Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes.

Cervera A, Wajcberg E, Sriwijitkamol A, Fernandez M, Zuo P, Triplitt C, Musi N, DeFronzo RA, Cersosimo E

American journal of physiology. Endocrinology and metabolism11 Mar 2008Cited by 118 (Europe PMC)

PMID18334612DOI10.1152/ajpendo.00030.2008PepBankPUB-18334612

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study11

6 results from studies that gave the peptide. 6 results from people.

01HumanNon-randomized trialMechanism
In subjects with type 2 diabetes, intravenous exenatide reduced post-meal hyperglycemia versus saline.
In plain wordsIn people with diabetes, intravenous exenatide lowered post-meal blood sugar compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreasePost-meal hyperglycemia
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · intravenous · 6 h post mealAs given in this study (human).
Measurements
Plasma glucose
138 mg/dl
exenatide
Plasma glucose
206 mg/dl
saline
Source sentences
Summary
Post-meal hyperglycemia was markedly reduced (P < 0.01) in EXE (138 +/- 16 mg/dl) and in E+G (165 +/- 12) compared with CON (206 +/- 15).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
Report a problemFND-1833461201
02HumanNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide decreased plasma glucagon by approximately 20% from baseline.
In plain wordsIn people with diabetes, exenatide reduced plasma glucagon compared with baseline.
Peptide
Exenatide (exendin-4)
Outcome
DecreasePlasma glucagon
Study
n = 12
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · intravenous · 6 h post mealAs given in this study (human).
Measurements
Glucagon reduction
≈ 20%
exenatide
Plasma glucagon
73 pg/ml
exenatide
Plasma glucagon
≈ 90 pg/ml
baseline
Source sentences
Summary
Baseline plasma glucagon ( approximately 90 pg/ml) decreased by approximately 20% to 73 +/- 4 pg/ml in EXE (P < 0.01) and was not different from CON in E+G (81 +/- 2).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
Report a problemFND-1833461203
03HumanNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide suppressed endogenous glucose production more than saline.
In plain wordsIn people with diabetes, exenatide suppressed the body's glucose production more than saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseEndogenous glucose production
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · intravenous · 6 h post mealAs given in this study (human).
Measurements
Suppression
54%
exenatide
Suppression
26%
saline
Endogenous glucose production before
231 mg/min
exenatide
Endogenous glucose production after
108 mg/min
exenatide
Endogenous glucose production before
254 mg/min
saline
Endogenous glucose production after
189 mg/min
saline
Source sentences
Summary
EGP was suppressed by exenatide [231 +/- 9 to 108 +/- 8 mg/min (54%) vs. 254 +/- 29 to189 +/- 27 mg/min (26%, P < 0.001, EXE vs. CON] and partially reversed by glucagon replacement [247 +/- 15 to 173 +/- 18 mg/min (31%)].
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
Report a problemFND-1833461205
04HumanNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide reduced oral glucose appearance versus saline.
In plain wordsIn people with diabetes, exenatide reduced oral glucose appearance compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseOral glucose appearance
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · intravenous · 6 h post mealAs given in this study (human).
Measurements
Oral glucose appearance
23 g
exenatide
Oral glucose appearance
39 g
saline
Source sentences
Summary
Oral glucose appearance was 39 +/- 4 g in CON vs. 23 +/- 6 g in EXE (P < 0.001) and 15 +/- 5 g in E+G, (P < 0.01 vs. CON).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
Report a problemFND-1833461207
05HumanNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide increased splanchnic glucose retention versus saline.
In plain wordsIn people with diabetes, exenatide increased glucose retained in the gut and liver region compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseSplanchnic glucose retention
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · intravenous · 6 h post mealAs given in this study (human).
Measurements
Retained glucose
≈ 52 g
exenatide
Retained glucose
≈ 36 g
saline
Source sentences
Summary
The glucose retained within the splanchnic bed increased from approximately 36g in CON to approximately 52g in EXE and to approximately 60g in E+G (P < 0.001 vs. CON).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
Report a problemFND-1833461209
06HumanNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide reduced acetaminophen AUC by approximately 80% versus saline.
In plain wordsIn people with diabetes, exenatide reduced acetaminophen exposure compared with saline, consistent with slower stomach emptying.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAcetaminophen AUC
Study
n = 12
Comparator
Intravenous saline
Outcome group
Gastrointestinal motility · Gastrointestinal
Studied dose
Dose not stated · intravenous · 6 h post mealAs given in this study (human).
Measurements
Acetaminophen AUC reduction
≈ 80%
exenatide versus saline
Source sentences
Summary
Acetaminophen((AUC)) was reduced by approximately 80% in EXE vs. CON (P < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
Acetaminophen was given with the mixed meal (75 g glucose, 25 g fat, 20 g protein) to monitor gastric emptying.
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
Report a problemFND-1833461211

