J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Letter to the Editor

Volume 9, Number 5, May 2017, pages 446-448

What Properties of Sodium-Glucose Cotransporter 2 Inhibitors Determine the Improvement in Hemoglobin A1c and Body Weight?

Figure 1. Daily standard dose (a), maximum plasma concentration (b), SGLT2 inhibitory concentration 50% value (c) and SGLT2 selectivity (d) of each SGLT2i. The data in (a) were obtained by the interview form of each SGLT2i produced in Japan, data in (b) and (c) were obtained from the article by Nishiyama et al [5], and data in (d) were obtained from the article by Suzuki et al [6].

**Table 1.** Changes in HbA1c and Body Weight in Patients With Type 2 Diabetes
SGLT2 inhibitors	Changes in HbA1c (%)	Changes in HbA1c in patients with moderate renal insufficiency after 24 weeks	Changes in body weight (kg)
Dapagliflozin	-0.37	-0.41	41	30 ≤ eGFR < 45	5	-0.47	-2.06	-2.13
			35	45 ≤ eGFR < 60	5	-0.47
Empagliflozin	-0.4	-0.65	96	30 ≤ eGFR < 45	25	-0.21	-1.7	-1.93
			91	45 ≤ eGFR < 60	25	-0.54
Canagliflozin	-0.8	-0.74	2	45 ≤ eGFR < 60	100	-0.79	-2.53	-2.6
Ipragliflozin	-0.7	-0.87	58	30 ≤ eGFR < 60	50	-0.28	-1.42	-2.38
Luseogliflozin	-0.39	-0.63	95	30 ≤ eGFR < 60	2.5	-0.11	-1.31	-2.7
Tofogliflozin	-0.77	-1.02	30	30 ≤ eGFR < 60	20	-0.24	Not determined	-2.72

Table 1. Changes in HbA1c and Body Weight in Patients With Type 2 Diabetes

SGLT2 inhibitors

Changes in HbA1c (%)

Changes in HbA1c in patients with moderate renal insufficiency after 24 weeks

Changes in body weight (kg)

After 12 weeks

After 24 weeks

eGFR (mL/min/1.73 m²)

Daily dose (mg)

ΔHbA1c (%)

After 12 weeks

After 24 weeks

Dapagliflozin

-0.37

-0.41

30 ≤ eGFR < 45

-0.47

-2.06

-2.13

45 ≤ eGFR < 60

-0.47

Empagliflozin

-0.4

-0.65

30 ≤ eGFR < 45

-0.21

-1.7

-1.93

45 ≤ eGFR < 60

-0.54

Canagliflozin

-0.8

-0.74

45 ≤ eGFR < 60

100

-0.79

-2.53

-2.6

Ipragliflozin

-0.7

-0.87

30 ≤ eGFR < 60

-0.28

-1.42

-2.38

Luseogliflozin

-0.39

-0.63

30 ≤ eGFR < 60

2.5

-0.11

-1.31

-2.7

Tofogliflozin

-0.77

-1.02

30 ≤ eGFR < 60

-0.24

Not determined

-2.72

**Table 2.** Correlation Between Changes in HbA1c and Body Weight by SGLT2i and Pharmacokinetic Parameters of SGLT2i
	Changes in HbA1c after 12 weeks	Changes in HbA1c after 24 weeks	Changes in body weight after 12 weeks	Changes in body weight after 24 weeks	Changes in HbA1c after 12 weeks in patients with moderate renal insufficiency
Changes in HbA1c after 12 weeks	-	-	0.805	0.053	0.427	0.473	0.562	0.246	0.353	0.492
Changes in HbA1c after 24 weeks	0.805	0.053	-	-	-0.21	0.735	0.546	0.262	-0.208	0.693
Changes in body weight after 12 weeks	0.427	0.473	-0.21	0.735	-	-	-0.024	0.969	0.977	0.004
Changes in body weight after 24 weeks	0.562	0.246	0.546	0.262	-0.024	0.969	-	-	-0.16	0.762
Changes in HbA1c after 12 weeks in patients with moderate renal insufficiency	0.353	0.492	-0.208	0.693	0.977	0.004	-0.16	0.762	-	-
Maximal plasma concentration (MC)	-0.834	0.039	-0.755	0.083	0.008	0.99	-0.31	0.55	-0.112	0.833
SGLT2 inhibitory concentration 50% (IC50)	-0.59	0.218	-0.57	0.238	0.203	0.744	-0.099	0.853	-0.036	0.945
IC50 adjusted by the lowest potency (potency)	0.639	0.172	0.755	0.083	-0.175	0.778	0.308	0.552	-0.016	0.977
MC × potency	-0.931	0.007	-0.865	0.026	-0.422	0.479	-0.53	0.279	-0.162	0.76
Area under the blood concentration time curve (AUC) (ng × h/mL)	-0.818	0.047	-0.512	0.299	-0.335	0.581	-0.33	0.523	-0.506	0.306
Selectivity	-0.156	0.768	-0.605	0.203	0.876	0.051	-0.459	0.36	0.669	0.146

Table 2. Correlation Between Changes in HbA1c and Body Weight by SGLT2i and Pharmacokinetic Parameters of SGLT2i

Changes in HbA1c after 12 weeks

Changes in HbA1c after 24 weeks

Changes in body weight after 12 weeks

Changes in body weight after 24 weeks

Changes in HbA1c after 12 weeks in patients with moderate renal insufficiency

P value

Changes in HbA1c after 12 weeks

0.805

0.053

0.427

0.473

0.562

0.246

0.353

0.492

Changes in HbA1c after 24 weeks

0.805

0.053

-0.21

0.735

0.546

0.262

-0.208

0.693

Changes in body weight after 12 weeks

0.427

0.473

-0.21

0.735

-0.024

0.969

0.977

0.004

Changes in body weight after 24 weeks

0.562

0.246

0.546

0.262

-0.024

0.969

-0.16

0.762

Changes in HbA1c after 12 weeks in patients with moderate renal insufficiency

0.353

0.492

-0.208

0.693

0.977

0.004

-0.16

0.762

Maximal plasma concentration (MC)

-0.834

0.039

-0.755

0.083

0.008

0.99

-0.31

0.55

-0.112

0.833

SGLT2 inhibitory concentration 50% (IC50)

-0.59

0.218

-0.57

0.238

0.203

0.744

-0.099

0.853

-0.036

0.945

IC50 adjusted by the lowest potency (potency)

0.639

0.172

0.755

0.083

-0.175

0.778

0.308

0.552

-0.016

0.977

MC × potency

-0.931

0.007

-0.865

0.026

-0.422

0.479

-0.53

0.279

-0.162

0.76

Area under the blood concentration time curve (AUC) (ng × h/mL)

-0.818

0.047

-0.512

0.299

-0.335

0.581

-0.33

0.523

-0.506

0.306

Selectivity

-0.156

0.768

-0.605

0.203

0.876

0.051

-0.459

0.36

0.669

0.146