parallel randomized trial

ACHIEVE-1

A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone

Type 2 diabetes (adults)NCT05971940S001950

Design

Randomized: 559
Start year: 2023
Treatment: 40 weeks, follow-up 42 weeks
Countries: China, India, Japan, Mexico, United States
Sponsor: Eli Lilly and Company (industry)
Eligibility: adults with type 2 diabetes on diet and exercise alone; HbA1c 7.0 to 9.5 percent

Conduct and analysis

Blinding: double blind
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	Placebo Placebo	diet and exercise; lifestyle: not reported	138	138
A2	Orforglipron 3 mg oral once daily Orforglipron 3 mg	diet and exercise; lifestyle: not reported	143	143
A3	Orforglipron 12 mg oral once daily Orforglipron 12 mg	diet and exercise; lifestyle: not reported	137	137
A4	Orforglipron 36 mg oral once daily Orforglipron 36 mg	diet and exercise; lifestyle: not reported	141	141

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Orforglipron 3 mg oral once daily A2	Orforglipron 12 mg oral once daily A3	Orforglipron 36 mg oral once daily A4	Whole trial ALL
age	mean (years)	53.3	53.3	54.1	52.8
age	sd (years)	12.51	11.28	11.76	11.83
asian	n	61	63	59	62
black	n	3	8	9	4
diabetes duration	mean (years)					4.4
female	n	63	63	71	72
hba1c	mean (percent)	7.96	7.93	7.98	8.07
hba1c	sd (percent)	0.89	0.86	0.91	0.90
hispanic	n	56	57	55	55
other race american indian alaska native	n	35	35	38	35
other race multiple	n	0	0	1	0
weight	mean (kg)					90.2
white	n	38	37	30	40

Analyses this trial contributes to

Results

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

HbA1c change (7 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-0.15 percent	0.113		138	hypothetical; modified itt; registry:outcomes
40	A2	change	-1.26 percent	0.114		143	hypothetical; modified itt; registry:outcomes
40	A2 vs A1	md	-1.12 percent		-1.43 to -0.80		hypothetical; modified itt; registry:outcomes
40	A3	change	-1.59 percent	0.087		137	hypothetical; modified itt; registry:outcomes
40	A3 vs A1	md	-1.44 percent		-1.72 to -1.16		hypothetical; modified itt; registry:outcomes
40	A4	change	-1.45 percent	0.104		141	hypothetical; modified itt; registry:outcomes
40	A4 vs A1	md	-1.30 percent		-1.61 to -1.00		hypothetical; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (7 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-1.3 kg	0.36		138	hypothetical; modified itt; registry:outcomes
40	A2	change	-4.4 kg	0.43		143	hypothetical; modified itt; registry:outcomes
40	A2 vs A1	md	-3.1 kg		-4.2 to -2.0		hypothetical; modified itt; registry:outcomes
40	A3	change	-5.5 kg	0.49		137	hypothetical; modified itt; registry:outcomes
40	A3 vs A1	md	-4.2 kg		-5.5 to -3.0		hypothetical; modified itt; registry:outcomes
40	A4	change	-7.3 kg	0.55		141	hypothetical; modified itt; registry:outcomes
40	A4 vs A1	md	-6.0 kg		-7.3 to -4.6		hypothetical; modified itt; registry:outcomes

HbA1c below 7 percent (7 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	responders	37.11		97	hypothetical; modified itt; registry:outcomes
40	A2	responders	78.15		119	hypothetical; modified itt; registry:outcomes
40	A2 vs A1	rd	44.90	34.41 to 55.39		hypothetical; modified itt; registry:outcomes
40	A3	responders	81.25		112	hypothetical; modified itt; registry:outcomes
40	A3 vs A1	rd	48.22	37.50 to 58.93		hypothetical; modified itt; registry:outcomes
40	A4	responders	78.99		119	hypothetical; modified itt; registry:outcomes
40	A4 vs A1	rd	46.94	36.61 to 57.28		hypothetical; modified itt; registry:outcomes

Systolic blood pressure change (7 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-0.5 mmHg	0.88		138	hypothetical; modified itt; registry:outcomes
40	A2	change	-3.2 mmHg	0.91		143	hypothetical; modified itt; registry:outcomes
40	A2 vs A1	md	-2.7 mmHg		-5.2 to -0.2		hypothetical; modified itt; registry:outcomes
40	A3	change	-6.1 mmHg	0.97		137	hypothetical; modified itt; registry:outcomes
40	A3 vs A1	md	-5.6 mmHg		-8.2 to -3.0		hypothetical; modified itt; registry:outcomes
40	A4	change	-6.0 mmHg	0.91		141	hypothetical; modified itt; registry:outcomes
40	A4 vs A1	md	-5.5 mmHg		-8.0 to -3.0		hypothetical; modified itt; registry:outcomes

