Saxagliptin for type 2 diabetes

Figures & data

Figure 1 Structure of saxagliptin and 5-hydroxy saxagliptin.^1,5

Figure 2 The incretins are released from intestinal cells after a meal, and act on pancreatic β-cells to stimulate insulin secretion. GLP-1 also acts on pancreatic α-cells to inhibit glucagon secretion and thereby reduce hepatic glucose production. The actions of the incretins are limited by DPP-4, which rapidly degrades GLP-1 and GIP into inactive fragments.^12–16 The presence of a DPP-4 inhibitor, such as saxagliptin, blocks degradation of the incretins, thereby increasing and prolonging their effects in the pancreas. As a result, blood glucose is lowered.^12,15 Reprinted from Gastroenterology, 132, Baggio LL, Biology of incretins: GLP-1 and GIP, 2131–57, © 2007,¹⁶ with permission from the AGA Institute.

Abbreviations: GLP-1, glucagon-like peptide-1; GIP, glucose-dependent insulinotropic peptide; DPP-4, dipeptidyl peptidase-4; GI, gastrointestinal.

Table 1 Summary of the effects of saxagliptin 5 mg on glycemic parameters in controlled 24-week clinical trials

Design	Treatment group	n	Baseline HbA1c (%)	Mean change in HbA1c (%)	Patients (%) with HbA1c <7%	Mean change in FPG (mmol/L)	Mean change in PPG-AUC (mmol·min/L)
Monotherapy^Citation6	Saxagliptin 5 mg	106	8.0	−0.5a	38	−0.50a	−2.39a
	Placebo	95	7.9	0.2	24	0.33	−0.33
Add-on to MET^Citation9	Saxagliptin 5 mg (+ MET)	191	8.1	−0.7a	44a	−1.22	−3.23
	Placebo (+ MET)	179	8.1	0.1	17	0.07	−1.00
Add-on to GLY^Citation10	Saxagliptin 5 mg (+ GLY)	253	8.5	−0.6a	23a	−0.56a	−1.89a
	GLY up-titration	267	8.4	0.08	9	0.06	0.44
Add-on to TZD^Citation11	Saxagliptin 5 mg (+ TZD)	186	8.4	−0.9a	42	−0.10	−4.00
	Placebo (+ TZD)	184	8.2	−0.3	26	−0.20	−1.00
Initial therapy with MET^Citation7	Saxagliptin 5 mg (+ MET)	320	9.4	−2.5a	60a	−3.33a	−7.66a
	MET	328	9.4	−2.0	41	−2.61	−5.38

a Note: Statistically significant.

Abbreviations: FPG, fasting plasma glucose; GLY, glyburide; HbA_1c, glycated hemoglobin; MET, metformin; PPG, postprandial glucose; TZD, thiazolidinedione.

Figure 3 Efficacy of saxagliptin in monotherapy, add-on combination therapy, or initial combination therapy in patients with T2D. Shown are the adjusted mean changes in HbA_1c with saxagliptin 5 mg once daily in the 24-week trials.^6,7,9–11

Notes: ^aStatistical significance versus placebo; ^bStatistical significance versus comparator.
Abbreviations: GLY, glyburide; HbA_1c, glycated hemoglobin; MET, metformin; TZD, thiazolidinedione.

Table 2 Incidence of common adverse events and hypoglycemia in controlled 24-week clinical trials with saxagliptin 5 mg

	Monotherapy^Citation6		Add-on to MET^Citation9		Add-on to GLY^Citation10		Add-on to TZD^Citation11		Initial combination with MET^Citation7
	SAXA 5 mg	Placebo	SAXA 5 mg (+MET)	Placebo (+MET)	SAXA 5 mg (+GLY)	Placebo +UP-GLY	SAXA 5 mg (+TZD)	Placebo (+TZD)	SAXA 5 mg (+MET)	MET
Adverse event, n (%)
n	106	95	191	179	253	267	186	184	320	328
Headache	10 (9.4)	7 (7.4)	11 (5.8)	13 (7.3)	19 (7.5)	15 (5.6)	10 (5.4)	7 (3.8)	24 (7.5)	17 (5.2)
Back pain	7 (6.6)	5 (5.3)	5 (2.6)	12 (6.7)	15 (5.9)	12 (4.5)	–	–	–	–
Diarrhea	1 (0.9)	3 (3.2)	11 (5.8)	20 (11.2)	10 (4.0)	16 (6.0)	–	–	22 (6.9)	24 (7.3)
Hypertension	–	–	4 (2.1)	6 (3.4)	16 (6.3)	6 (2.2)	8 (4.3)	9 (4.9)	15 (4.7)	11 (3.4)
Peripheral edema	–	–	–	–	–	–	15 (8.1)	8 (4.3)	–	–
Infections
URTI	9 (8.5)	11 (11.6)	9 (4.7)	9 (5.0)	16 (6.3)	18 (6.7)	17 (9.1)	13 (7.1)	–	–
UTI	9 (8.5)	4 (4.2)	10 (5.2)	8 (4.5)	27 (10.7)	22 (8.2)	12 (6.5)	12 (6.5)	–	–
Nasopharyngitis	6 (5.7)	6 (6.3)	13 (6.8)	14 (7.8)	15 (5.9)	18 (6.7)	9 (4.8)	11 (6.0)	22 (6.9)	13 (4.0)
Hypoglycemia
Reported casesa	5 (4.7)	6 (6.3)	10 (5.2)	9 (5.0)	37 (14.6)	27 (10.1)	5 (2.7)	7 (3.8)	11 (3.4)	13 (4.0)
Confirmed casesb	0 (0)	0 (0)	1 (0.5)	1 (0.6)	2 (0.8)	2 (0.7)	0 (0)	0 (0)	0 (0)	1 (0.3)

A dash (–) indicates that the incidence was not reported.

a Reported hypoglycemia was defined as events consistent with signs or symptoms of hypoglycemia with or without documented blood glucose levels.

b Confirmed hypoglycemia was defined by a fingerstick glucose value of ≤2.78 mmol/L with associated symptoms.

Abbreviations: GLY, glyburide; MET, metformin; PBO, placebo; SAXA, saxagliptin; TZD, thiazolidinedione; UP-GLY, uptitrated glyburide; URTI, upper respiratory tract infection; UTI, urinary tract infection.

Onglyza [package insert] Princeton, NJ/Wilmington, DE Bristol-Myers Squibb Company/AstraZeneca Pharmaceuticals LP 7 2009

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