J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website https://www.jofem.org

Original Article

Volume 11, Number 1, February 2021, pages 8-13

Comparison of Metformin and Alogliptin Fixed-Dose Tablets Once a Morning Versus Once an Evening Using Continuous Glucose Monitoring (AMPM Study): An Open-Label Randomized Cross-Over Trial

Figure 2. Correlation of HDL-C levels with drug response. HDL-C: high-density lipoprotein cholesterol; L/HBGI: low/high blood glucose indices.

**Table 1.** Baseline Demographics and Laboratory Data of Patients With T2D
Variables	Mean (SD)
T2D: type 2 diabetes; BMI: body mass index; HbA1c: hemoglobin A1c; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; HLS: healthy lifestyle score; SD: standard deviation.
Age, years	57.2 (11.2)
BMI, kg/m²	26.1 (4.6)
HbA1c, %	8.2 (1.5)
TC, mg/dL	204 (26)
HDL-C, mg/dL	52 (11)
TG, mg/dL	166 (97)
Chronotype, %
Morning type	36.4
Intermediate	45.5
Evening type	18.2
HLS, points (out of 8)	3.8 (1.7)

Table 1. Baseline Demographics and Laboratory Data of Patients With T2D

Variables

Mean (SD)

T2D: type 2 diabetes; BMI: body mass index; HbA1c: hemoglobin A1c; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; HLS: healthy lifestyle score; SD: standard deviation.

Age, years

57.2 (11.2)

BMI, kg/m²

26.1 (4.6)

HbA1c, %

8.2 (1.5)

TC, mg/dL

204 (26)

HDL-C, mg/dL

52 (11)

TG, mg/dL

166 (97)

Chronotype, %

Morning type

36.4

Intermediate

45.5

Evening type

18.2

HLS, points (out of 8)

3.8 (1.7)

**Table 2.** Comparison of AM or PM Administration of Drug
Variables	AM group	PM group	P value
HbA1c: hemoglobin A1c; GA: glycated albumin; 1, 5-AG: 1, 5-anhydroglucitol; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; TC: total cholesterol; TG: triglycerides; TP: total protein; Alb: albumin; BUN: blood urea nitrogen; SCr: serum creatinine; UA: urinalysis; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: γ-glutamyl transferase; hs-CRP: high-sensitivity C-reactive protein.
HbA1c, %	7.9 (1.3)	-0.2 (0.4)	8.0 (1.4)	-0.5 (0.7)	0.307
GA, %	19.9 (4.8)	0.1 (3.9)	21.9 (5.6)	-2.1 (3.0)	0.145
1, 5-AG, %	7.5 (7.5)	1.0 (1.9)	9.3 (7.9)	-0.6 (3.9)	0.224
TC, mg/dL	205 (39)	-7 (19)	198 (35)	3 (15)	0.219
HDL-C, mg/dL	54 (10)	2 (5)	54 (12)	2 (5)	0.851
TG, mg/dL	148 (78)	-33 (74)	145 (82)	-8 (87)	0.466
TP, mg/dL	7.3 (0.4)	0.1 (0.3)	7.4 (0.3)	-0.1 (0.3)	0.395
Alb, mg/dL	4.3 (0.2)	0.0 (0.1)	4.3 (0.2)	0.1 (0.2)	0.789
BUN, mg/dL	25.7 (28.8)	-7.9 (30.3)	16.2 (3.3)	1.3 (3.2)	0.317
SCr, mg/dL	0.7 (0.1)	0.0 (0.0)	0.7 (0.2)	-0.0 (0.1)	0.303
UA, mg/dL	5.1 (1.1)	0.1 (1.0)	5.1 (1.4)	0.1 (0.5)	0.960
AST, IU/L	27 (13)	2 (11)	24 (12)	3 (5)	0.794
ALT, IU/L	34 (29)	1 (14)	31 (27)	1 (4)	0.955
GGT, IU/L	37 (28)	0 (6)	38 (22)	1 (7)	0.726
hs-CRP, mg/dL	0.15 (0.22)	0.04 (0.41)	0.12 (0.09)	-0.02 (0.14)	0.652