Studies that did not test the peptide alone5

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

07HumanNot a test of Exenatide (exendin-4) aloneNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide plus glucagon reduced post-meal hyperglycemia versus saline.
In plain wordsIn people with diabetes, exenatide plus glucagon lowered post-meal blood sugar compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreasePost-meal hyperglycemia with glucagon
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Measurements
Plasma glucose
165 mg/dl
exenatide plus glucagon
Plasma glucose
206 mg/dl
saline
Source sentences
Summary
Post-meal hyperglycemia was markedly reduced (P < 0.01) in EXE (138 +/- 16 mg/dl) and in E+G (165 +/- 12) compared with CON (206 +/- 15).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-1833461202
08HumanNot a test of Exenatide (exendin-4) aloneNon-randomized trialMechanism
In subjects with type 2 diabetes, plasma glucagon with exenatide plus glucagon did not differ from saline.
In plain wordsIn people with diabetes, glucagon levels with exenatide plus glucagon were similar to saline.
Peptide
Exenatide (exendin-4)
Outcome
No significant changePlasma glucagon with replacement
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Measurements
Plasma glucagon
81 pg/ml
exenatide plus glucagon
Source sentences
Summary
Baseline plasma glucagon ( approximately 90 pg/ml) decreased by approximately 20% to 73 +/- 4 pg/ml in EXE (P < 0.01) and was not different from CON in E+G (81 +/- 2).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-1833461204
09HumanNot a test of Exenatide (exendin-4) aloneNon-randomized trialMechanism
In subjects with type 2 diabetes, glucagon replacement partially reversed exenatide suppression of endogenous glucose production.
In plain wordsIn people with diabetes, added glucagon partly reversed glucose-production suppression compared with exenatide alone.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseGlucagon reversal of glucose-production suppression
Study
n = 12
Comparator
Exenatide alone
Outcome group
Glycemic control · Metabolic and weight
Measurements
Suppression
31%
exenatide plus glucagon
Endogenous glucose production before
247 mg/min
exenatide plus glucagon
Endogenous glucose production after
173 mg/min
exenatide plus glucagon
Source sentences
Summary
EGP was suppressed by exenatide [231 +/- 9 to 108 +/- 8 mg/min (54%) vs. 254 +/- 29 to189 +/- 27 mg/min (26%, P < 0.001, EXE vs. CON] and partially reversed by glucagon replacement [247 +/- 15 to 173 +/- 18 mg/min (31%)].
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-1833461206
10HumanNot a test of Exenatide (exendin-4) aloneNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide plus glucagon reduced oral glucose appearance versus saline.
In plain wordsIn people with diabetes, exenatide plus glucagon reduced oral glucose appearance compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseOral glucose appearance with glucagon
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Measurements
Oral glucose appearance
15 g
exenatide plus glucagon
Oral glucose appearance
39 g
saline
Source sentences
Summary
Oral glucose appearance was 39 +/- 4 g in CON vs. 23 +/- 6 g in EXE (P < 0.001) and 15 +/- 5 g in E+G, (P < 0.01 vs. CON).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-1833461208
11HumanNot a test of Exenatide (exendin-4) aloneNon-randomized trialMechanism
In subjects with type 2 diabetes, exenatide plus glucagon increased splanchnic glucose retention versus saline.
In plain wordsIn people with diabetes, exenatide plus glucagon increased glucose retention in the gut and liver region compared with saline.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseSplanchnic glucose retention with glucagon
Study
n = 12
Comparator
Intravenous saline
Outcome group
Glycemic control · Metabolic and weight
Measurements
Retained glucose
≈ 60 g
exenatide plus glucagon
Retained glucose
≈ 36 g
saline
Source sentences
Summary
The glucose retained within the splanchnic bed increased from approximately 36g in CON to approximately 52g in EXE and to approximately 60g in E+G (P < 0.001 vs. CON).
1 context sentence(design, population, supporting numbers)
Summary · context
Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G).
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Report a problemFND-1833461210

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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

Subjects

Terms as the source lists them.

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