NCT01144338

Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus

Completed Phase 3 Results posted Last updated 8 August 2018

What this trial tests

Phase 3 trial testing Exenatide Once Weekly in Type 2 Diabetes Mellitus in 14,752 participants. Completed in 24 April 2017.

Timeline

18 June 2010

Primary endpoint
21 April 2017

24 April 2017

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	14,752
Start date	18 June 2010
Primary completion	21 April 2017
Estimated completion	24 April 2017
Sites	629 locations across Hong Kong, Colombia, Italy, Malaysia, Taiwan, Poland, South Korea, Philippines

Drugs / interventions tested

• Exenatide Once Weekly — full drug profile →
• Placebo

Conditions studied

• Type 2 Diabetes Mellitus — all drugs for Type 2 Diabetes Mellitus →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Type 2 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Primary Efficacy Outcome MACE Events Primary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

The primary efficacy outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke. The number of participants who had an event is reported in the results. The primary efficacy endpoint is the same as the primary safety endpoint, and the statistical analysis tests the superiority of exenatide against the placebo.

Group	Value	95% CI
Placebo	905
Exenatide Once Weekly	839

Primary Safety Outcome MACE Events Primary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

The primary safety outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke. The number of participants who had an event is reported in the results. The primary safety endpoint is the same as the primary efficacy endpoints, and the statistical analysis tests the non-inferiority of exenatide against placebo.

Group	Value	95% CI
Placebo	905
Exenatide Once Weekly	839

Secondary Efficacy Outcome All-Cause Mortality Secondary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

The secondary efficacy outcome variable is defined as the all-cause mortality (deaths). The number of participants who had an event is reported in the results.

Group	Value	95% CI
Placebo	584
Exenatide Once Weekly	507

Secondary Efficacy Outcome CV Death Secondary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

Component of the primary efficacy outcome: cardiovascular death. The number of participants who had an event is reported in the results.

Group	Value	95% CI
Placebo	383
Exenatide Once Weekly	340

Secondary Efficacy Outcome MI Secondary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

Component of primary efficacy outcome: fatal or non-fatal MI. The number of participants who had an event is reported in the results.

Group	Value	95% CI
Placebo	493
Exenatide Once Weekly	483

Secondary Efficacy Outcome Stroke Secondary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

Component of primary efficacy outcome: fatal or non-fatal stroke. The number of participants who had an event is reported in the results.

Group	Value	95% CI
Placebo	218
Exenatide Once Weekly	187

Secondary Efficacy Outcome Hospitalization for ACS Secondary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

The secondary efficacy outcome variable is defined as hospitalization for acute coronary syndrome. The number of participants who had an event is reported in the results.

Group	Value	95% CI
Placebo	570
Exenatide Once Weekly	602

Secondary Efficacy Outcome Hospitalization for HF Secondary · Time to first event. Information collected during study period (anticipated to be up to 7.5 years).

The secondary efficacy outcome variable is defined as hospitalization for heart failure. The number of participants who had an event is reported in the results.

Group	Value	95% CI
Placebo	231
Exenatide Once Weekly	219

Adverse events — posted to ClinicalTrials.gov

Time frame: During study period up to 7.5 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1222/7372 (17%)

Deaths: 584/7372

Exenatide Once Weekly

Serious: 1234/7344 (17%)

Deaths: 507/7344

Serious adverse events (861 terms)

Reaction	System	Placebo	Exenatide Once Weekly
Non-cardiac chest pain	General disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Pancreatitis	Gastrointestinal disorders	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	—	—
Breast cancer female	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Nephrolithiasis	Renal and urinary disorders	—	—
Umbilical hernia	Gastrointestinal disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Depression	Psychiatric disorders	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: Non-cardiac chest pain, Osteoarthritis, Chronic obstructive pulmonary disease, Pancreatitis, Gastrointestinal haemorrhage, Anaemia, Prostate cancer, Basal cell carcinoma.

Data from ClinicalTrials.gov NCT01144338 adverse events section.

Sponsor's own description

This study will compare the impact of including exenatide once weekly in addition to usual care vs. usual care without exenatide on major cardiovascular outcomes as measured by the primary composite endpoint of cardiovascular-related death, nonfatal myocardial infarction (MI), or nonfatal stroke.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.
   Holman RR, Bethel MA, Mentz RJ, Thompson VP, et al · · 2017 · cited 1491× · PMID 28910237 · DOI 10.1056/nejmoa1612917
2. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.
   Kahn SE, Cooper ME, Del Prato S. · · 2014 · cited 1100× · PMID 24315620 · DOI 10.1016/s0140-6736(13)62154-6
3. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations.
   Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. · · 2016 · cited 782× · PMID 27297342 · DOI 10.1161/circulationaha.116.022194
4. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction.
   Mentz RJ, Kelly JP, von Lueder TG, Voors AA, et al · · 2014 · cited 404× · PMID 25456761 · DOI 10.1016/j.jacc.2014.08.036
5. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.
   Li Y, Liu Y, Liu S, Gao M, et al · · 2023 · cited 392× · PMID 37037849 · DOI 10.1038/s41392-023-01400-z
6. Glucagon-Like Peptide 1 Receptor Agonists for Type 2 Diabetes.
   Hinnen D. · · 2017 · cited 262× · PMID 28848315 · DOI 10.2337/ds16-0026
7. Macrophage functions in lean and obese adipose tissue.
   Thomas D, Apovian C. · · 2017 · cited 231× · PMID 28641779 · DOI 10.1016/j.metabol.2017.04.005
8. Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists.
   Madsbad S. · · 2016 · cited 214× · PMID 26511102 · DOI 10.1111/dom.12596