department, Lishui People's
fasting blood glucose, glycated haemoglobin, insulin glargine, type 2 diabetes
Hospital, Lishui, China
12
Medical Department, Sanofi Investment Co.,
Ltd., Shanghai, China
13
Endocrine Department, Beijing Tongren
Hospital, Beijing, China

Correspondence
Wenying Yang MD, Endocrine Department,
China-Japan Friendship Hospital, East
Yinghuayuan Street, Hepingli, Beijing 100029,
People's Republic of China.
Email: [email protected]

Funding information
This study was supported by Sanofi.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Diabetes Obes Metab. 2019;21:1973–1977. wileyonlinelibrary.com/journal/dom 1973

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1974 YANG ET AL.

Peer Review
The peer review history for this article is
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10.1111/dom.13733.

1 | I N T RO D UC T I O N on Harmonisation guidelines for good clinical practice. An institutional

review board at each site approved the study, and all participants gave
Most current guidelines for management of type 2 diabetes (T2D) rec- written informed consent.
ommend that patients maintain glycated haemoglobin (HbA1c) levels
below 7% to achieve long-term glucose control.1-5 While a goal of
2.2 | Procedures
HbA1c <7.0% is given in guidelines as suitable for the majority of
patients with T2D,1-5 the corresponding fasting blood glucose (FBG) At randomization, all study patients initiated subcutaneous once-daily
target to achieve this goal is not clearly defined. Guidelines from the insulin glargine 100 U/mL (Lantus SoloSTAR, Sanofi-Aventis Deutschland
American Diabetes Association (ADA) in 2018 recommend an FBG tar- GmbH, Frankfurt, Germany) at a dose of 0.2 U/kg. During the study,
get of 4.4-7.2 mmol/L to achieve HbA1c <7%.1 Guidelines from the patients measured FBG daily, using a blood glucose meter, and study phy-
American Association of Clinical Endocrinologists-American College of sicians reviewed the self-monitored FBG values and titrated the basal
Endocrinology in 2018 and from the International Diabetes Federation insulin dose at each study visit (Table S1). The lowest value of the last
in 2017 recommend an FBG target of <6.1 mmol/L to achieve HbA1c three consecutive self-monitored FBG values was used for decisions con-
3 4 cerning insulin titration at each visit.
<6.5% and < 7%, respectively. Thus, the optimal FBG target to
achieve HbA1c <7.0% in patients with T2D remains controversial. Patients continued to receive baseline OADs for the duration of
Only one study, conducted in a Western country, demonstrated the study; these could be decreased or discontinued only at the inves-
that more patients randomized to an FBG target of 3.9-5.0 mmol/L tigators' discretion based on safety and in accordance with Chinese
achieved HbA1c <7.0% than those randomized to an FBG target of treatment guidelines and local label indications.
6
4.4-6.1 mmol/L. However, the proportion of patients who achieved
HbA1c <7% without hypoglycaemia (glucose ≤3.1 mmol/L) was the
2.3 | Endpoints and assessments
same in the two target groups.6 The present study was designed to
evaluate the effect of three pre-defined FBG targets on the propor- The primary endpoint was the proportion of patients achieving HbA1c
tion of Chinese patients with T2D who achieved HbA1c <7.0%.7 The <7% at 24 weeks. Secondary endpoints included the proportion of
FBG targets to which patients were randomized were 3.9 < FBG ≤7.0, patients achieving HbA1c <7% without hypoglycaemia (blood glucose
3.9 < FBG ≤6.1 and 3.9 < FBG ≤5.6 mmol/L. Titration with basal insu- ≤3.9 [alert] or ≤ 3.0 mmol/L [clinically important]) at 24 weeks, change
lin glargine 100 U/mL was chosen to provide FBG control. In sum- from baseline in HbA1c, FBG, postprandial glucose and FPG at
mary, this study aimed to elucidate the optimal FBG target for 24 weeks, distribution of patients with FPG or FBG ≤5.6 mmol/L,
patients with T2D to maximize the proportion of patients to achieve 5.6-6.1 mmol/L, 6.1-7.0 mmol/L and > 7.0 mmol/L at Week 24, final
HbA1c <7% while minimizing hypoglycaemia risk. insulin dose in each arm at the end of the study, frequency and inci-
dence of hypoglycaemia (definitions provided in Table S2) and changes
in body weight. Exploratory endpoints included the proportion of
2 | MATERIALS AND METHODS
patients with HbA1c <7% according to groups re-divided by actual
24-week FPG levels, and the relationship between mean FBG over one
2.1 | Participants
to 12 weeks and HbA1c at 12 weeks and between mean FBG over
This was a 24 week, open-label, parallel-group, randomized, treat-to- 13 to 24 weeks and HbA1c at 24 weeks. Additional safety outcomes
target study (ClinicalTrials.gov identifier: NCT02545842). The study included frequency and severity of adverse events (AEs) were coded
7
design and methods have been reported previously. Briefly, eligible using MedDRA version 18.1. Sample size calculation and methods of
patients were between 18 and 65 years of age, had a diagnosis of T2D, statistical analysis are provided online in Supporting Information.
with HbA1c >7% to ≤10.5% despite stable doses of one to three oral
anti-hyperglycaemic drugs (OADs) for at least 3 months, had fasting
3 | RESULTS
plasma glucose (FPG) of >7 mmol/L, had a body mass index of ≥20 to
≤40 kg/m2, had a duration of diabetes of at least 1 year, and were willing
3.1 | Participants
to initiate treatment with basal insulin. Patients were randomly assigned
(1:3:3) to one of three FBG target groups: 3.9 < FBG ≤ 5.6 mmol/L Between 7 September 2015 and 20 April 2018, 947 patients from
(Group 1), 3.9 < FBG ≤ 6.1 mmol/L (Group 2) or 3.9 < FBG ≤ 7.0 mmol/L 44 sites in China were randomly assigned to Group 1 (n = 136), Group
(Group 3). Randomization was stratified by use of sulfonylurea. 2 (n = 405) or Group 3 (n = 06). Of these, 885 patients completed the
The study was conducted in accordance with the principles of the study. The most common reasons for study discontinuation were
Declaration of Helsinki and in line with the International Conference patient withdrawal and protocol violations (Figure S1). Demographic
 14631326, 2019, 8, Downloaded from https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.13733 by EBMG ACCESS - COTE D'IVOIRE, Wiley Online Library on [01/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
YANG ET AL. 1975

