parallel randomized trial

NCT04998032

Efficacy and Safety of Once-weekly Supaglutide Versus Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Metformin: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

Type 2 diabetes (adults)NCT04998032S002121

Design

Randomized: 619
Start year: 2021
Treatment: 24 weeks, follow-up 24 weeks
Countries: China (61 sites)
Sponsor: Shanghai Yinnuo Pharmaceutical Technology Co., Ltd. (industry)
Eligibility: age 18 to 75; metformin monotherapy; HbA1c 7.5 to 10.5 at randomization; BMI 18.5 to 40; eGFR 60 or higher

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: modified itt
Missing data: MMRM with J2R for discontinuation and WOCF for rescue

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Efsubaglutide alfa 3 mg injection once weekly Phase 3 efsubaglutide alfa 3 mg weekly	metformin; lifestyle: not reported	171	171
A2	Placebo Placebo (phase 3)	metformin; lifestyle: not reported	173	173
A3	efsubaglutide alfa Efsubaglutide alfa 1 mg weekly (phase 2b)	metformin; lifestyle: not reported	40	40	37
A4	efsubaglutide alfa Efsubaglutide alfa 3 mg weekly (phase 2b)	metformin; lifestyle: not reported	40	40	39
A5	Placebo Placebo (phase 2b)	metformin; lifestyle: not reported	40	40	38

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Efsubaglutide alfa 3 mg injection once weekly A1	Placebo A2	Efsubaglutide alfa 1 mg weekly (phase 2b) A3	Efsubaglutide alfa 3 mg weekly (phase 2b) A4	Placebo A5
age	mean (years)	52.6	54.2	54.9	53.8	55.1
age	sd (years)	11.2	10.5	9.39	11.71	11.25
bmi	mean (kg/m2)	26.86	26.69	27.32	27.71	26.06
bmi	sd (kg/m2)	3.50	3.49	3.70	3.71	3.80
diabetes duration	mean (months)	41.52	42.34
diabetes duration	sd (months)	36.99	37.55
female	n	77	86	19	18	18
female	percent	45.0	49.7	47.5	45.0	45.0
hba1c	mean (percent)	8.67	8.66	8.55	8.54	8.80
hba1c	sd (percent)	0.76	0.75	0.54	0.76	0.90
sbp	mean (mmHg)	126.04	126.86	126.68	127.65	127.8
sbp	sd (mmHg)	11.64	11.93	9.89	13.58	10.62
waist	mean (cm)	95.22	94.4	96.26	95.54	93.40
waist	sd (cm)	9.35	9.48	11.17	7.87	9.42
weight	mean (kg)	73.60	72.46	75.57	76.65	70.42
weight	sd (kg)	12.72	13.09	14.25	11.26	15.05

Analyses this trial contributes to

Results

72 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (8 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
12	A3	change	-1.10 percent	-1.38 to -0.82	40	treatment policy; modified itt; R0006975:Supplement Table 2
12	A3 vs A5	md	-0.75 percent	-1.14 to -0.36		treatment policy; modified itt; R0006975:Supplement Table 2
12	A4	change	-1.43 percent	-1.70 to -1.16	40	treatment policy; modified itt; R0006975:Supplement Table 2
12	A4 vs A5	md	-1.08 percent	-1.47 to -0.69		treatment policy; modified itt; R0006975:Supplement Table 2
12	A5	change	-0.35 percent	-0.62 to -0.07	40	treatment policy; modified itt; R0006975:Supplement Table 2
24	A1	change	-1.80 percent	-2.01 to -1.59	171	treatment policy; modified itt; R0006975:Table 2
24	A1 vs A2	md	-1.06 percent	-1.37 to -0.74		treatment policy; modified itt; R0006975:Table 2
24	A2	change	-0.74 percent	-0.98 to -0.50	173	treatment policy; modified itt; R0006975:Table 2

Body weight change in kilograms (diabetes) (8 lines; O02)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
12	A3	change	-1.370 kg	-2.111 to -0.628	40	treatment policy; modified itt; R0006975:Supplement Table 2
12	A3 vs A5	md	-1.096 kg	-2.152 to -0.040		treatment policy; modified itt; R0006975:Supplement Table 2
12	A4	change	-1.793 kg	-2.518 to -1.067	40	treatment policy; modified itt; R0006975:Supplement Table 2
12	A4 vs A5	md	-1.519 kg	-2.568 to -0.470		treatment policy; modified itt; R0006975:Supplement Table 2
12	A5	change	-0.274 kg	-1.026 to 0.479	40	treatment policy; modified itt; R0006975:Supplement Table 2
24	A1	change	-2.74 kg	-3.39 to -2.09	171	treatment policy; modified itt; R0006975:Table 2
24	A1 vs A2	md	-1.82 kg	-2.78 to -0.85		treatment policy; modified itt; R0006975:Table 2
24	A2	change	-0.92 kg	-1.65 to -0.20	173	treatment policy; modified itt; R0006975:Table 2

