parallel randomized trial

ACHIEVE-3

A Phase 3, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Oral Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-3)

Type 2 diabetes (adults)NCT06045221S000438

Design

Randomized: 1,698
Start year: 2023
Treatment: 52 weeks, follow-up 57 weeks
Countries: Argentina, China, Japan, Mexico, United States
Sponsor: Eli Lilly and Company (industry)
Eligibility: adults T2D on metformin; HbA1c 7.0 to 10.5 percent

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Orforglipron 12 mg oral once daily Orforglipron 12 mg	metformin; lifestyle: not reported	424	326
A2	Orforglipron 36 mg oral once daily Orforglipron 36 mg	metformin; lifestyle: not reported	423	322
A3	Semaglutide 7 mg oral once daily (original tablet) Oral semaglutide 7 mg	metformin; lifestyle: not reported	426	325
A4	Semaglutide 14 mg oral once daily (original tablet) Oral semaglutide 14 mg	metformin; lifestyle: not reported	425	351

Baseline characteristics

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

Characteristic	Statistic	Orforglipron 12 mg oral once daily A1	Orforglipron 36 mg oral once daily A2	Semaglutide 7 mg oral once daily (original tablet) A3	Semaglutide 14 mg oral once daily (original tablet) A4	Whole trial ALL
age	mean (years)	54.0	53.4	54.9	53.4
age	sd (years)	11.3	11.4	11.2	10.5
asian	n	50	51	52	49
black	n	17	16	12	20
bmi	mean (kg/m2)					35.1
bmi	sd (kg/m2)					7.1
diabetes duration	mean (years)					8.7
diabetes duration	sd (years)					6.5
egfr	mean (mL/min/1.73 m2)					90.6
egfr	sd (mL/min/1.73 m2)					19.6
female	n	195	218	206	206
hba1c	mean (percent)	8.27	8.28	8.31	8.30
hba1c	sd (percent)	1.05	1.11	1.09	1.12
hispanic	n	304	304	316	310
other american indian alaska native	n	90	79	76	89
waist	mean (cm)					112.3
waist	sd (cm)					15.3
weight	mean (kg)					97.0
weight	sd (kg)					22.3
white	n	250	259	266	254

Analyses this trial contributes to

Results

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

HbA1c change (8 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-1.91 percent	0.058		326	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	md	-0.79 percent		-0.96 to -0.62		hypothetical; modified itt; registry:outcomes
52	A1 vs A4	md	-0.46 percent		-0.62 to -0.29		hypothetical; modified itt; registry:outcomes
52	A2	change	-2.16 percent	0.051		322	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	md	-1.04 percent		-1.2 to -0.88		hypothetical; modified itt; registry:outcomes
52	A2 vs A4	md	-0.71 percent		-0.86 to -0.55		hypothetical; modified itt; registry:outcomes
52	A3	change	-1.11 percent	0.063		325	hypothetical; modified itt; registry:outcomes
52	A4	change	-1.45 percent	0.061		351	hypothetical; modified itt; registry:outcomes

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-6.6 kg	0.34		331	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	md	-3.1 kg		-3.9 to -2.2		hypothetical; modified itt; registry:outcomes
52	A1 vs A4	md	-1.6 kg		-2.5 to -0.8		hypothetical; modified itt; registry:outcomes
52	A2	change	-8.9 kg	0.39		323	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	md	-5.4 kg		-6.3 to -4.4		hypothetical; modified itt; registry:outcomes
52	A2 vs A4	md	-3.9 kg		-4.9 to -3.0		hypothetical; modified itt; registry:outcomes
52	A3	change	-3.6 kg	0.26		325	hypothetical; modified itt; registry:outcomes
52	A4	change	-5.0 kg	0.29		356	hypothetical; modified itt; registry:outcomes

HbA1c below 7 percent (8 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	80.04 percent	1.97		424	hypothetical; randomized; registry:outcomes
52	A1 vs A3	rd	25.41		19.34 to 31.49		hypothetical; randomized; registry:outcomes
52	A1 vs A4	rd	13.92		8.10 to 19.74		hypothetical; randomized; registry:outcomes
52	A2	responders	85.41 percent	1.80		423	hypothetical; randomized; registry:outcomes
52	A2 vs A3	rd	30.78		24.78 to 36.78		hypothetical; randomized; registry:outcomes
52	A2 vs A4	rd	19.29		13.63 to 24.96		hypothetical; randomized; registry:outcomes
52	A3	responders	54.63 percent	2.45		426	hypothetical; randomized; registry:outcomes
52	A4	responders	66.12 percent	2.27		425	hypothetical; randomized; registry:outcomes

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 424	not stated; safety; hypoglycaemia; registry:adverse_events
A2	events	1 / 423	not stated; safety; hypoglycaemia; registry:adverse_events
A3	events	0 / 426	not stated; safety; hypoglycaemia; registry:adverse_events
A4	events	0 / 425	not stated; safety; hypoglycaemia; registry:adverse_events

