Alogliptin in combination with metformin and pioglitazone for the treatment of type 2 diabetes mellitus

Figures & data

Figure 1 Chemical structure of alogliptin.

Table 1 Select efficacy outcomes from alogliptin clinical trials

Study	Pts (n)	Treatment		Treatment Period (weeks)	A1c change (%)	Achievement of A1c ≤7% (%)	FPG change (mg/dL)	BW change (kg)
		Background	Treatment group (intervention, mg)
Nauck et al^Citation20	527	MET ≥1,500 mg	PBO	26	−0.1	18	0	–
			ALO 12.5		−0.6a	52a	−19a	0.0b
			ALO 25		−0.6a	44a	−17a	−0.3b
Seino et al^Citation21	288	MET 500 or 750 mg	PBO	12	0.21	2.0	−0.80	−0.23
			ALO 12.5		−0.54a	28.3c	−19.0a	0.17c
			ALO 25		−0.64a	27.1c	−23.1a	−0.09
Rosenstock et al^Citation22	655	Drug naïve	ALO 25	26	−0.96	24.4	−25.2	−0.29
			PIO 30		−1.15	33.7	−37.8	2.19
			ALO 12.5 + PIO 30		−1.56d	53.4d	−48.6d	2.51
			ALO 25 + PIO 30		−1.71d,e	62.8d,e	−50.5d,e	3.14d,e
Kaku et al^Citation23	339	PIO 15–30 mg	PBO	12	−0.19	20g	−2.4	−0.03
			ALO 12.5		−0.91f	49.5f,g	−14.9f	0.48f
			ALO 25		−0.97f	49.6f,g	−18.9f	0.46f
DeFronzo et al^Citation24	1,554	MET ≥1,500 mg	PIO 15–45	26	−0.9	30.5	−28.8	1.5
			PIO 15–45 + ALO 12.5		−1.4h	54.6h	−45.0h	1.8
			PIO 15–45 + ALO 25		−1.4h	55.9h	−45.0h	1.9
Bosi et al^Citation25	803	MET ≥1,500 mg or MTD	PIO 45	52	−0.29	21.3	−3.6	1.6
			PIO 30 + ALO 25		−0.70h	33.2h	−14.4h	1.1
Pratley et al^Citation26	493	PIO ± MET/SU	PBO	26	−0.19	34.0	−5.7	–
			ALO 12.5		−0.66a	44.2i	−19.7j	0.42b
			ALO 25		−0.80a	49.2i	−19.9j	0.05b

Notes:

a P<0.001 versus placebo

b least-squares mean difference relative to placebo

c statistically significant versus change with MET monotherapy

d P<0.05 versus PIO 30

e P<0.05 versus ALO 25

f P<0.05 versus PBO

g Goal A1c threshold of <6.9%

h P<0.001 versus PIO alone

i P≤0.016 versus placebo

j P<0.003 versus placebo.

Abbreviations: A1c, glycosylated hemoglobin; ALO, alogliptin; BW, body weight; FPG, fasting plasma glucose; MET, metformin; MTD, maximum tolerated dose; PBO, placebo; PIO, pioglitazone; PPG, postprandial glucose; Pts, participants randomized; SU, sulfonylurea.

Table 2 Select adverse-drug-event rates from selected alogliptin clinical trials

Study	Treatment group (intervention, mg)	Discontinuation due to AE (n [%])	Diarrhea (n [%])	Nasopharyngitis (n [%])	Arthralgia (n [%])	Headache (n [%])	Severe hypoglycemia (n [%])	Peripheral edema (n [%])
Nauck et al^Citation20	MET + PBO	1 (1)	6 (6)	6 (6)	5 (5)	2 (2)	0 (0)	NR
	MET + ALO 12.5	7 (3)	6 (3)	12 (6)	4 (2)	8 (4)	0 (0)	NR
	MET + ALO 25	4 (2)	7 (3)	7 (3)	3 (1)	4 (2)	0 (0)	NR
Seino et al^Citation21	MET + PBO	0 (0)	1 (1)	20 (20.0)	0 (0)	0 (0)	0 (0)	NR
	MET + ALO 12.5	0 (0)	5 (5.4)	18 (19.6)	0 (0)	6 (6.5)	0 (0)	NR
	MET + ALO 25	0 (0)	1 (1)	22 (22.9)	1 (1)	0 (0)	0 (0)	NR
Kaku et al^Citation23	PIO + PBO	4 (3.5)	NR	6 (5.2)	NR	NR	0 (0)	2 (1.7)
	PIO + ALO 12.5	1 (0.9)	NR	5 (4.5)	2 (1.8)	NR	0 (0)	0 (0)
	PIO + ALO 25	2 (1.8)	NR	(12.4)	(9.1)	NR	0 (0)	(2.7)
DeFronzo et al^Citation24	MET + PIO + PBO	11 (2.8)	14 (3.6)	11 (2.8)	13 (3.4)	23 (5.9)	2 (0.5)	10 (2.6)
	MET + PIO + ALO 12.5	8 (2.1)	9 (2.3)	19 (4.9)	11 (2.8)	13 (3.3)	0 (0)	10 (2.6)
	MET + PIO + ALO 25	6 (1.5)	20 (5.1)	21 (5.4)	12 (3.1)	14 (3.6)	1 (0.3)	14 (3.6)
Bosi et al^Citation25	MET + PIO 30 + ALO 25	12 (3.0)	11 (2.7)	28 (6.9)	13 (3.2)	19 (4.7)	2 (0.5)	16 (4.0)
	MET + PIO 45	16 (4.0)	24 (6.0)	21 (5.3)	13 (3.3)	16 (4.0)	0 (0)	18 (4.5)
Pratley et al^Citation26	PIO + PBO ± MET/SU	3 (3.1)	NR	6 (6.2)	NR	4 (4.1)	NR	7 (7.2)
	PIO + ALO 12.5 ± MET/SU	6 (3.0)	NR	8 (4.0)	NR	8 (4.0)	NR	12 (6.1)
	PIO + ALO 25 ± MET/SU	6 (3.0)	NR	14 (7.0)	NR	10 (5.0)	NR	11 (5.5)

Abbreviations: AE, adverse event; ALO, alogliptin; MET, metformin; NR, not reported; PBO, placebo; PIO, pioglitazone; SU, sulfonylurea.

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