parallel randomized trial

NCT06589765

A Phase 3, Randomized, Double-blinded Study to Evaluate the Efficacy and Safety of HRS-7535 Compared With Dapagliflozin in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (OUTSTAND-2)

Type 2 diabetes (adults)NCT06589765S000558

Design

Randomized: 810
Start year: 2024
Treatment: 52 weeks, follow-up 54 weeks
Countries: China (98 sites)
Sponsor: Jiangsu Hengrui Pharmaceuticals (industry)
Eligibility: age 18 to 75; HbA1c 7.5 to 11.0 percent; BMI 19 to 40; metformin monotherapy; eGFR 45 or more

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: randomized
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Safiglipron (HRS-7535) 30 mg tablet once daily Safiglipron 30 mg	metformin; lifestyle: not reported	202	179	178
A2	Safiglipron (HRS-7535) 60 mg tablet once daily Safiglipron 60 mg	metformin; lifestyle: not reported	203	171	168
A3	Safiglipron (HRS-7535) 90 mg tablet once daily Safiglipron 90 mg	metformin; lifestyle: not reported	203	168	167
A4	Dapagliflozin Dapagliflozin 10 mg	metformin; lifestyle: not reported	202	190	188

Baseline characteristics

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

Characteristic	Statistic	Safiglipron (HRS-7535) 30 mg tablet once daily A1	Safiglipron (HRS-7535) 60 mg tablet once daily A2	Safiglipron (HRS-7535) 90 mg tablet once daily A3	Dapagliflozin A4
age	mean (years)	52.8	52.1	52.0	52.0
age	sd (years)	10.81	10.46	10.80	10.75
bmi	mean (kg/m2)	26.97	27.07	27.27	27.18
bmi	sd (kg/m2)	3.59	3.74	3.43	4.04
diabetes duration	median (years)	5.54	4.21	4.47	4.97
diabetes duration	q1 (years)	2.9	2.0	2.4	2.7
diabetes duration	q3 (years)	8.1	8.7	9.0	8.1
egfr	mean (mL/min/1.73 m2)	104.72	105.31	104.92	105.73
egfr	sd (mL/min/1.73 m2)	14.42	12.99	15.78	14.57
female	n	67	73	77	72
female	percent	33.2	36.0	37.9	35.6
hba1c	mean (percent)	8.57	8.58	8.62	8.61
hba1c	sd (percent)	0.78	0.71	0.78	0.78
sbp	mean (mmHg)	124.57	125.31	125.48	123.12
sbp	sd (mmHg)	11.91	12.27	12.02	11.62
uacr	median (mg/g)	13.50	12.00	21.00	14.00
uacr	q1 (mg/g)	4.0	4.0	5.0	4.5
uacr	q3 (mg/g)	47.0	46.0	67.0	44.0
weight	mean (kg)	74.11	74.74	75.28	74.61
weight	sd (kg)	12.73	14.02	13.83	15.49