TABLE 1 Baseline characteristics in the full analysis set

FBG target > 3.9 mmol/L to

Characteristic ≤5.6 mmol/L (n = 126) ≤6.1 mmol/L (n = 393) ≤7.0 mmol/L (n = 395) Total (n = 914) P valuea
Age, y 54.1 ± 7.2 54.2 ± 7.4 53.5 ± 7.4 53.9 ± 7.4 0.392b
Male, n (%) 69 (54.8) 214 (54.5) 231 (58.5) 514 (56.2) 0.490c
Disease duration, y 8.2 ± 5.5 8.0 ± 4.7 7.8 ± 4.8 7.9 ± 4.8 0.707b
HbA1c, % 8.50 ± 0.91 8.63 ± 0.92 8.57 ± 0.94 8.59 ± 0.92 0.314b
HbA1c, mmol/mol 69 ± 9.9 71 ± 10.1 70 ± 10.3 70 ± 10.1 0.314b
Serum FPG, mmol/L 10.4 ± 2.2 10.6 ± 2.2 10.5 ± 2.3 10.5 ± 2.3 0.636b
Self-monitored FBG, mmol/L 9.3 ± 1.9 9.6 ± 2.0 9.5 ± 2.0 9.5 ± 2.0 0.287b
PPG, mmol/L 13.2 ± 3.8 13.8 ± 3.7 13.9 ± 3.7 13.8 ± 3.7 0.226b
Insulin dose, U/d 12.2 ± 2.5 12.7 ± 2.7 12.6 ± 2.8 12.6 ± 2.7 0.284b
Insulin dose, U/kg.d 0.18 ± 0.03 0.18 ± 0.03 0.18 ± 0.03 0.18 ± 0.03 0.417b
Weight, kg 69.6 ± 11.6 70.5 ± 11.7 70.1 ± 11.2 70.2 ± 11.4 0.757b
BMI, kg/m2 25.5 ± 3.0 25.6 ± 3.0 25.6 ± 3.2 25.6 ± 3.1 0.936b
Sulphonylurea use, n (%) 82 (65.1) 243 (61.8) 244 (61.8) 569 (62.3) 0.780c
Glimepiride 46 (36.5) 114 (29.0) 121 (30.6) 281 (30.7)
Gliclazide 21 (16.7) 92 (23.4) 86 (21.8) 199 (21.7)
Other 15 (11.9) 37 (9.4) 37 (9.4) 89 (9.7)
Number of OADs, n (%) 0.408d
1 18 (14.3) 65 (16.6) 52 (13.2) 135 (14.8)
2 84 (66.7) 253 (64.7) 251 (63.5) 588 (64.5)
3 24 (19.0) 73 (18.7) 92 (23.3) 189 (20.7)

