Supplementary Table 1
Changes in FPG, lipid profiles, body weight, and blood pressure after 12 weeks of treatment with sodium-glucose cotransporter-2 inhibitors as add-on therapy
dmj-43-590-s001.pdf
Supplementary Table 2
Changes in FPG, lipid profiles, body weight, and blood pressure after 12 weeks of treatment with sodium-glucose cotransporter-2 inhibitors as switch therapy
dmj-43-590-s002.pdf
Fig. 1Flow diagram of study subjects. SGLT2i, sodium-glucose cotransporter-2 inhibitor; HbA1c, glycosylated hemoglobin; OAD, oral anti-diabetic drug; MET, metformin; SU, sulfonylurea; DPP4i, dipeptidyl peptidase 4 inhibitor; TZD, thiazolidinedione.
Fig. 2Percentage of patients who achieved glycosylated hemoglobin (HbA1c) <7.0% in overall patients and those with baseline HbA1c <8.0%. aP<0.05 between add-on therapy and switch therapy.
Table 1Baseline demographic and clinical characteristics
Characteristic |
Overall (n=410) |
Add-on (n=207) |
Switch (n=203) |
P value |
Age, yr |
59.6±11.8 |
60.1±10.9 |
59.1±12.6 |
0.398 |
≥65 |
154 (37.6) |
77 (37.2) |
77 (37.9) |
0.878 |
Female sex |
236 (57.6) |
126 (60.9) |
110 (54.2) |
0.171 |
Height, cm |
161.6±8.5 |
161.3±7.9 |
161.8±9.1 |
0.612 |
Body weight, kg |
71.6±14.9 |
71.0±13.6 |
72.3±16.4 |
0.437 |
Body mass index, kg/m2
|
27.3±4.7 |
27.0±4.1 |
27.6±5.3 |
0.272 |
Systolic blood pressure, mm Hg |
130.3±13.5 |
131.5±13.5 |
129.0±13.4 |
0.075 |
Diastolic blood pressure, mm Hg |
77.7±9.8 |
78.7±9.6 |
76.6±9.8 |
0.052 |
Duration of diabetes, yr |
12.0±8.2 |
12.5±8.6 |
11.4±7.7 |
0.200 |
Insulin therapy |
154 (37.6) |
78 (37.7) |
76 (37.4) |
0.960 |
Titration of insulin dose (>10% of baseline) during SGLT2 inhibitor therapy |
31 (20.1) |
15 (19.2) |
16 (21.1) |
0.778 |
Subtype of SGLT2 inhibitor |
|
|
|
0.001 |
Dapagliflozin |
327 (79.8) |
179 (86.5) |
148 (72.9) |
Empagliflozin |
83 (20.2) |
28 (13.5) |
55 (27.1) |
HbA1c, % |
8.5±1.2 |
8.6±1.1 |
8.4±1.2 |
0.099 |
≥7.0% and <8.0% |
158 (38.5) |
70 (33.8) |
88 (44.4) |
0.047 |
≥8.0% and <9.0% |
137 (33.4) |
75 (36.2) |
62 (30.5) |
0.222 |
≥9.0% |
115 (28.0) |
62 (30.0) |
53 (26.1) |
0.386 |
Fasting plasma glucose, mg/dL |
156.6±42.6 |
164.8±42.4 |
148.4±41.3 |
<0.001 |
Total cholesterol, mg/dL |
152.6±29.2 |
153.4±29.2 |
151.8±29.2 |
0.571 |
Triglyceride, mg/dL |
156.4±96.6 |
161.1±110.5 |
151.7±80.0 |
0.330 |
HDL-C, mg/dL |
45.3±10.7 |
45.7±11.1 |
45.0±10.3 |
0.509 |
LDL-C, mg/dL |
82.1±24.2 |
81.6±22.5 |
82.7±25.9 |
0.664 |
Fasting C-peptide, ng/mL |
2.5±1.5 |
2.5±1.5 |
2.4±1.6 |
0.649 |
Fasting insulin, mIU/L |
14.7±7.7 |
15.8±8.5 |
12.6±6.1 |
0.341 |
HOMA-β |
65.0±37.5 |