Percent body weight change (7 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	percent change	-1.6 percent	0.43		138	hypothetical; modified itt; registry:outcomes
40	A2	percent change	-4.7 percent	0.47		143	hypothetical; modified itt; registry:outcomes
40	A2 vs A1	md	-3.1 percent		-4.4 to -1.8		hypothetical; modified itt; registry:outcomes
40	A3	percent change	-6.1 percent	0.55		137	hypothetical; modified itt; registry:outcomes
40	A3 vs A1	md	-4.5 percent		-5.9 to -3.1		hypothetical; modified itt; registry:outcomes
40	A4	percent change	-7.9 percent	0.58		141	hypothetical; modified itt; registry:outcomes
40	A4 vs A1	md	-6.3 percent		-7.7 to -4.8		hypothetical; modified itt; registry:outcomes

Weight loss of 5 percent or more (7 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	responders	14.58		96	hypothetical; modified itt; registry:outcomes
40	A2	responders	47.06		119	hypothetical; modified itt; registry:outcomes
40	A2 vs A1	rd	25.36	14.25 to 36.47		hypothetical; modified itt; registry:outcomes
40	A3	responders	58.56		111	hypothetical; modified itt; registry:outcomes
40	A3 vs A1	rd	37.28	26.05 to 48.50		hypothetical; modified itt; registry:outcomes
40	A4	responders	66.39		119	hypothetical; modified itt; registry:outcomes
40	A4 vs A1	rd	44.80	33.54 to 56.06		hypothetical; modified itt; registry:outcomes

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 138	not stated; safety; registry:adverse_events
A2	events	1 / 143	not stated; safety; registry:adverse_events
A3	events	0 / 137	not stated; safety; registry:adverse_events
A4	events	1 / 141	not stated; safety; registry:adverse_events

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 138	not stated; safety; registry:adverse_events
A2	events	2 / 143	not stated; safety; registry:adverse_events
A3	events	1 / 137	not stated; safety; registry:adverse_events
A4	events	0 / 141	not stated; safety; registry:adverse_events

Hospitalization for heart failure (4 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 138	not stated; safety; cardiac failure; registry:adverse_events
A2	events	0 / 143	not stated; safety; cardiac failure; registry:adverse_events
A3	events	1 / 137	not stated; safety; cardiac failure; registry:adverse_events
A4	events	0 / 141	not stated; safety; cardiac failure; registry:adverse_events

SF-36 physical component summary change (7 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	2.25 points	0.592		136	hypothetical; modified itt; registry:outcomes
40	A2	change	2.06 points	0.513		143	hypothetical; modified itt; registry:outcomes
40	A2 vs A1	md	-0.19 points		-1.63 to 1.26		hypothetical; modified itt; registry:outcomes
40	A3	change	2.21 points	0.574		137	hypothetical; modified itt; registry:outcomes
40	A3 vs A1	md	-0.04 points		-1.61 to 1.54		hypothetical; modified itt; registry:outcomes
40	A4	change	1.58 points	0.632		139	hypothetical; modified itt; registry:outcomes
40	A4 vs A1	md	-0.66 points		-2.25 to 0.92		hypothetical; modified itt; registry:outcomes

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	5 / 138	not stated; safety; registry:adverse_events
A2	events	8 / 143	not stated; safety; registry:adverse_events
A3	events	7 / 137	not stated; safety; registry:adverse_events
A4	events	4 / 141	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 138	not stated; randomized; registry:flow
A2	events	1 / 143	not stated; randomized; registry:flow
A3	events	0 / 137	not stated; randomized; registry:flow
A4	events	2 / 141	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	3 / 138	not stated; safety; registry:adverse_events
A2	events	18 / 143	not stated; safety; registry:adverse_events
A3	events	26 / 137	not stated; safety; registry:adverse_events
A4	events	24 / 141	not stated; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	2 / 138	not stated; safety; registry:adverse_events
A2	events	7 / 143	not stated; safety; registry:adverse_events
A3	events	9 / 137	not stated; safety; registry:adverse_events
A4	events	20 / 141	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	13 / 138	not stated; safety; registry:adverse_events
A2	events	27 / 143	not stated; safety; registry:adverse_events
A3	events	29 / 137	not stated; safety; registry:adverse_events
A4	events	36 / 141	not stated; safety; registry:adverse_events

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	5 / 138	not stated; safety; registry:adverse_events
A2	events	12 / 143	not stated; safety; registry:adverse_events
A3	events	23 / 137	not stated; safety; registry:adverse_events
A4	events	20 / 141	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (12 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 138	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	0 / 138	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events
A1	events	0 / 138	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	1 / 143	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events
A2	events	1 / 143	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	1 / 143	not stated; safety; cholecystitis acute; registry:adverse_events
A3	events	0 / 137	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events
A3	events	0 / 137	not stated; safety; cholecystitis acute; registry:adverse_events
A3	events	2 / 137	not stated; safety; cholelithiasis; registry:adverse_events
A4	events	0 / 141	not stated; safety; cholecystitis acute; registry:adverse_events
A4	events	0 / 141	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events
A4	events	0 / 141	not stated; safety; cholelithiasis; registry:adverse_events

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	21 / 138	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	21 / 143	not stated; safety; diabetic retinopathy; registry:adverse_events
A3	events	8 / 137	not stated; safety; diabetic retinopathy; registry:adverse_events
A4	events	24 / 141	not stated; safety; diabetic retinopathy; registry:adverse_events