parallel randomized trial

OUTSTAND-1

A Phase 3, Randomized, Double-blinded Study to Evaluate the Efficacy and Safety of HRS-7535 Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise (OUTSTAND-1)

Type 2 diabetes (adults)NCT06672172S000213

Design

Randomized: 284
Start year: 2024
Treatment: 52 weeks, follow-up 54 weeks
Countries: China (46 sites)
Sponsor: Jiangsu Hengrui Pharmaceuticals (industry)
Eligibility: age 18 to 75; HbA1c 7.0 to 10.0 percent; BMI 19.0 to 40.0; diet and exercise only

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: randomized
Missing data: retrieved dropout imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Safiglipron (HRS-7535) 30 mg tablet once daily Safiglipron 30 mg	diet and exercise; lifestyle: not reported	70	70	64
A2	Safiglipron (HRS-7535) 60 mg tablet once daily Safiglipron 60 mg	diet and exercise; lifestyle: not reported	70	70	60
A3	Safiglipron (HRS-7535) 90 mg tablet once daily Safiglipron 90 mg	diet and exercise; lifestyle: not reported	72	72	60
A4	Placebo Placebo	diet and exercise; lifestyle: not reported	72	72	59

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	Placebo A4	Whole trial ALL
age	mean (years)	48.7	48.9	50.3	49.7
age	sd (years)	8.9	10.2	10.2	10.2
asian	percent					100
bmi	mean (kg/m2)	27.7	27.9	27.4	28.3
bmi	sd (kg/m2)	3.4	3.6	3.9	3.9
diabetes duration	median (years)	1.8	1.3	1.7	1.3
diabetes duration	q1 (years)	0.6	0.5	0.6	0.4
diabetes duration	q3 (years)	3.2	2.7	3.1	3.1
female	n	29	21	20	24
female	percent	41.4	30.0	27.8	33.3
hba1c	mean (percent)	7.87	7.97	7.98	7.99
hba1c	sd (percent)	0.73	0.68	0.63	0.79
other prior glucose lowering drug	n	22	26	24	23
other prior glucose lowering drug	percent	31.4	37.1	33.3	31.9
sbp	mean (mmHg)	122.9	124.0	124.1	123.7
sbp	sd (mmHg)	11.1	11.7	11.9	11.1
waist	mean (cm)	95.7	97.5	96.7	97.9
waist	sd (cm)	9.1	9.8	11.1	9.5
weight	mean (kg)	76.3	77.9	77.6	78.0
weight	sd (kg)	11.2	14.8	16.2	13.5

