Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

Figures & data

Figure 1 Renal glucose transport.

Note: Both SGLT1 and SGLT2 reabsorb the filtered glucose, although the majority of glucose is reabsorbed by SGLT2.
Reproduced with permission: Vallon V. Am J of Physiol Cell Physiol. 2011;300(1):C6–C8.

Figure 2 At plasma glucose concentration around 8.3 mmol/liter, glucose appears in the urine.

Notes: After the saturation threshold of 13.3 mmol/liter, glucosuria increases linearly along with plasma glucose. SGLT2 inhibition promotes glucosuria at an earlier saturation threshold, permitting less reabsorption of glucose.
©2010 The Endocrine Society. Reproduced with permission from Nair S, Wilding JP. Sodium glucose co transporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab. 2010;95(1):34–42.⁴⁴ http://jcem.endojournals.org/.

Figure 3 Change from baseline in A_1c, percentage fasting plasma glucose concentration, and total body weight in dapagliflozin 2.5, 5 and 10 mg and placebo groups up to week 24. Reproduced with permission: Bailey et al. Lancet. 2010;375:2223–2233.

Figure 4 (A and B) Change in body mass component as measured by dual-energy X-ray absorptiometer fat mass and lean mass and Visceral Adipose Tissue (VAT) and Subcutaneous Adipose Tissue (SAT) volume as measured by magnetic resonance substudy, in type 2 diabetes patients inadequately controlled on metformin, randomized to dapagliflozin versus placebo.

©2012 The Endocrine Society. Reproduced with permission from Bolinder J et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012;97(3):20–31.47.²² http://jcem.endojournals.org/.

Figure 5 (A and B) Change in A_1c and body weight over a 52 week trial of type 2 diabetes patients uncontrolled on metformin randomized to glipizide versus dapagliflozin. Reproduced with permission: Nauck et al. Diabetes Care. 2011;34(9):2015–2022.

Figure 6 (A–C) Mean A_1c, Fasting Plasma Glucose (FPG) and change in body weight from baseline over 12 weeks in patients with type 2 diabetes receiving insulin plus insulin sensitizers, randomized to dapagliflozin versus placebo.

Reproduced with permission: Wilding JP et al. Diabetes Care. 2009;32(9):1656–1662.

Table 1 Efficacy of dapagliflozin in various studies

Study	Dapagliflozin dose	Placebo-corrected decrease in HbA1c (%)	Placebo-corrected achievement of goal HbA1c < 7% (%)	Placebo-corrected decrease in FPG (mmol/L)	Placebo-corrected decrease in PPBG (mmol/L)	Placebo-corrected weight reduction (kg)
Bailey et al	2.5, 5, 10 mg	0.37–0.54	7.1–14.7	0.66–0.97	N/A	1.3–2.0
Bolinder et al	10 mg	0.28	N/A	0.95	N/A	2.08
Ferranini et al	2.5, 5, 10 mg	0.35–0.66	9–19	0.62–1.37	N/A	0.6–1.1
List et al	2.5, 5, 10, 20, 50 mg	0.37–0.72	8–27	0.55–1.39	1.19–2.15	1.3–2.2
Nauck et al*	10 and 20 mg	0	4.6	0.20	N/A	4.65
Strojek et al	2.5, 5, 10 mg	0.45–0.69	17.3–18.7	1.07–1.47	1.45–1.61	0.46–1.54
Wilding et al	10 and 20 mg	0.70–0.78	N/A	0.85–1.52	2.94–3.36	2.4–2.6
Zhang et al+	10 and 20 mg	E, 0.3–0.5	N/A	N/A	N/A	E, 1.05–1.55
		L, 0.6–0.8				L, 2.75–3.5

Notes:

* Dapagliflozin was compared with glipizide, not placebo, in a noninferiority trial;

+ patients with type 2 diabetes divided into early and late stages.

Abbreviations: E, early, L, late; N/A, not available; FPG, fasting plasma glucose.

Nair S Wilding JP Sodium glucose co transporter 2 inhibitors as a new treatment for diabetes mellitus J Clin Endocrinol Metab 2010 95 1 34 42 http://jcem.endojournals.org/ 19892839

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Bolinder J Ljunggren O Kullberg J Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin J Clin Endocrinol Metab 2012 97 3 20 31 http://jcem.endojournals.org/

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