Table 2. Comparison of AM or PM Administration of Drug

Variables

AM group

PM group

P value

Baseline

Changes

Baseline

Changes

HbA1c: hemoglobin A1c; GA: glycated albumin; 1, 5-AG: 1, 5-anhydroglucitol; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; TC: total cholesterol; TG: triglycerides; TP: total protein; Alb: albumin; BUN: blood urea nitrogen; SCr: serum creatinine; UA: urinalysis; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: γ-glutamyl transferase; hs-CRP: high-sensitivity C-reactive protein.

HbA1c, %

7.9 (1.3)

-0.2 (0.4)

8.0 (1.4)

-0.5 (0.7)

0.307

GA, %

19.9 (4.8)

0.1 (3.9)

21.9 (5.6)

-2.1 (3.0)

0.145

1, 5-AG, %

7.5 (7.5)

1.0 (1.9)

9.3 (7.9)

-0.6 (3.9)

0.224

TC, mg/dL

205 (39)

-7 (19)

198 (35)

3 (15)

0.219

HDL-C, mg/dL

54 (10)

2 (5)

54 (12)

2 (5)

0.851

TG, mg/dL

148 (78)

-33 (74)

145 (82)

-8 (87)

0.466

TP, mg/dL

7.3 (0.4)

0.1 (0.3)

7.4 (0.3)

-0.1 (0.3)

0.395

Alb, mg/dL

4.3 (0.2)

0.0 (0.1)

4.3 (0.2)

0.1 (0.2)

0.789

BUN, mg/dL

25.7 (28.8)

-7.9 (30.3)

16.2 (3.3)

1.3 (3.2)

0.317

SCr, mg/dL

0.7 (0.1)

0.0 (0.0)

0.7 (0.2)

-0.0 (0.1)

0.303

UA, mg/dL

5.1 (1.1)

0.1 (1.0)

5.1 (1.4)

0.1 (0.5)

0.960

AST, IU/L

27 (13)

2 (11)

24 (12)

3 (5)

0.794

ALT, IU/L

34 (29)

1 (14)

31 (27)

1 (4)

0.955

GGT, IU/L

37 (28)

0 (6)

38 (22)

1 (7)

0.726

hs-CRP, mg/dL

0.15 (0.22)

0.04 (0.41)

0.12 (0.09)

-0.02 (0.14)

0.652

**Table 3.** Comparison of Glucose Parameters Between Treatment Time (AM vs. PM)
Variables	Treatment time	Difference	P value
AUC: area under curve; L/HBGI: low/high blood glucose indices.
Mean	165.7 (48.1)	160.0 (44.1)	-5.6 (19.0)	0.778
Standard deviation	43.5 (13.2)	43.6 (10.3)	0.0 (7.2)	0.992
Glucose time, %
< 54	0.3 (0.9)	0.1 (0.2)	-0.2 (0.8)	0.533
54 - 70	0.3 (0.8)	0.2 (0.4)	-0.1 (0.8)	0.773
70 - 180	66.1 (27.8)	70.6 (25.2)	4.5 (14.1)	0.696
> 180	33.3 (28.0)	29.1 (25.3)	-4.2 (14.3)	0.714
AUC, mg·h/dL
Total	528,705 (674,078)	351,419 (584,807)	-177,285 (395,354)	0.517
0:00 - 6:00	18,820 (40,621)	15,126 (42,961)	-3,694 (6,850)	0.838
6:00 - 12:00	27,829 (40,755)	23,687 (43,604)	-4,142 (16,392)	0.820
12:00 - 18:00	32,132 (40,347)	28,699 (37,962)	-3,433 (29,372)	0.839
18:00 - 24:00	37,391 (47,698)	23,593 (36,091)	-13,798 (27,844)	0.453
HBGI	7.8 (8.8)	7.0 (7.9)	-0.8 (3.1)	0.817
LBGI	0.3 (0.4)	0.3 (0.2)	0.0 (0.4)	0.946

Table 3. Comparison of Glucose Parameters Between Treatment Time (AM vs. PM)

Variables

Treatment time

Difference

P value

AM group

PM group

AUC: area under curve; L/HBGI: low/high blood glucose indices.