Analyses this trial contributes to

Results

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

HbA1c change (46 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
32	A1 vs A4	md	-1.11 percent	-1.46 to -0.77		not stated; randomized; hba1c:<=8.5; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.46 percent	-1.91 to -1.00		not stated; randomized; bmi:>28; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.61 percent	-2.27 to -0.96		not stated; randomized; hba1c:>8.5; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-0.85 percent	-1.23 to -0.46		not stated; randomized; hba1c:<=8.0; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.04 percent	-1.50 to -0.57		not stated; randomized; bmi:24-28; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.22 percent	-1.54 to -0.91		not stated; randomized; age:<65; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.26 percent	-1.76 to -0.76		not stated; randomized; diabetes_duration:>2; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.22 percent	-1.62 to -0.83		not stated; randomized; diabetes_duration:<=2; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.22 percent	-1.53 to -0.91		treatment policy; randomized; R0011607:Table 2
32	A1	change	-1.40 percent	-1.61 to -1.18	70	treatment policy; randomized; R0011607:Table 2
32	A1 vs A4	md	-0.80 percent	-2.37 to 0.78		not stated; randomized; age:>=65; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.12 percent	-1.51 to -0.72		not stated; randomized; sex:male; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.73 percent	-2.22 to -1.25		not stated; randomized; hba1c:>8.0; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-0.87 percent	-1.79 to 0.04		not stated; randomized; bmi:<24; R0011607:Extended Data Figure 2
32	A1 vs A4	md	-1.38 percent	-1.87 to -0.89		not stated; randomized; sex:female; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.72 percent	-2.19 to -1.26		not stated; randomized; hba1c:>8.0; R0011607:Extended Data Figure 2
32	A2	change	-1.38 percent	-1.60 to -1.16	70	treatment policy; randomized; R0011607:Table 2
32	A2 vs A4	md	-1.20 percent	-1.52 to -0.89		treatment policy; randomized; R0011607:Table 2
32	A2 vs A4	md	-1.19 percent	-1.51 to -0.87		not stated; randomized; age:<65; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.42 percent	-2.82 to -0.02		not stated; randomized; age:>=65; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.41 percent	-2.27 to -0.55		not stated; randomized; bmi:<24; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.47 percent	-1.93 to -1.02		not stated; randomized; bmi:>28; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-0.84 percent	-1.33 to -0.35		not stated; randomized; bmi:24-28; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.16 percent	-1.56 to -0.76		not stated; randomized; diabetes_duration:<=2; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.29 percent	-1.80 to -0.78		not stated; randomized; diabetes_duration:>2; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-0.79 percent	-1.20 to -0.39		not stated; randomized; hba1c:<=8.0; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.12 percent	-1.47 to -0.77		not stated; randomized; hba1c:<=8.5; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.52 percent	-2.21 to -0.84		not stated; randomized; hba1c:>8.5; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.06 percent	-1.62 to -0.51		not stated; randomized; sex:female; R0011607:Extended Data Figure 2
32	A2 vs A4	md	-1.26 percent	-1.65 to -0.87		not stated; randomized; sex:male; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.05 percent	-1.45 to -0.65		not stated; randomized; hba1c:<=8.0; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.35 percent	-2.13 to -0.58		not stated; randomized; bmi:<24; R0011607:Extended Data Figure 2
32	A3	change	-1.63 percent	-1.84 to -1.41	72	treatment policy; randomized; R0011607:Table 2
32	A3 vs A4	md	-1.45 percent	-1.79 to -1.11		not stated; randomized; hba1c:<=8.5; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.26 percent	-2.50 to -0.02		not stated; randomized; age:>=65; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.44 percent	-1.81 to -1.08		not stated; randomized; sex:male; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.47 percent	-1.78 to -1.15		not stated; randomized; age:<65; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.94 percent	-2.39 to -1.50		not stated; randomized; hba1c:>8.0; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.45 percent	-1.75 to -1.14		treatment policy; randomized; R0011607:Table 2
32	A3 vs A4	md	-1.43 percent	-1.97 to -0.90		not stated; randomized; sex:female; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.39 percent	-1.78 to -1.00		not stated; randomized; diabetes_duration:<=2; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.35 percent	-1.84 to -0.86		not stated; randomized; bmi:24-28; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.40 percent	-2.09 to -0.71		not stated; randomized; hba1c:>8.5; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.56 percent	-2.05 to -1.07		not stated; randomized; diabetes_duration:>2; R0011607:Extended Data Figure 2
32	A3 vs A4	md	-1.57 percent	-2.01 to -1.12		not stated; randomized; bmi:>28; R0011607:Extended Data Figure 2
32	A4	change	-0.18 percent	-0.40 to 0.05	72	treatment policy; randomized; R0011607:Table 2

HbA1c below 7 percent (14 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
32	A1 vs A4	rd	46.4	31.87 to 60.99		treatment policy; randomized; R0011607:Table 2
32	A1	responders	83.5		61	hypothetical; randomized; R0011607:Extended Data Figure 3
32	A1	responders	71.4	59.38 to 81.60	70	treatment policy; randomized; R0011607:Table 2
32	A1 vs A4	or	17.17	5.96 to 49.50		treatment policy; randomized; R0011607:Table 2
32	A2	responders	77.1	65.55 to 86.33	70	treatment policy; randomized; R0011607:Table 2
32	A2 vs A4	or	29.51	9.85 to 88.39		treatment policy; randomized; R0011607:Table 2
32	A2 vs A4	rd	52.1	38.11 to 66.17		treatment policy; randomized; R0011607:Table 2
32	A2	responders	89.6		53	hypothetical; randomized; R0011607:Extended Data Figure 3
32	A3	responders	77.8	66.44 to 86.73	72	treatment policy; randomized; R0011607:Table 2
32	A3 vs A4	rd	52.8	38.91 to 66.64		treatment policy; randomized; R0011607:Table 2
32	A3	responders	86.6		54	hypothetical; randomized; R0011607:Extended Data Figure 3
32	A3 vs A4	or	27.76	10.01 to 77.04		treatment policy; randomized; R0011607:Table 2
32	A4	responders	25.0	15.54 to 36.60	72	treatment policy; randomized; R0011607:Table 2
32	A4	responders	14.8		53	hypothetical; randomized; R0011607:Extended Data Figure 3