Note: Values are presented as mean ± standard deviation unless otherwise stated.
Abbreviations: BMI, body mass index; FBG, fasting blood glucose; FPG, fasting plasma glucose; OADs, oral anti-hyperglycaemic drugs; PPG, postprandial
glucose.
a
Global nominal p-values assessing differences between the three FBG target groups.
b
ANOVA.
c
Fisher's Exact Test.
d
Chi-Squared Test.

and baseline characteristics were similar across groups (Table 1). 3.2.2 | Secondary endpoints
Patients had a mean age of 53.9 years (56.2% male) and a mean dura-
No difference was observed among groups in the proportion of
tion of diabetes of 7.9 years. The majority of patients were receiving
patients who achieved HbA1c <7% without alert hypoglycaemia
two OADs at baseline (64.5%) and 62.3% were receiving treatment
(≤3.9 mmol/L) (Figure 1). In contrast, a significantly greater proportion
with sulphonylureas.
of patients in Group 2 achieved HbA1c <7%, without clinically impor-
tant hypoglycaemia (≤3.0 mmol/L), than in Group 3 (45.0% vs 36.5%
of patients; P = 0.014) (Figure 1).
3.2 | Efficacy All patients experienced mean reductions from baseline in
glycaemic parameters (Table S3). However, patients in Groups 1 and
3.2.1 | Primary endpoint
2 experienced significantly greater reductions from baseline in HbA1c,
At 24 weeks, 44.4%, 46.1% and 37.7% of patients had an HbA1c level FBG and FPG at 24 weeks as compared to patients in Group
less than 7% in Groups 1, 2 and 3, respectively (Figure 1). The propor- 3 (Table S3).
tion of patients achieving HbA1c <7% was numerically, but not signifi- After 24 weeks, 70.1%, 67.6% and 79.0% of patients in Groups
cantly, higher in Group 1 vs Group 3 (P = 0.183); thus, the second 1, 2 and 3, respectively, had FBG values within their pre-defined
fixed-sequence hypothesis test was not performed. E xploratory target range according to a pre-planned titration strategy based
Bonferroni-adjusted (α < 0.025) analysis showed a significant differ- on lowest value of the last three consecutive FBG values. Detailed
ence in the proportion of patients achieving HbA1c <7% in Group distribution of FBG and FPG in each group is described in
2 vs Group 3 (P = 0.017). Table S4.
 14631326, 2019, 8, Downloaded from https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.13733 by EBMG ACCESS - COTE D'IVOIRE, Wiley Online Library on [01/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1976 YANG ET AL.

Target 3.9<FBG≤5.6 mmol/L (n=126) 4 | DISCUSSION

Target 3.9<FBG≤6.1 mmol/L (n=393)
60 Target 3.9<FBG≤7.0 mmol/L (n=395)
44.4 a 43.7 b To our knowledge, this is the first prospective randomized study to exam-
Proportion of patients (%) + 95% CI