Systolic blood pressure change (8 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-4.5 mmHg	0.55		331	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	md	-2.5 mmHg		-4.0 to -0.9		hypothetical; modified itt; registry:outcomes
52	A1 vs A4	md	-1.8 mmHg		-3.4 to -0.2		hypothetical; modified itt; registry:outcomes
52	A2	change	-5.4 mmHg	0.65		323	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	md	-3.4 mmHg		-5.1 to -1.7		hypothetical; modified itt; registry:outcomes
52	A2 vs A4	md	-2.7 mmHg		-4.5 to -1.0		hypothetical; modified itt; registry:outcomes
52	A3	change	-2.0 mmHg	0.58		325	hypothetical; modified itt; registry:outcomes
52	A4	change	-2.7 mmHg	0.59		356	hypothetical; modified itt; registry:outcomes

Percent body weight change (8 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	percent change	-6.7 percent	0.34		331	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	md	-2.9 percent		-3.8 to -2.1		hypothetical; modified itt; registry:outcomes
52	A1 vs A4	md	-1.4 percent		-2.3 to -0.5		hypothetical; modified itt; registry:outcomes
52	A2	percent change	-9.2 percent	0.40		323	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	md	-5.5 percent		-6.4 to -4.5		hypothetical; modified itt; registry:outcomes
52	A2 vs A4	md	-4.0 percent		-4.9 to -3.0		hypothetical; modified itt; registry:outcomes
52	A3	percent change	-3.7 percent	0.27		325	hypothetical; modified itt; registry:outcomes
52	A4	percent change	-5.3 percent	0.30		356	hypothetical; modified itt; registry:outcomes

Weight loss of 5 percent or more (8 lines; O11A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	59.18 percent	2.55		424	hypothetical; randomized; registry:outcomes
52	A1 vs A3	rd	22.29		15.16 to 29.42		hypothetical; randomized; registry:outcomes
52	A1 vs A4	rd	9.79		2.70 to 16.87		hypothetical; randomized; registry:outcomes
52	A2	responders	69.49 percent	2.39		423	hypothetical; randomized; registry:outcomes
52	A2 vs A3	rd	32.60		25.86 to 39.34		hypothetical; randomized; registry:outcomes
52	A2 vs A4	rd	20.09		13.21 to 26.98		hypothetical; randomized; registry:outcomes
52	A3	responders	36.89 percent	2.53		426	hypothetical; randomized; registry:outcomes
52	A4	responders	49.39 percent	2.57		425	hypothetical; randomized; registry:outcomes

Weight loss of 10 percent or more (8 lines; O11B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	28.23 percent	2.34		424	hypothetical; randomized; registry:outcomes
52	A1 vs A3	rd	15.05		9.20 to 20.90		hypothetical; randomized; registry:outcomes
52	A1 vs A4	rd	7.28		1.16 to 13.39		hypothetical; randomized; registry:outcomes
52	A2	responders	43.46 percent	2.54		423	hypothetical; randomized; registry:outcomes
52	A2 vs A3	rd	30.28		23.96 to 36.60		hypothetical; randomized; registry:outcomes
52	A2 vs A4	rd	22.5		16.13 to 28.88		hypothetical; randomized; registry:outcomes
52	A3	responders	13.18 percent	1.84		426	hypothetical; randomized; registry:outcomes
52	A4	responders	20.95 percent	2.08		425	hypothetical; randomized; registry:outcomes

Weight loss of 15 percent or more (8 lines; O11C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	11.99 percent	1.65		424	hypothetical; randomized; registry:outcomes
52	A1 vs A3	rd	7.00		3.08 to 10.93		hypothetical; randomized; registry:outcomes
52	A1 vs A4	rd	5.53		1.50 to 9.56		hypothetical; randomized; registry:outcomes
52	A2	responders	23.21 percent	2.17		423	hypothetical; randomized; registry:outcomes
52	A2 vs A3	rd	18.22		13.32 to 23.13		hypothetical; randomized; registry:outcomes
52	A2 vs A4	rd	16.76		11.86 to 21.65		hypothetical; randomized; registry:outcomes
52	A3	responders	4.99 percent	1.19		426	hypothetical; randomized; registry:outcomes
52	A4	responders	6.45 percent	1.25		425	hypothetical; randomized; registry:outcomes

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 424	not stated; safety; Acute kidney injury; registry:adverse_events
A2	events	1 / 423	not stated; safety; Acute kidney injury; registry:adverse_events
A3	events	1 / 426	not stated; safety; Acute kidney injury; registry:adverse_events
A4	events	1 / 425	not stated; safety; Acute kidney injury; registry:adverse_events

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 424	not stated; safety; registry:adverse_events
A2	events	1 / 423	not stated; safety; registry:adverse_events
A3	events	2 / 426	not stated; safety; registry:adverse_events
A4	events	0 / 425	not stated; safety; registry:adverse_events