HbA1c below 7 percent (8 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
12	A3	responders	32.6		40	treatment policy; modified itt; R0006975:Supplement Table 2
12	A3 vs A5	rd	25.1	8.4 to 41.8		treatment policy; modified itt; R0006975:Supplement Table 2
12	A4	responders	52.5		40	treatment policy; modified itt; R0006975:Supplement Table 2
12	A4 vs A5	rd	45.0	27.5 to 62.5		treatment policy; modified itt; R0006975:Supplement Table 2
12	A5	responders	7.5		40	treatment policy; modified itt; R0006975:Supplement Table 2
24	A1	responders	57.5		171	treatment policy; modified itt; R0006975:Table 2
24	A1 vs A2	rd	46.1	37.3 to 54.9		treatment policy; modified itt; R0006975:Table 2
24	A2	responders	11.4		173	treatment policy; modified itt; R0006975:Table 2

Level 2 or 3 hypoglycemia (participants) (10 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 171	not stated; safety; R0006975:Table 3
A1	events	0 / 171	not stated; safety; R0006975:Table 3
A2	events	0 / 173	not stated; safety; R0006975:Table 3
A2	events	0 / 173	not stated; safety; R0006975:Table 3
A3	events	0 / 40	not stated; safety; R0006975:Supplement Table 3
A3	events	0 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	0 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	0 / 40	not stated; safety; R0006975:Supplement Table 3
A5	events	0 / 40	not stated; safety; R0006975:Supplement Table 3
A5	events	0 / 40	not stated; safety; R0006975:Supplement Table 3

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1 vs A2	md	-0.96 mmHg	-3.33 to 1.41		treatment policy; modified itt; R0006975:Table 2
24	A1	change	-4.09 mmHg	-6.04 to -2.14	171	treatment policy; modified itt; R0006975:Table 2
24	A2	change	-3.65 mmHg	-4.61 to -2.69	173	treatment policy; modified itt; R0006975:Table 2

Serious adverse events (5 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	5 / 171	not stated; safety; R0006975:Table 3
A2	events	5 / 173	not stated; safety; R0006975:Table 3
A3	events	0 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	2 / 40	not stated; safety; R0006975:Supplement Table 3
A5	events	0 / 40	not stated; safety; R0006975:Supplement Table 3

Discontinuation due to adverse events (5 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	2 / 171	not stated; randomized; R0006975:Figure 1
A2	events	2 / 173	not stated; randomized; R0006975:Figure 1
A3	events	0 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	1 / 40	not stated; randomized; R0006975:Figure 1
A5	events	0 / 40	not stated; safety; R0006975:Supplement Table 3

Nausea (5 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	13 / 171	not stated; safety; R0006975:Table 3
A2	events	7 / 173	not stated; safety; R0006975:Table 3
A3	events	2 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	4 / 40	not stated; safety; R0006975:Supplement Table 3
A5	events	1 / 40	not stated; safety; R0006975:Supplement Table 3

Vomiting (5 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	17 / 171	not stated; safety; R0006975:Table 3
A2	events	3 / 173	not stated; safety; R0006975:Table 3
A3	events	2 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	2 / 40	not stated; safety; R0006975:Supplement Table 3
A5	events	0 / 40	not stated; safety; R0006975:Supplement Table 3

Diarrhea (5 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	37 / 171	not stated; safety; R0006975:Table 3
A2	events	6 / 173	not stated; safety; R0006975:Table 3
A3	events	2 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	4 / 40	not stated; safety; R0006975:Supplement Table 3
A5	events	0 / 40	not stated; safety; R0006975:Supplement Table 3

Constipation (5 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	6 / 171	not stated; safety; R0006975:Table 3
A2	events	3 / 173	not stated; safety; R0006975:Table 3
A3	events	1 / 40	not stated; safety; R0006975:Supplement Table 3
A4	events	2 / 40	not stated; safety; R0006975:Supplement Table 3
A5	events	0 / 40	not stated; safety; R0006975:Supplement Table 3

Acute pancreatitis (5 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 171	not stated; safety; pancreatitis; R0006975:Table 3
A2	events	0 / 173	not stated; safety; pancreatitis; R0006975:Table 3
A3	events	0 / 40	not stated; safety; pancreatitis; R0006975:Supplement Table 3
A4	events	0 / 40	not stated; safety; pancreatitis; R0006975:Supplement Table 3
A5	events	0 / 40	not stated; safety; pancreatitis; R0006975:Supplement Table 3