AMPLITUDE-D

TerminatedPhase 3Results posted

Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

A 56-week, Multicenter, Open-label, Active-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly Compared to Dulaglutide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

Lead sponsor

Sanofi

Assets

Dulaglutide / Efpeglenatide

Listed sites

Recruiting sites

—

Enrollment

908

actual

Study population

Type 2 diabetes

Key I/E criterion

—

Primary endpoint

•HbA1c, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03684642

Org study IDEFC14829

Secondary ID2017-002956-10

Secondary IDU1111-1205-3150UTN

Timeline

Milestones

Study first posted2018-09-26actual

Study start2018-09-26actual

Primary completion2020-10-13actual

Study completion2020-11-17actual

Last update posted2021-11-01actual

Results first posted2021-11-01actual

Assets

Investigational agents

Dulaglutide Efpeglenatide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Participant must be greater than or equal to (>=) 18 years of age at the time of signing the informed consent.

•Participants with T2DM.

•Diabetes diagnosed at least 1 year before screening.

•Participants on stable dose of at least 1500 milligram per day (mg/day) of metformin, or tolerated maximum dose, or as per country regulation if less, for at least 3 months prior to screening.

•HbA1c between 7.0 percent (%) and 10.0% (inclusive) measured by the central laboratory at screening.

Exclusion criteria

•Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months prior to screening) or planned: intravitreal injections or laser or vitrectomy surgery.

•Clinically relevant history of gastrointestinal (GI) disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and not controlled gastroesophageal reflux disease requiring medical treatment within 6 months prior to screening or history of surgery affecting gastric emptying.

•History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy had been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy.

•Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC (e.g., multiple endocrine neoplasia syndromes).

•Body weight change of greater than or equal to (>=) 5 kilogram within the last 3 months prior to screening.

•Systolic blood pressure greater than (>)180 millimeter of mercury (mmHg) and/or diastolic blood pressure >100 mmHg at randomization.

•Severe renal disease as defined by estimated glomerular filtration rate (eGFR), by Modification of Diet in Renal Disease (MDRD)] of less than (<)30 mL/min/1.73 m^2.

•Laboratory findings at the screening visit:

•Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 * upper limit of normal (ULN) or total bilirubin >1.5 * ULN (except in case of documented Gilbert's syndrome);

•Amylase and/or lipase: >3 * ULN;

•Calcitonin >=5.9 picomoles per liter (pmol/L) (20 picograms per milliliter).

•Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to screening, or planned during study period.

•Pregnant (confirmed by serum pregnancy test at screening) or breast-feeding women.

•Women of childbearing potential (WOCBP) not willing to use highly effective method(s) of birth control or who are unwilling to be tested for pregnancy during the study period and for at least 5 weeks after the last dose of study intervention.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Safety / tolerability / PK

Weight & body composition

2 endpoints

Secondary/registry result

Change From Baseline to Week 56 in Body Weight

Time frame:Baseline to Week 56

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), kilogram	95% CI
Efpeglenatide 4 mg	-2.87	—
Efpeglenatide 6 mg	-3.04	—
Dulaglutide 1.5 mg	-2.81	—

Secondary/protocol endpoint

Change From Baseline to Week 56 in Body Weight

Time frame:Baseline to Week 56

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

6 endpoints

Primary/registry result

Change From Baseline to Week 56 in HbA1c

Time frame:Baseline to Week 56

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), percentage of HbA1c	95% CI
Efpeglenatide 4 mg	-1.12	—
Efpeglenatide 6 mg	-1.17	—
Dulaglutide 1.5 mg	-1.09	—

Least Square (LS) Mean difference-0.0395% CI-0.20 – 0.14

LS Mean Difference-0.0895% CI-0.25 – 0.09

p0.7064ANCOVA

p0.3427ANCOVA

Primary/protocol endpoint

Change From Baseline to Week 56 in HbA1c

Time frame:Baseline to Week 56

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Number of Participants With HbA1c < 7.0 %

Time frame:Week 56

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Efpeglenatide 4 mg	155	—
Efpeglenatide 6 mg	157	—
Dulaglutide 1.5 mg	150	—

Secondary/registry result

Change From Baseline to Week 56 in Fasting Plasma Glucose (FPG)

Time frame:Baseline to Week 56

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), millimoles per liter (mmol/L)	95% CI
Efpeglenatide 4 mg	-1.81	—
Efpeglenatide 6 mg	-1.57	—
Dulaglutide 1.5 mg	-1.71	—

Secondary/protocol endpoint

Number of Participants With HbA1c < 7.0 %

Time frame:Week 56

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change From Baseline to Week 56 in Fasting Plasma Glucose (FPG)

Time frame:Baseline to Week 56

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Safety / tolerability / PK

4 endpoints

Secondary/registry result

Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], Severe Hypoglycemia)

Time frame:Baseline up to Week 56

Documented hypoglycemia

threshold achievement, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Posted result

Group	Value (count_of_participants), Participants	95% CI
Efpeglenatide 4 mgDocumented symptomatic hypoglycemia (<54 mg/dL)	3	—
Severe hypoglycemia	0	—
Efpeglenatide 6 mgDocumented symptomatic hypoglycemia (<54 mg/dL)	1	—
Severe hypoglycemia	0	—
Dulaglutide 1.5 mgDocumented symptomatic hypoglycemia (<54 mg/dL)	0	—
Severe hypoglycemia	0	—

Secondary/registry result

Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year

Time frame:Baseline up to Week 56

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Posted result

Group	Value (number), events per participant-year	95% CI
Efpeglenatide 4 mgDocumented symptomatic hypoglycemia (<54 mg/dL)	0.01	—
Severe hypoglycemia	0	—
Efpeglenatide 6 mgDocumented symptomatic hypoglycemia (<54 mg/dL)	0.01	—
Severe hypoglycemia	0	—
Dulaglutide 1.5 mgDocumented symptomatic hypoglycemia (<54 mg/dL)	0	—
Severe hypoglycemia	0	—

Secondary/protocol endpoint

Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], Severe Hypoglycemia)

Time frame:Baseline up to Week 56

Documented hypoglycemia

threshold achievement, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Secondary/protocol endpoint

Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year

Time frame:Baseline up to Week 56

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes: The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials.
Diabetes, obesity & metabolism2023 Aug (month)PMID37013892doi:10.1111/dom.15079via pubmed acronym asset candidate

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.