Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

Davis TME, Giczewska A, Lokhnygina Y, Mentz RJ, Sattar N, Holman RR

Cardiovascular diabetology27 Jun 2022Cited by 5 (Europe PMC)

PMID35761271PMCIDPMC9238154DOI10.1186/s12933-022-01555-zPepBankPUB-35761271

Summary

BackgroundTo determine whether there were racial differences in short-term cardiometabolic responses to once-weekly exenatide (EQW) in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).MethodsEXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo. Background glucose-lowering/other cardiovascular therapies were unaltered for 6 months post-randomization unless clinically essential, facilitating comparison of EQW-associated effects in 14,665 evaluable participants self-identifying as White (n = 11,113), Asian (n = 1444), Black (n = 870), or Other Race (n = 1,238. Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.ResultsMean 6-month placebo-adjusted HbA_1c reductions were similar in the four groups (range 0.54-0.67% [5.9 to 7.3 mmol/mol], P = 0.11 for race×treatment interaction), with no significant difference in Asians (reference) versus other groups after covariate adjustment (all P ≥ 0.10). Six-month placebo-adjusted mean changes in systolic (-1.8 to 0.0 mmHg) and diastolic (0.2 to 1.2 mmHg) blood pressure, serum LDL (- 0.06 to 0.02 mmol/L) and HDL (0.00 to 0.01 mmol/L) cholesterol, and serum triglycerides (-0.1 to 0.0 mmol/L) were similar in the racial groups (P ≥ 0.19 for race×treatment interaction and all P ≥ 0.13 for comparisons of Asians with other races). Resting pulse rate increased more in Asians (4 beats/min) than in other groups (≤ 3 beats/min, P = 0.016 for race×treatment interaction and all P ≤ 0.050 for comparisons of Asians with other races).ConclusionsShort-term cardiometabolic responses to EQW were similar in the main racial groups in EXSCEL, apart from a greater pulse rate increase in Asians.Trial registrationhttps://clinicaltrials.gov NCT01144338.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In patients with T2D, exenatide reduced HbA1c versus placebo similarly across racial groups.
In plain wordsExenatide lowered average blood sugar versus placebo similarly across racial groups.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseHbA1c across races
Study
n = 14,665
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Placebo-adjusted HbA1c reduction
0.54 to 0.67%
racial group range
Source sentences
Summary
Mean 6-month placebo-adjusted HbA_1c reductions were similar in the four groups (range 0.54-0.67% [5.9 to 7.3 mmol/mol], P = 0.11 for race×treatment interaction), with no significant difference in Asians (reference) versus other groups after covariate adjustment (all P ≥ 0.10).
2 context sentences(design, population, supporting numbers)
Summary · context
EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo.
Summary · context
Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.
Show in the study text Report a problemFND-3576127101
02HumanRandomized controlled trialEfficacy outcome
In patients with T2D, placebo-adjusted systolic pressure changes with exenatide were similar across racial groups.
In plain wordsExenatide's systolic blood pressure changes compared with placebo were similar across racial groups.
Peptide
Exenatide (exendin-4)
Outcome
Direction not reportedSystolic blood pressure across races
Study
n = 14,665
Comparator
Placebo
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Systolic blood pressure change
−1.8 to 0 mmHg
placebo-adjusted racial group range
Source sentences
Summary
Six-month placebo-adjusted mean changes in systolic (-1.8 to 0.0 mmHg) and diastolic (0.2 to 1.2 mmHg) blood pressure,
3 context sentences(design, population, supporting numbers)
Summary · context
were similar in the racial groups (P ≥ 0.19 for race×treatment interaction and all P ≥ 0.13 for comparisons of Asians with other races).
Summary · context
EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo.
Summary · context
Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.
Show in the study text Report a problemFND-3576127102
03HumanRandomized controlled trialEfficacy outcome
In patients with T2D, placebo-adjusted diastolic pressure changes with exenatide were similar across racial groups.
In plain wordsExenatide's diastolic blood pressure changes compared with placebo were similar across racial groups.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseDiastolic blood pressure across races
Study
n = 14,665
Comparator
Placebo
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Diastolic blood pressure change
0.2 to 1.2 mmHg
placebo-adjusted racial group range
Source sentences
Summary
Six-month placebo-adjusted mean changes in systolic (-1.8 to 0.0 mmHg) and diastolic (0.2 to 1.2 mmHg) blood pressure,