Analyses this trial contributes to

Results

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

HbA1c change (47 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
32	A1 vs A4	md	-0.32 percent	-0.61 to -0.03		hypothetical; randomized; diabetes_duration:more_than_5; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.37 percent	-0.63 to -0.10		hypothetical; randomized; sex:male; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.32 percent	-0.51 to -0.14		hypothetical; randomized; age:less_than_65; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.30 percent	-0.51 to -0.09		hypothetical; randomized; R0029347:Table 2
32	A1 vs A4	md	-0.16 percent	-0.52 to 0.21		hypothetical; randomized; sex:female; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.32 percent	-0.64 to -0.01		hypothetical; randomized; bmi:24_to_28; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.20 percent	-0.49 to 0.08		hypothetical; randomized; hba1c:8.5_or_less; R0029347:Extended Data Figure 2
32	A1	change	-1.58 percent	-1.73 to -1.43	179	hypothetical; randomized; R0029347:Table 2
32	A1 vs A4	md	-0.48 percent	-0.85 to -0.11		hypothetical; randomized; bmi:28_or_more; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.43 percent	-0.74 to -0.12		hypothetical; randomized; hba1c:more_than_8.5; R0029347:Extended Data Figure 2
32	A1	change	-1.58 percent	-1.72 to -1.45	186	treatment policy; randomized; R0029347:Table 2
32	A1 vs A4	md	0.09 percent	-0.40 to 0.58		hypothetical; randomized; bmi:less_than_24; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.24 percent	-0.71 to 0.23		hypothetical; randomized; age:65_or_more; R0029347:Extended Data Figure 2
32	A1 vs A4	md	-0.31 percent	-0.49 to -0.13		treatment policy; randomized; R0029347:Table 2
32	A1 vs A4	md	-0.30 percent	-0.61 to 0.02		hypothetical; randomized; diabetes_duration:5_or_less; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.12 percent	-0.63 to 0.38		hypothetical; randomized; age:65_or_more; R0029347:Extended Data Figure 2
32	A2	change	-1.42 percent	-1.56 to -1.27	183	treatment policy; randomized; R0029347:Table 2
32	A2 vs A4	md	0.00 percent	-0.32 to 0.31		hypothetical; randomized; diabetes_duration:more_than_5; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.14 percent	-0.34 to 0.06		treatment policy; randomized; R0029347:Table 2
32	A2 vs A4	md	-0.24 percent	-0.52 to 0.05		hypothetical; randomized; hba1c:8.5_or_less; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.22 percent	-0.44 to -0.01		hypothetical; randomized; R0029347:Table 2
32	A2 vs A4	md	-0.22 percent	-0.53 to 0.09		hypothetical; randomized; hba1c:more_than_8.5; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.22 percent	-0.58 to 0.14		hypothetical; randomized; sex:female; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.22 percent	-0.48 to 0.05		hypothetical; randomized; sex:male; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.39 percent	-0.69 to -0.10		hypothetical; randomized; diabetes_duration:5_or_less; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.25 percent	-0.44 to -0.07		hypothetical; randomized; age:less_than_65; R0029347:Extended Data Figure 2
32	A2	change	-1.50 percent	-1.66 to -1.35	171	hypothetical; randomized; R0029347:Table 2
32	A2 vs A4	md	-0.12 percent	-0.45 to 0.22		hypothetical; randomized; bmi:24_to_28; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.38 percent	-0.74 to -0.03		hypothetical; randomized; bmi:28_or_more; R0029347:Extended Data Figure 2
32	A2 vs A4	md	-0.14 percent	-0.61 to 0.32		hypothetical; randomized; bmi:less_than_24; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.40 percent	-0.89 to 0.09		hypothetical; randomized; age:65_or_more; R0029347:Extended Data Figure 2
32	A3	change	-1.68 percent	-1.84 to -1.53	168	hypothetical; randomized; R0029347:Table 2
32	A3 vs A4	md	-0.40 percent	-0.62 to -0.19		hypothetical; randomized; R0029347:Table 2
32	A3	change	-1.53 percent	-1.68 to -1.37	179	treatment policy; randomized; R0029347:Table 2
32	A3 vs A4	md	-0.25 percent	-0.45 to -0.05		treatment policy; randomized; R0029347:Table 2
32	A3 vs A4	md	-0.44 percent	-0.62 to -0.25		hypothetical; randomized; age:less_than_65; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.38 percent	-0.71 to -0.05		hypothetical; randomized; bmi:24_to_28; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.50 percent	-0.85 to -0.15		hypothetical; randomized; bmi:28_or_more; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.27 percent	-0.75 to 0.21		hypothetical; randomized; bmi:less_than_24; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.42 percent	-0.72 to -0.13		hypothetical; randomized; diabetes_duration:5_or_less; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.38 percent	-0.69 to -0.07		hypothetical; randomized; diabetes_duration:more_than_5; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.20 percent	-0.49 to 0.08		hypothetical; randomized; hba1c:8.5_or_less; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.63 percent	-0.94 to -0.33		hypothetical; randomized; hba1c:more_than_8.5; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.49 percent	-0.85 to -0.13		hypothetical; randomized; sex:female; R0029347:Extended Data Figure 2
32	A3 vs A4	md	-0.36 percent	-0.63 to -0.09		hypothetical; randomized; sex:male; R0029347:Extended Data Figure 2
32	A4	change	-1.28 percent	-1.43 to -1.13	190	hypothetical; randomized; R0029347:Table 2
32	A4	change	-1.27 percent	-1.40 to -1.15	193	treatment policy; randomized; R0029347:Table 2