SF-36 physical component summary change (8 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	2.88 points	0.333		329	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	md	0.01 points		-0.84 to 0.83		hypothetical; modified itt; registry:outcomes
52	A1 vs A4	md	0.32 points		-0.56 to 1.20		hypothetical; modified itt; registry:outcomes
52	A2 vs A4	md	0.01 points		-0.88 to 0.89		hypothetical; modified itt; registry:outcomes
52	A2	change	2.57 points	0.328		320	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	md	-0.32 points		-1.16 to 0.52		hypothetical; modified itt; registry:outcomes
52	A3	change	2.89 points	0.322		324	hypothetical; modified itt; registry:outcomes
52	A4	change	2.56 points	0.324		353	hypothetical; modified itt; registry:outcomes

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	21 / 424	not stated; safety; registry:adverse_events
A2	events	40 / 423	not stated; safety; registry:adverse_events
A3	events	19 / 426	not stated; safety; registry:adverse_events
A4	events	24 / 425	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	7 / 424	not stated; randomized; registry:flow
A2	events	4 / 423	not stated; randomized; registry:flow
A3	events	4 / 426	not stated; randomized; registry:flow
A4	events	5 / 425	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	112 / 424	not stated; safety; registry:adverse_events
A2	events	116 / 423	not stated; safety; registry:adverse_events
A3	events	56 / 426	not stated; safety; registry:adverse_events
A4	events	90 / 425	not stated; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	72 / 424	not stated; safety; registry:adverse_events
A2	events	70 / 423	not stated; safety; registry:adverse_events
A3	events	33 / 426	not stated; safety; registry:adverse_events
A4	events	44 / 425	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	92 / 424	not stated; safety; registry:adverse_events
A2	events	99 / 423	not stated; safety; registry:adverse_events
A3	events	56 / 426	not stated; safety; registry:adverse_events
A4	events	77 / 425	not stated; safety; registry:adverse_events

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	56 / 424	not stated; safety; registry:adverse_events
A2	events	55 / 423	not stated; safety; registry:adverse_events
A3	events	33 / 426	not stated; safety; registry:adverse_events
A4	events	38 / 425	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (12 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 424	not stated; safety; Cholelithiasis; registry:adverse_events
A1	events	0 / 424	not stated; safety; Cholecystitis chronic; registry:adverse_events
A1	events	0 / 424	not stated; safety; Cholecystitis; registry:adverse_events
A2	events	0 / 423	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	0 / 423	not stated; safety; Cholecystitis; registry:adverse_events
A2	events	1 / 423	not stated; safety; Cholecystitis chronic; registry:adverse_events
A3	events	0 / 426	not stated; safety; Cholelithiasis; registry:adverse_events
A3	events	0 / 426	not stated; safety; Cholecystitis chronic; registry:adverse_events
A3	events	1 / 426	not stated; safety; Cholecystitis; registry:adverse_events
A4	events	1 / 425	not stated; safety; Cholelithiasis; registry:adverse_events
A4	events	0 / 425	not stated; safety; Cholecystitis chronic; registry:adverse_events
A4	events	0 / 425	not stated; safety; Cholecystitis; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 424	not stated; safety; Pancreatitis acute; registry:adverse_events
A2	events	0 / 423	not stated; safety; Pancreatitis acute; registry:adverse_events
A3	events	0 / 426	not stated; safety; Pancreatitis acute; registry:adverse_events
A4	events	1 / 425	not stated; safety; Pancreatitis acute; registry:adverse_events

Thyroid cancer (any) (4 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 424	not stated; safety; Papillary thyroid cancer; registry:adverse_events
A2	events	0 / 423	not stated; safety; Papillary thyroid cancer; registry:adverse_events
A3	events	0 / 426	not stated; safety; Papillary thyroid cancer; registry:adverse_events
A4	events	1 / 425	not stated; safety; Papillary thyroid cancer; registry:adverse_events

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	57 / 424	not stated; safety; Diabetic retinopathy; registry:adverse_events
A2	events	60 / 423	not stated; safety; Diabetic retinopathy; registry:adverse_events
A3	events	54 / 426	not stated; safety; Diabetic retinopathy; registry:adverse_events
A4	events	58 / 425	not stated; safety; Diabetic retinopathy; registry:adverse_events

Suicidal ideation or behavior (8 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 424	not stated; safety; Suicidal ideation; registry:adverse_events
A1	events	0 / 424	not stated; safety; Suicide attempt; registry:adverse_events
A2	events	0 / 423	not stated; safety; Suicidal ideation; registry:adverse_events
A2	events	1 / 423	not stated; safety; Suicide attempt; registry:adverse_events
A3	events	0 / 426	not stated; safety; Suicidal ideation; registry:adverse_events
A3	events	0 / 426	not stated; safety; Suicide attempt; registry:adverse_events
A4	events	1 / 425	not stated; safety; Suicidal ideation; registry:adverse_events
A4	events	0 / 425	not stated; safety; Suicide attempt; registry:adverse_events

Intestinal obstruction or ileus (4 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 424	not stated; safety; Intestinal obstruction; registry:adverse_events
A2	events	0 / 423	not stated; safety; Intestinal obstruction; registry:adverse_events
A3	events	1 / 426	not stated; safety; Intestinal obstruction; registry:adverse_events
A4	events	0 / 425	not stated; safety; Intestinal obstruction; registry:adverse_events