64.6±40.1 |
65.7±34.6 |
0.948 |
HOMA-IR |
5.7±3.0 |
6.2±3.1 |
4.6±2.7 |
0.238 |
Aspartate aminotransferase, U/L |
31.0±18.3 |
30.4±17.7 |
31.6±19.0 |
0.506 |
Alanine aminotransferase, U/L |
35.8±27.4 |
35.6±28.6 |
36.0±26.1 |
0.907 |
Serum creatinine, mg/dL |
0.78±0.19 |
0.77±0.18 |
0.80±0.21 |
0.146 |
eGFR, mL/min/1.73 m2
|
91.1±22.8 |
91.8±22.9 |
90.5±22.8 |
0.582 |
Hypertension |
297 (72.4) |
151 (72.9) |
146 (71.9) |
0.816 |
Dyslipidemia |
348 (84.9) |
175 (84.5) |
173 (85.2) |
0.847 |
Cardiovascular disease |
94 (22.9) |
43 (20.8) |
51 (25.1) |
0.295 |
Medication |
|
|
|
|
Statin |
243 (83.7) |
173 (83.6) |
170 (83.7) |
0.963 |
Fenofibrate |
25 (6.1) |
13 (6.3) |
12 (5.9) |
0.876 |
Omega-3 fatty acid |
6 (1.5) |
4 (1.9) |
2 (1.0) |
0.425 |
ACEi/ARB |
246 (60.0) |
126 (60.9) |
120 (59.1) |
0.717 |
Anti-platelet agent |
223 (54.4) |
118 (57.0) |
105 (51.7) |
0.283 |
Table 2Changes in measurements after 12 weeks of treatment with sodium-glucose cotransporter-2 inhibitors
Variable |
Baseline |
Week 12 |
LS mean change from baseline (95% CI) |
Difference in LS mean change (95% CI)a
|
HbA1c, % |
|
|
|
|
Overall (n=410) |
8.5±0.1 |
7.8±0.1 |
−0.68 (−0.78 to −0.58)b
|
−0.52 (−0.68 to −0.37)c
|
Add-on (n=207) |
8.6±0.1 |
7.6±0.1 |
−0.94 (−1.05 to −0.83)b
|
|
Switch (n=203) |
8.4±0.1 |
8.0±0.1 |
−0.42 (−0.53 to −0.30)b
|
|
FPG, mg/dL |
|
|
|
|
Overall (n=410) |
156.6±2.1 |
131.5±1.6 |
−25.1 (−29.5 to −20.8)b
|
−10.5 (−16.6 to −4.4)c
|
Add-on (n=207) |
164.8±2.9 |
128.5±2.2 |
−30.3 (−34.6 to −26.1)b
|
|
Switch (n=203) |
148.4±2.9 |
134.5±2.3 |
−19.8 (−24.1 to −15.6)b
|
|
TG, mg/dL |
|
|
|
|
Overall (n=410) |
157.0±5.1 |
140.6±3.7 |
−16.5 (−24.2 to −8.7)b
|
−2.7 (−14.0 to 8.5) |
Add-on (n=207) |
160.8±8.1 |
141.0±5.3 |
−17.8 (−25.6 to −9.9)b
|
|
Switch (n=203) |
153.1±6.0 |
140.1±5.3 |
−15.1 (−23.1 to −7.1)b
|
|
HDL-C, mg/dL |
|
|
|
|
Overall (n=410) |
45.4±0.6 |
45.8±0.5 |
0.5 (−0.3 to −1.2) |
0.6 (−0.8 to 2.0) |
Add-on (n=207) |
45.7±0.8 |
46.4±0.7 |
0.8 (−0.2 to 1.7) |
|
Switch (n=203) |
45.0±0.8 |
45.2±0.8 |
0.1 (−0.8 to 1.1) |
|
LDL-C, mg/dL |
|
|
|
|
Overall (n=410) |
82.4±1.2 |
80.5±1.3 |
−1.9 (−4.1 to 0.3) |
2.0 (−2.0 to 6.0) |
Add-on (n=207) |
81.6±1.6 |
81.0±1.7 |
−0.9 (−3.7 to 1.9) |
|
Switch (n=203) |
83.2±1.9 |
80.0±1.9 |
−2.9 (−5.8 to 0.1) |
|
Body weight, kg |
|
|
|
|
Overall (n=410) |
74.6±1.2 |
72.5±1.1 |
−2.1 (−2.4 to −1.7)b
|
0.5 (−0.3 to 1.1) |
Add-on (n=207) |
74.1±1.5 |
72.3±1.5 |
−1.9 (−2.4 to −1.5)b
|
|
Switch (n=203) |
75.2±1.8 |
72.8±1.7 |
−2.4 (−2.8 to −1.9)b
|
|
SBP, mm Hg |
|
|
|
|
Overall (n=410) |
130.1±0.7 |
125.4±0.7 |
−4.7 (−6.1 to −3.3)b