HbA1c below 7 percent (14 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
32	A1 vs A4	or	2.19	1.39 to 3.45		hypothetical; randomized; R0029347:Table 2
32	A1 vs A4	or	1.84	1.18 to 2.87		treatment policy; randomized; R0029347:Extended Data Table 1
32	A1	responders	55.7	47.62 to 63.54	166	hypothetical; randomized; R0029347:Table 2
32	A1	responders	52.5	45.35 to 59.53	186	treatment policy; randomized; R0029347:Extended Data Table 1
32	A2	responders	54.9	46.42 to 63.11	143	hypothetical; randomized; R0029347:Table 2
32	A2	responders	48.8	41.71 to 55.86	183	treatment policy; randomized; R0029347:Extended Data Table 1
32	A2 vs A4	or	2.12	1.33 to 3.37		hypothetical; randomized; R0029347:Table 2
32	A2 vs A4	or	1.58	1.02 to 2.45		treatment policy; randomized; R0029347:Extended Data Table 1
32	A3	responders	53.7	46.58 to 60.70	179	treatment policy; randomized; R0029347:Extended Data Table 1
32	A3 vs A4	or	3.03	1.89 to 4.87		hypothetical; randomized; R0029347:Table 2
32	A3	responders	63.5	55.03 to 71.20	140	hypothetical; randomized; R0029347:Table 2
32	A3 vs A4	or	2.07	1.33 to 3.22		treatment policy; randomized; R0029347:Extended Data Table 1
32	A4	responders	36.5	29.49 to 44.06	182	hypothetical; randomized; R0029347:Table 2
32	A4	responders	38.1	31.39 to 45.20	193	treatment policy; randomized; R0029347:Extended Data Table 1

Level 2 or 3 hypoglycemia (participants) (8 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 202	not stated; safety; R0029347:Table 3
A1	events	3 / 202	not stated; safety; R0029347:Table 3
A2	events	0 / 202	not stated; safety; R0029347:Table 3
A2	events	3 / 202	not stated; safety; R0029347:Table 3
A3	events	0 / 203	not stated; safety; R0029347:Table 3
A3	events	4 / 203	not stated; safety; R0029347:Table 3
A4	events	0 / 202	not stated; safety; R0029347:Table 3
A4	events	0 / 202	not stated; safety; R0029347:Table 3

Systolic blood pressure change (4 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
32	A1	change	-2.93 mmHg	-4.40 to -1.46	166	hypothetical; randomized; R0029347:Results
32	A2	change	-3.67 mmHg	-5.23 to -2.11	143	hypothetical; randomized; R0029347:Results
32	A3	change	-4.53 mmHg	-6.10 to -2.97	140	hypothetical; randomized; R0029347:Results
32	A4	change	-4.61 mmHg	-6.03 to -3.20	183	hypothetical; randomized; R0029347:Results