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 70	not stated; safety; R0011607:Table 3
A2	events	0 / 70	not stated; safety; R0011607:Table 3
A3	events	0 / 72	not stated; safety; R0011607:Table 3
A4	events	0 / 72	not stated; safety; R0011607:Table 3

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Detail
32	A1 vs A4	md	-4.37 mmHg	-8.35 to -0.38	hypothetical; randomized; R0011607:Results
32	A2 vs A4	md	-4.24 mmHg	-8.34 to -0.14	hypothetical; randomized; R0011607:Results
32	A3 vs A4	md	-2.85 mmHg	-6.91 to 1.22	hypothetical; randomized; R0011607:Results

Percent body weight change (7 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
32	A1	percent change	-1.87 percent	-3.04 to -0.69	70	treatment policy; randomized; R0011607:Table 2
32	A1 vs A4	md	-0.65 percent	-2.21 to 0.91		treatment policy; randomized; R0011607:Table 2
32	A2	percent change	-3.45 percent	-4.64 to -2.25	70	treatment policy; randomized; R0011607:Table 2
32	A2 vs A4	md	-2.23 percent	-3.80 to -0.65		treatment policy; randomized; R0011607:Table 2
32	A3	percent change	-4.78 percent	-6.08 to -3.47	72	treatment policy; randomized; R0011607:Table 2
32	A3 vs A4	md	-3.56 percent	-5.22 to -1.89		treatment policy; randomized; R0011607:Table 2
32	A4	percent change	-1.22 percent	-2.42 to -0.02	72	treatment policy; randomized; R0011607:Table 2

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 70	not stated; safety; R0011607:Table 3
A2	events	0 / 70	not stated; safety; R0011607:Table 3
A3	events	0 / 72	not stated; safety; R0011607:Table 3
A4	events	0 / 72	not stated; safety; R0011607:Table 3

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	7 / 70	not stated; safety; R0011607:Table 3
A2	events	2 / 70	not stated; safety; R0011607:Table 3
A3	events	5 / 72	not stated; safety; R0011607:Table 3
A4	events	1 / 72	not stated; safety; R0011607:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	1 / 70	not stated; safety; R0011607:Table 3
A2	events	2 / 70	not stated; safety; R0011607:Table 3
A3	events	5 / 72	not stated; safety; R0011607:Table 3
A4	events	0 / 72	not stated; safety; R0011607:Table 3

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	18 / 70	not stated; safety; R0011607:Table 3
A2	events	25 / 70	not stated; safety; R0011607:Table 3
A3	events	33 / 72	not stated; safety; R0011607:Table 3
A4	events	5 / 72	not stated; safety; R0011607:Table 3

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	9 / 70	not stated; safety; R0011607:Table 3
A2	events	13 / 70	not stated; safety; R0011607:Table 3
A3	events	16 / 72	not stated; safety; R0011607:Table 3
A4	events	0 / 72	not stated; safety; R0011607:Table 3

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	15 / 70	not stated; safety; R0011607:Table 3
A2	events	14 / 70	not stated; safety; R0011607:Table 3
A3	events	21 / 72	not stated; safety; R0011607:Table 3
A4	events	3 / 72	not stated; safety; R0011607:Table 3

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 70	not stated; safety; R0011607:Table 3
A2	events	2 / 70	not stated; safety; R0011607:Table 3
A3	events	3 / 72	not stated; safety; R0011607:Table 3
A4	events	0 / 72	not stated; safety; R0011607:Table 3

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 70	not stated; safety; R0011607:Table 3
A2	events	0 / 70	not stated; safety; R0011607:Table 3
A3	events	0 / 72	not stated; safety; R0011607:Table 3
A4	events	0 / 72	not stated; safety; R0011607:Table 3