Glycemic control, weight-loss effects, and safety of cotadutide in individuals with type 2 diabetes: A systematic review and meta-analysis

Table 1 Characteristics of the randomized controlled trials and trial participants with type 2 diabetes evaluated in this meta-analysis, mean ± SD/median (interquartile range)

Ref.	Trial ID	Country	Phase of the trial	Major inclusion criteria	Trial arms (sample size, n)	Age (years)	Male (%)	Weight (kg)	BMI kg/m2	HbA1c (%)	Trial duration
Ambery et al[8]	NCT02548585	Germany	Phase 2a	Age: 18-65 years; HbA1c: 6.5%-8.5%; BMI: 27-40 kg/m2	MEDI0382 up to 200 μg (n = 25)	57.7 ± 6.0	52	95.9 ± 18.9	32.0 ± 4.4	7.2 ± 0.6	41 days
					Placebo (n = 26)	56.0 ± 7.2	58	99.9 ± 15.1	33.4 ± 3.4	7.3 ± 0.7
Asano et al[9]	NCT03645421	Japan	Phase 2a	Age: ≥20 years; HbA1c: 7%-10.5%; BMI: 24-40 kg/m2	Cotadutide 100 μg (n = 15)	56.7 ± 10.7	53	77.08 ± 14.21	28.82 ± 4.70	7.71 ± 0.44	48 days
					Cotadutide 200 μg (n = 15)	58.7 ± 11.3	87	73.05 ± 8.29	26.42 ± 1.81	8.2 ± 0.82
					Cotadutide 300 μg (n = 15)	57.5 ± 9.2	87	76.68 ± 9.97	26.99 ± 2.32	7.77 ± 0.85
					Placebo (n = 16)	60.0 ± 8.6	81	78.33 ± 12.8	28.53 ± 4.15	8.15 ± 0.90
Asano et al[10]	NCT04208620	Japan	Phase 1	Age: 20-74 years; HbA1c: 6.5%-8.5%; BMI: 25-35 kg/m2	Cotadutide 600 μg or HCTD (n = 12)	58.5 (34-69)	58.3	77.05 (62.3-84.8)	27.185 (25.21-34.71)	7.41 ± 0.67	10 weeks (70 days)
					Placebo (n = 4)	60.0 (46-63)	75.0	79.50 (69.8-80.5)	28.045 (26.17-32.12)	7.95 ± 0.45
Golubic et al[11]	NCT03596177	United Kingdom	Phase 2a	Age: 30-75 years; HbA1c: ≤ 8%; BMI: 28-40 kg/m2	Cotadutide 200 μg (n = 19)	59.5 ± 8.4	94.7	99.3 ± 10.8	32.2 ± 2.2	53 (5) mmol/mol	42 days
					Placebo (n = 9)	62.2 ± 7.2	77.8	101.4 ± 16.0	34.5 ± 2.8	50 (4) mmol/mol
Nahra et al[12]	NCT03235050	Eight countries	Phase 2b	Age: ≥18 years; HbA1c: 7%-10.5%; BMI: ≥ 25 kg/m2	Cotadutide 100 μg (n = 256)	57.6 ± 9.9	43	99.0 ± 20.3	35.0 ± 5.7	8.1 ± 0.9	54 weeks (378 days)
					Cotadutide 200 μg (n = 256)	57.3 ± 9.9	43	98.1 ± 20.2	34.9 ± 5.4	8.2 ± 1.0
					Cotadutide 300 μg (n = 256)	56.3 ± 10.2	50	100.8 ± 19.6	35.2 ± 5.4	8.1 ± 1.1
					Liraglutide 18 mg (n = 110)	55.5 ± 9.8	46	102.1 ± 22.7	35.4 ± 6.1	8.1 ± 1.0
					Placebo (n = 112)	57.3 ± 9.5	51	98.1 ± 19.8	34.2 ± 5.1	8.2 ± 1.1
Parker et al[13]	NCT03244800	Germany	Phase 2b	Age: ≥ 18 years; HbA1c: 6.5%-8.5%; BMI: 27-40 kg/m2	Cohort 1: Cotadutide 300 μg (n = 26)	58.7 ± 8.5	73	95.6 ± 17.2	31.5 ± 3.5	7.26 ± 0.58	49 days
					Cohort 1: Placebo (n = 13)	60.2 ± 5.6	69	93.8 ± 21.0	31.6 ± 3.8	7.19 ± 0.52
Parker et al[14]	NCT03550378	United Kingdom	Phase 2a	Age: 18-84 years; HbA1c: 6.5%-10.5%; BMI: 25-45 kg/m2; CKD (eGFR 30-59 mL/minute/1.73 m2)	Cotadutide 300 μg (n = 21)	71.1 ± 7.4	57.1	94.7 ± 17.6	32.4 ± 4.1	7.85 ± 0.7	32 days
					Placebo (n = 20)	70.9 ± 4.7	45	91.6 ± 15.8	32.9 ± 5.5	7.88 ± 1.3
Parker et al[15]	NCT03555994	Sweden and Netherlands	Phase 2a (Part A)	Age: ≥ 18 years; HbA1c: ≤ 8%; BMI: 27-40 kg/m2	Cotadutide 300 μg (n = 12)	65.8 ± 7.3	58	96.2 ± 7.7	31.8 ± 3.0	6.5 ± 0.6	28 days
					Placebo (n = 9)	69.3 ± 5.7	67	99.6 ± 20.1	32.7 ± 4.8	6.3 ± 0.7
			Phase 2a (Part B)	Similar to part A	Cotadutide 300 μg (n = 9)	61.8 ± 7.5	67	94.0 ± 14.6	31.9 ± 4.0	6.8 ± 0.66	35 days
					Placebo (n = 11)	64.0 ± 10.7	82	93.4 ± 11.8	30.08 ± 4.0	7.1 ± 0.63
					Liraglutide 1.8 mg (n = 10)	65.2 ± 9.1	60	91.5 ± 10.1	30.2 ± 2.3	6.8 ± 0.73
Selvarajah et al[16]	NCT04515849	Multiple countries	Phase 2b	Age: 18-79 years; HbA1c: 6.5%-12.5%; BMI: ≥ 25 kg/m2 (≥ 23 kg/m2 in Japan); CKD (eGFR 20-90 mL/minute/1.73 m2, UACR > 50 mg/mL)	Cotadutide 100 μg (n = 52)	67.2 ± 7.3	82.7	93.79 ± 19.94	32.15 ± 5.22	8 ± 1.07	14 weeks (98 days)
					Cotadutide 300 μg (n = 49)	65.7 ± 8.8	93.9	94.01 ± 18.79	32.26 ± 5.76	7.91 ± 1.1
					Cotadutide 600 μg (n = 51)	66.1 ± 7.4	80.4	93.69 ± 22.66	32.14 ± 5.65	8.1 ± 1.12
					Placebo (n = 51)	69.5 ± 7.3	74.5	93.15 ± 19.28	32.33 ± 6.05	7.84 ± 0.81
					Semaglutide 1 mg (n = 45)	67.0 ± 7.3	73.3	97.52 ± 19.45	34.41 ± 6.54	8.04 ± 1.18

HbA1c: Glycated hemoglobin; BMI: Body mass index; CKD: Chronic kidney disease; eGFR: Estimated glomerular filtration rate; UACR: Urinary albumin-to-creatinine ratio; HCTD: Highest clinically tolerated dose.