Percent body weight change (14 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
32	A1	percent change	-2.35 percent		-2.92 to -1.78	167	hypothetical; randomized; R0029347:Table 2
32	A1 vs A4	md	1.25 percent		0.46 to 2.04		hypothetical; randomized; R0029347:Table 2
32	A1	percent change	-2.26 percent	0.32		187	treatment policy; randomized; R0029347:Extended Data Table 1
32	A1 vs A4	md	1.40 percent		0.53 to 2.27		treatment policy; randomized; R0029347:Extended Data Table 1
32	A2	percent change	-3.96 percent	0.32		183	treatment policy; randomized; R0029347:Extended Data Table 1
32	A2	percent change	-3.55 percent		-4.14 to -2.95	143	hypothetical; randomized; R0029347:Table 2
32	A2 vs A4	md	0.06 percent		-0.75 to 0.86		hypothetical; randomized; R0029347:Table 2
32	A2 vs A4	md	-0.30 percent		-1.18 to 0.57		treatment policy; randomized; R0029347:Extended Data Table 1
32	A3 vs A4	md	-0.72 percent		-1.59 to 0.16		treatment policy; randomized; R0029347:Extended Data Table 1
32	A3	percent change	-4.17 percent		-4.76 to -3.58	140	hypothetical; randomized; R0029347:Table 2
32	A3 vs A4	md	-0.56 percent		-1.37 to 0.24		hypothetical; randomized; R0029347:Table 2
32	A3	percent change	-4.37 percent	0.31		179	treatment policy; randomized; R0029347:Extended Data Table 1
32	A4	percent change	-3.60 percent		-4.15 to -3.05	183	hypothetical; randomized; R0029347:Table 2
32	A4	percent change	-3.66 percent	0.31		193	treatment policy; randomized; R0029347:Extended Data Table 1

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 202	not stated; safety; R0029347:Table 3
A2	events	0 / 202	not stated; safety; R0029347:Table 3
A3	events	1 / 203	not stated; safety; R0029347:Table 3
A4	events	0 / 202	not stated; safety; R0029347:Table 3

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	21 / 202	not stated; safety; R0029347:Table 3
A2	events	12 / 202	not stated; safety; R0029347:Table 3
A3	events	10 / 203	not stated; safety; R0029347:Table 3
A4	events	18 / 202	not stated; safety; R0029347:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	8 / 202	not stated; safety; R0029347:Table 3
A2	events	8 / 202	not stated; safety; R0029347:Table 3
A3	events	8 / 203	not stated; safety; R0029347:Table 3
A4	events	3 / 202	not stated; safety; R0029347:Table 3

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	46 / 202	not stated; safety; R0029347:Table 3
A2	events	77 / 202	not stated; safety; R0029347:Table 3
A3	events	95 / 203	not stated; safety; R0029347:Table 3
A4	events	14 / 202	not stated; safety; R0029347:Table 3

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	27 / 202	not stated; safety; R0029347:Table 3
A2	events	60 / 202	not stated; safety; R0029347:Table 3
A3	events	69 / 203	not stated; safety; R0029347:Table 3
A4	events	4 / 202	not stated; safety; R0029347:Table 3

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	27 / 202	not stated; safety; R0029347:Table 3
A2	events	39 / 202	not stated; safety; R0029347:Table 3
A3	events	47 / 203	not stated; safety; R0029347:Table 3
A4	events	13 / 202	not stated; safety; R0029347:Table 3

Constipation (4 lines; O27D)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	4.0	202	not stated; safety; R0029347:Extended Data Figure 5
A2	events	4.5	202	not stated; safety; R0029347:Extended Data Figure 5
A3	events	6.4	203	not stated; safety; R0029347:Extended Data Figure 5
A4	events	4.0	202	not stated; safety; R0029347:Extended Data Figure 5

Discontinuation due to gastrointestinal adverse events (4 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	6 / 202	not stated; safety; R0029347:Table 3
A2	events	7 / 202	not stated; safety; R0029347:Table 3
A3	events	7 / 203	not stated; safety; R0029347:Table 3
A4	events	0 / 202	not stated; safety; R0029347:Table 3

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 202	not stated; safety; R0029347:Table 3
A2	events	1 / 202	not stated; safety; R0029347:Table 3
A3	events	0 / 203	not stated; safety; R0029347:Table 3
A4	events	0 / 202	not stated; safety; R0029347:Table 3

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	19 / 202	not stated; safety; diabetic retinopathy; R0029347:Table 3
A2	events	22 / 202	not stated; safety; diabetic retinopathy; R0029347:Table 3
A3	events	17 / 203	not stated; safety; diabetic retinopathy; R0029347:Table 3
A4	events	26 / 202	not stated; safety; diabetic retinopathy; R0029347:Table 3