3 context sentences(design, population, supporting numbers)
Summary · context
were similar in the racial groups (P ≥ 0.19 for race×treatment interaction and all P ≥ 0.13 for comparisons of Asians with other races).
Summary · context
EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo.
Summary · context
Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.
Show in the study text Report a problemFND-3576127103
04HumanRandomized controlled trialEfficacy outcome
In patients with T2D, placebo-adjusted LDL changes with exenatide were similar across racial groups.
In plain wordsExenatide's LDL cholesterol changes compared with placebo were similar across racial groups.
Peptide
Exenatide (exendin-4)
Outcome
MixedLDL cholesterol across races
Study
n = 14,665
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
LDL cholesterol change
−0.06 to 0.02 mmol/L
placebo-adjusted racial group range
Source sentences
Summary
serum LDL (- 0.06 to 0.02 mmol/L) and HDL (0.00 to 0.01 mmol/L) cholesterol, and serum triglycerides (-0.1 to 0.0 mmol/L) were similar in the racial groups
2 context sentences(design, population, supporting numbers)
Summary · context
EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo.
Summary · context
Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.
Show in the study text Report a problemFND-3576127104
05HumanRandomized controlled trialEfficacy outcome
In patients with T2D, placebo-adjusted HDL changes with exenatide were similar across racial groups.
In plain wordsExenatide's HDL cholesterol changes compared with placebo were similar across racial groups.
Peptide
Exenatide (exendin-4)
Outcome
Direction not reportedHDL cholesterol across races
Study
n = 14,665
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
HDL change
0 to 0.01 mmol/L
placebo-adjusted racial group range
Source sentences
Summary
serum LDL (- 0.06 to 0.02 mmol/L) and HDL (0.00 to 0.01 mmol/L) cholesterol, and serum triglycerides (-0.1 to 0.0 mmol/L) were similar in the racial groups
2 context sentences(design, population, supporting numbers)
Summary · context
EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo.
Summary · context
Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.
Show in the study text Report a problemFND-3576127105
06HumanRandomized controlled trialEfficacy outcome
In patients with T2D, placebo-adjusted triglyceride changes with exenatide were similar across racial groups.
In plain wordsExenatide's triglyceride changes compared with placebo were similar across racial groups.
Peptide
Exenatide (exendin-4)
Outcome
Direction not reportedTriglycerides across races
Study
n = 14,665
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Triglyceride change
−0.1 to 0 mmol/L
placebo-adjusted racial group range
Source sentences
Summary
serum LDL (- 0.06 to 0.02 mmol/L) and HDL (0.00 to 0.01 mmol/L) cholesterol, and serum triglycerides (-0.1 to 0.0 mmol/L) were similar in the racial groups
2 context sentences(design, population, supporting numbers)
Summary · context
EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo.
Summary · context
Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.
Show in the study text Report a problemFND-3576127106
07HumanRandomized controlled trialSafety outcome
In patients with T2D, exenatide-associated resting pulse increases were greater in Asians than in other racial groups.
In plain wordsExenatide increased resting pulse more in Asian patients than in other racial groups.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseResting pulse racial interaction
Study
n = 14,665
Comparator
Other racial groups
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Pulse increase
4 beats/min
Asians
Pulse increase
≤ 3 beats/min
other groups
Source sentences
Summary
Resting pulse rate increased more in Asians (4 beats/min) than in other groups (≤ 3 beats/min, P = 0.016 for race×treatment interaction and all P ≤ 0.050 for comparisons of Asians with other races).
2 context sentences(design, population, supporting numbers)
Summary · context
EXSCEL enrolled 14,752 patients with type 2 diabetes (hemoglobin A_1c (HbA_1c) 6.5-10.0% [48-86 mmol/mol]) with or without cardiovascular disease who were randomized double-blind to EQW or placebo.
Summary · context
Placebo-adjusted 6 month absolute changes in cardiometabolic variables were assessed using generalized linear models.
Show in the study text Report a problemFND-3576127107

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT01144338

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

AstraZenecan = 14,75218 Jun 2010 to 24 Apr 2017

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 8 Aug 2018

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

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