46.1 45.0
50 ine the effect of three FBG targets on HbA1c control among patients
37.7
36.5 with T2D, affording the opportunity to identify an optimal FBG target
40 29.4 32.8
associated with a balanced efficacy and safety profile. The results showed
27.8
30 that the proportion of patients who achieved HbA1c <7% or HbA1c <7%
without clinically important hypoglycaemia (≤3.0 mmol/L) was signifi-
20 cantly higher in the 3.9 < FBG ≤6.1 mmol/L target group than in the
3.9 < FBG ≤7.0 mmol/L target group (46.1% vs 37.7% or 45.0% vs
10
36.5%). The frequency or incidence rate of hypoglycaemia did not differ
0 significantly between patients randomized to the 3.9 < FBG ≤6.1 mmol/L
HbA1c <7% HbA1c <7% w/o HbA1c <7% w/o
target and those randomized to the 3.9 < FBG ≤7.0 mmol/L target, with
hypo (≤3.9 mmol/L) hypo (≤3.0 mmol/L)
Glycaemic target at 24 weeks the exception of the incidence rate of the “any hypoglycaemia” category.
Taken together, these findings suggest that a 3.9 < FBG ≤6.1 mmol/L tar-
F I G U R E 1 Achievement of HbA1c < 7% and HbA1c < 7%
get represents the optimal balance between glycaemic control and safety.
without hypoglycaemia at 24 weeks by FBG target group (n = 914,
LOCF, FAS). Abbreviations: FAS, full analysis set; FBG, fasting blood One previously published study evaluated the effect of two differ-
glucose; hypo, hypoglycaemia; LOCF, last observation carried ent FBG targets (3.9-5.0 mmol/L or 4.4-6.1 mmol/L) on HbA1c con-
forward; w/o, without. aP < 0.025 for Bonferroni-adjusted analysis; trol; however, it had some limitations.6 Although more patients
*nominal P < 0.05 vs FBG ≤7.0 mmol/L achieved HbA1c <7.0% with the lower FBG target (64.3% vs 54.5%;
P = 0.04), the proportion of patients achieving HbA1c <7.0% without
The doses of insulin administered at 24 weeks to patients in
hypoglycaemia (≤3.0 mmol/L) was the same (44.6% vs 44.6%;
Groups 1 and 2 were significantly greater (P < 0.001) than the dose
P = 0.796).6 The study examined only two FBG targets, both weighted
administered to patients in Group 3 (Table S3).
towards the lower end of the FBG spectrum, limiting its ability to
reveal an FBG target with an optimal efficacy and safety profile com-
3.2.3 | Exploratory endpoints pared with a higher FBG target, such as the 7.0 mmol/L target rec-
ommended by the ADA and by Chinese guidelines.1,5 In contrast, our
The proportion of patients with HbA1c less than 7%, according to
study, which employed three FBG targets, was better able to identify
groups re-divided by actual 24-week FPG levels, and the relationship
a 3.9 < FBG ≤6.1 mmol/L target as representative of the optimal bal-
between mean FBG and HbA1c are described online.
ance between efficacy and safety for the majority patients with T2D.
This study has limitations. While the 3.9 < FBG ≤5.6 mmol/L tar-
get group experienced a significantly larger reduction in HbA1c at
3.3 | Safety
24 weeks, as compared with the 3.9 < FBG ≤7.0 mmol/L target group,
Overall, 65% of patients experienced an AE during the 24-week treat- there was no significant difference in the proportion of patients who
ment period, the majority of which were mild in severity. The most achieved HbA1c <7% between these target groups. This is possibly
common AEs were hypoglycaemia, upper respiratory tract infections, explained by the fact that our sample size calculations assumed a dif-
nasopharyngitis and toothache (Table S5). Less than 2% of the study ference of 15% in achieving HbA1c <7% between the
population discontinued the study because of an AE and no deaths 3.9 < FBG≤5.6 mmol/L and 3.9 < FBG≤7.0 mmol/L target groups.8
occurred during the treatment period. However, the actual between-group difference was approximately7%;
Alert hypoglycaemia (≤3.9 mmol/L) was significantly more frequent thus, the study was underpowered to detect these differences.
in Group 1 than in Group 3 (38.9 vs 23.3%; P < 0.001) but was not sig- In conclusion, our study showed a balanced efficacy and safety
nificantly more frequent in Group 2 than in Group 3 (27.5% vs 23.3%; profile among patients with an FBG target of 3.9 to 6.1 mmol/L,
P = 0.177). Similar findings were seen concerning any hypoglycaemia, suggesting that this could be an optimal target for the majority of
symptomatic hypoglycaemia and nocturnal hypoglycaemia. However, patients with T2D.
there were no significant differences in clinically important
hypoglycaemia (≤3.0 mmol/L) among the three groups (4.8%, 2.0% and
3.8%, respectively; all P ≥ 0.05). Severe hypoglycaemia occurred in only
ACKNOWLEDG MENTS
one patient each in Groups 2 and 3 (Table S5). The incidence rate of
hypoglycaemia was similar to the frequency of hypoglycaemia, with the We thank the patients, the investigators (see Appendix S1 for a full list
exception of the “any hypoglycaemia” category (Table S5). of study investigators) and their staff for participating in the study.
Although body weight increased by 0.5-0.7 kg in all target FBG We would also like to thank Simone Tait and Julian Martins of
groups, no significant between-group differences in change from inScience Communications, Springer Healthcare, who provided pro-
baseline in body weight were observed (Table S5). fessional medical writing assistance which was was funded by Sanofi.
 14631326, 2019, 8, Downloaded from https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.13733 by EBMG ACCESS - COTE D'IVOIRE, Wiley Online Library on [01/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
YANG ET AL. 1977