Mean

165.7 (48.1)

160.0 (44.1)

-5.6 (19.0)

0.778

Standard deviation

43.5 (13.2)

43.6 (10.3)

0.0 (7.2)

0.992

Glucose time, %

< 54

0.3 (0.9)

0.1 (0.2)

-0.2 (0.8)

0.533

54 - 70

0.3 (0.8)

0.2 (0.4)

-0.1 (0.8)

0.773

70 - 180

66.1 (27.8)

70.6 (25.2)

4.5 (14.1)

0.696

> 180

33.3 (28.0)

29.1 (25.3)

-4.2 (14.3)

0.714

AUC, mg·h/dL

Total

528,705 (674,078)

351,419 (584,807)

-177,285 (395,354)

0.517

0:00 - 6:00

18,820 (40,621)

15,126 (42,961)

-3,694 (6,850)

0.838

6:00 - 12:00

27,829 (40,755)

23,687 (43,604)

-4,142 (16,392)

0.820

12:00 - 18:00

32,132 (40,347)

28,699 (37,962)

-3,433 (29,372)

0.839

18:00 - 24:00

37,391 (47,698)

23,593 (36,091)

-13,798 (27,844)

0.453

HBGI

7.8 (8.8)

7.0 (7.9)

-0.8 (3.1)

0.817

LBGI

0.3 (0.4)

0.3 (0.2)

0.0 (0.4)

0.946

**Table 4.** Correlation of Clinical Parameters With HBGI and LBGI
Variables	HBGI	LBGI
BMI: body mass index; HLS: healthy lifestyle score; HbA1c: hemoglobin A1c; GA: glycated albumin; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; L/HBGI: low/high blood glucose indices.
Age	-0.284	-0.449	-0.347	0.309	0.121	-0.222
BMI	0.180	0.388	0.489	-0.117	0.126	0.180
Male	0.253	0.243	-0.099	0.105	-0.454	-0.351
Evening type in chronotype	-0.499	-0.325	0.592	0.206	0.322	-0.013
HLS	-0.180	-0.405	-0.532	-0.163	0.241	0.287
HbA1c	-0.054	-0.007	0.137	-0.189	0.081	0.222
GA	0.163	0.078	-0.268	0.036	0.108	0.027
TC	0.063	0.019	-0.133	-0.298	-0.265	0.130
HDL-C	0.261	0.055	-0.608 *	0.161	0.003	-0.149
TG	-0.095	-0.072	0.088	-0.439	-0.136	0.334

Table 4. Correlation of Clinical Parameters With HBGI and LBGI

Variables

HBGI

LBGI

AM group

PM group

Difference (PM - AM)

AM group

PM group

Difference (PM - AM)

BMI: body mass index; HLS: healthy lifestyle score; HbA1c: hemoglobin A1c; GA: glycated albumin; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; L/HBGI: low/high blood glucose indices.

Age

-0.284

-0.449

-0.347

0.309

0.121

-0.222

BMI

0.180

0.388

0.489

-0.117

0.126

0.180

Male

0.253

0.243

-0.099

0.105

-0.454

-0.351

Evening type in chronotype

-0.499

-0.325

0.592

0.206

0.322

-0.013

HLS

-0.180

-0.405

-0.532

-0.163

0.241

0.287

HbA1c

-0.054

-0.007

0.137

-0.189

0.081

0.222

0.163

0.078

-0.268

0.036

0.108

0.027

0.063

0.019

-0.133

-0.298

-0.265

0.130

HDL-C

0.261

0.055

-0.608 *

0.161

0.003

-0.149

-0.095

-0.072

0.088

-0.439

-0.136

0.334