|
1.1 (−1.3 to 3.5) |
Add-on (n=207) |
131.3±1.0 |
126.5±1.0 |
−4.2 (−5.9 to −2.6)b
|
|
Switch (n=203) |
128.8±1.0 |
124.2±1.0 |
−5.3 (−7.0 to −3.6)b
|
|
DBP, mm Hg |
|
|
|
|
Overall (n=410) |
78.7±0.7 |
77.3±1.0 |
−1.3 (−2.4 to −0.2)b
|
0.6 (−1.4 to 2.7) |
Add-on (n=207) |
78.4±0.7 |
77.1±1.0 |
−1.0 (−2.5 to 0.4) |
|
Switch (n=203) |
76.5±0.7 |
75.3±0.7 |
−1.7 (−3.2 to −0.2) |
|
eGFR, mL/min/1.73 m2
|
|
|
|
|
Overall (n=410) |
91.4±1.2 |
91.8±1.2 |
0.4 (−1.0 to 1.8) |
−1.9 (−4.7 to 0.8) |
Add-on (n=207) |
91.9±1.6 |
91.3±1.6 |
−0.6 (−2.6 to 1.4) |
|
Switch (n=203) |
90.8±1.7 |
92.3±1.8 |
1.5 (−0.4 to 3.5) |
|
Table 3Changes in glycosylated hemoglobin after 12 weeks of treatment with sodium-glucose cotransporter-2 inhibitors as add-on therapy and switch therapy
Variable |
Baseline |
Week 12 |
LS mean change from baseline (95% CI) |
Difference in LS mean change (95% CI)a
|
Add-on therapy |
|
|
|
|
Overall (n=207) |
8.6±0.1 |
7.6±0.1 |
−0.94 (−1.05 to −0.83)b
|
|
MET (n=58) |
7.8±0.1 |
7.0±0.1 |
−1.20 (−1.39 to −1.02)b
|
- |
MET+SU (n=19) |
8.1±0.2 |
7.1±0.1 |
−1.16 (−1.46 to −0.86)b
|
−0.05 (−0.51 to 0.42) |
MET+SU+DPP4i (n=52) |
8.9±0.2 |
7.7±0.1 |
−1.06 (−1.25 to −0.88)b
|
−0.14 (−0.50 to 0.22) |
Insulin (n=78) |
9.0±0.1 |
8.1±0.1 |
−0.71 (−0.86 to −0.56)b
|
−0.49 (−0.84 to −0.15)c
|
Switch therapy |
|
|
|
|
Overall (n=203) |
8.4±0.1 |
8.0±0.1 |
−0.42 (−0.53 to −0.30)b
|
|
DPP4i (n=114) |
8.2±0.1 |
8.0±0.1 |
−0.33 (−0.50 to −0.16)b
|
- |
SU (n=54) |
8.7±0.2 |
8.2±0.2 |
−0.42 (−0.67 to −0.18)b
|
0.09 (−0.28 to 0.46) |
TZD (n=35) |
8.3±0.1 |
7.9±0.2 |
−0.44 (−0.74 to −0.13)b
|
0.11 (−0.32 to 0.53) |
Table 4Comparison of clinical characteristics between the good responders and the poor responders in overall patients
Characteristic |
Good responder (n=171) |
Poor responder (n=239) |
P value |
Age, yr |
58.6±12.1 |
60.4±11.6 |
0.125 |
Female, sex |
97 (56.7) |
139 (58.2) |
0.839 |
Body mass index, kg/m2
|
27.6±4.9 |
27.0±4.5 |
0.264 |
Duration of diabetes, yr |
11.1±8.2 |
12.5±8.2 |
0.091 |
Subtype of SGLT2 inhibitor, dapagliflozin:empagliflozin |
137:34 |
190:49 |
0.901 |
Hypertension |
121 (70.8) |
176 (73.6) |
0.575 |
Dyslipidemia |
145 (84.8) |
203 (84.9) |
0.968 |
HbA1c, % |
8.8±1.3 |
8.3±1.0 |
<0.001 |
Fasting plasma glucose, mg/dL |
162.7±42.3 |
152.3±42.4 |
0.015 |
Fasting C-peptide, ng/mL |
2.6±1.6 |
2.5±1.4 |
0.609 |
Fasting insulin, mIU/L |
17.2±10.0 |
12.7±5.0 |
0.216 |
HOMA-β |
58.8±49.0 |
62.1±27.4 |
0.682 |
HOMA-IR |
7.1±3.6 |
4.6±2.0 |
0.044 |
eGFR, mL/min/1.73 m2
|
93.1±23.9 |
89.7±4.5 |
0.137 |
Insulin therapy |
54 (31.6) |
100 (41.8) |
0.039 |