CONF LICT OF IN TE RE ST 2. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglyce-
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board participation from Sanofi Aventis, Novo Nordisk, AstraZeneca, of diabetes (EASD). Diabetes Care. 2018;41:2669-2701.
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the American Association of clinical endocrinologists and American
and Servier; and has also received investigator-initiated trial
College of endocrinology on the comprehensive type 2 diabetes man-
research grants from AstraZeneca, outside of the submitted work. agement algorithm - 2018 executive summary. Endocr Pract. 2018;24:
L. L. has received honoraria for speakers' bureau participation from 91-120.
Sanofi Aventis, Novo Nordisk, Bayer, Takeda, Eli Lily, Merck and 4. International Diabetes Federation. Recommendations for managing
type 2 diabetes in primary care. 2017. www.idf.org/managing-type2-
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diabetes. Accessed September 21, 2018.
raria for speakers' bureau participation from Sanofi Aventis and 5. Weng J, Ji L, Jia W, et al. On behalf of Chinese Diabetes Society Standards
Novo Nordisk, outside of the submitted work. X. Y. has received of care for type 2 diabetes in China. Diabetes Metab Res Rev. 2016;32:
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6. Blonde L, Merilainen M, Karwe V, Raskin P. Patient-directed titration
Merck Sharp & Dohme and Novo Nordisk, outside of the submitted
for achieving glycaemic goals using a once-daily basal insulin analogue:
work. J. M., G. Y., M. Z., Y. L., W. S., M. L., J. W., J. Y. have no con- an assessment of two different fasting plasma glucose targets - the
flict of interests to disclose. Y. L., X. Z. and N. C. are employees of TITRATE study. Diabetes Obes Metab. 2009;11:623-631.
Sanofi China. 7. Yang W, Yang Z, Zhao J, Lu H, Luo T. Assessment of three fasting
plasma glucose targets for insulin glargine-based therapy in people
with type 2 diabetes mellitus in China: study protocol for a randomized
AUTHOR CONTRIBUTIONS controlled trial. Trials. 2016;17:470.
8. Pan C, Tian H, Li Q, et al. Potential value of the Asian treat to target
The study was designed by W. Y. W. Y., J. M., G. Y., L. L., M. Z., Y. L., Lantus study (ATLAS) for type 2 diabetes management in China: safety
and efficacy of two treatment algorithms using insulin glargine. Chin J
X. Y., W. S., M. L., J. W., R. C. and J. Y. were in charge of individual
Endocrinol Metab. 2015;31:865-871.
study centres; they recruited patients and conducted the study. Y. L.,
X. Z. and N. C. participated in study design and coordinated study
centres. All authors contributed to the writing of the report. W. Y. is SUPPORTING INF ORMATION
the guarantor of this article.
Additional supporting information may be found online in the
Supporting Information section at the end of this article.
ORCID

Wenying Yang https://orcid.org/0000-0002-7997-9404 How to cite this article: Yang W, Ma J, Yuan G, et al.
Determining the optimal fasting glucose target for patients
with type 2 diabetes: Results of the multicentre, open-label,
RE FE R ENC E S
randomized-controlled FPG GOAL trial. Diabetes Obes Metab.
1. American Diabetes Association. 6. Glycemic targets: standards of med- 2019;21:1973–1977. https://doi.org/10.1111/dom.13733
ical care in Diabetes-2018. Diabetes Care. 2018;41:S55-S64.