Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake

A randomized, cross-over study

Ralph A Defronzo, Ted Okerson, Prabhakar Viswanathan, Xuesong Guan, John H. Holcombe, Leigh MacConell

Research output: Contribution to journalArticle

311 Citations (Scopus)

Abstract

Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients. Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33 ± 5 kg/m2; HbA1c: 8.5 ± 1.2%; 2-h PPG: 245 ± 65 mg/dL. Patients received exenatide (5 μg BID for 1 week, then 10 μg BID for 1 week) or sitagliptin (100 mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581). Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133 ± 6 mg/dL versus 208 ± 6 mg/dL, p < 0.0001 (evaluable, N= 61). Switching from exenatide to sitagliptin increased 2-h PPG by +73 ± 11 mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by - 76 ± 10 mg/dL. Postprandial glucose parameters (AUC, Cave, Cmax) were lower with exenatide than sitagliptin (p<0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (-15 ± 4 mg/dL vs. -19 ± 4 mg/dL, p=0,3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50 ± 0.26, p=0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88 ± 0.03, p=0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90 ± 0.04, p=0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56 ± 0.05, p<0.0001). Exenatide reduced total caloric intake compared to sitagliptin (-134 ± 97 kcal vs. +130 ± 97 kcal, p=0.0227, N= 25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature. Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.

Original languageEnglish (US)
Pages (from-to)2943-2952
Number of pages10
JournalCurrent Medical Research and Opinion
Volume24
Issue number10
DOIs
StatePublished - Oct 2008

Fingerprint

Gastric Emptying
Energy Intake
Glucagon
Cross-Over Studies
Insulin
Glucose
Area Under Curve
Sitagliptin Phosphate
exenatide
Acetaminophen
Meals
Incretins
Metformin
Therapeutics
Double-Blind Method
Registries

Keywords

  • DPP-4 inhibitor
  • Exenatide
  • GLP-1
  • Glycemia
  • Incretin mimetic
  • Postprandial glucose
  • Sitagliptin
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake : A randomized, cross-over study. / Defronzo, Ralph A; Okerson, Ted; Viswanathan, Prabhakar; Guan, Xuesong; Holcombe, John H.; MacConell, Leigh.

In: Current Medical Research and Opinion, Vol. 24, No. 10, 10.2008, p. 2943-2952.

Research output: Contribution to journalArticle

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abstract = "Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients. Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54{\%} female; BMI: 33 ± 5 kg/m2; HbA1c: 8.5 ± 1.2{\%}; 2-h PPG: 245 ± 65 mg/dL. Patients received exenatide (5 μg BID for 1 week, then 10 μg BID for 1 week) or sitagliptin (100 mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581). Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133 ± 6 mg/dL versus 208 ± 6 mg/dL, p < 0.0001 (evaluable, N= 61). Switching from exenatide to sitagliptin increased 2-h PPG by +73 ± 11 mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by - 76 ± 10 mg/dL. Postprandial glucose parameters (AUC, Cave, Cmax) were lower with exenatide than sitagliptin (p<0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (-15 ± 4 mg/dL vs. -19 ± 4 mg/dL, p=0,3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50 ± 0.26, p=0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88 ± 0.03, p=0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90 ± 0.04, p=0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56 ± 0.05, p<0.0001). Exenatide reduced total caloric intake compared to sitagliptin (-134 ± 97 kcal vs. +130 ± 97 kcal, p=0.0227, N= 25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature. Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.",
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TY - JOUR

T1 - Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake

T2 - A randomized, cross-over study

AU - Defronzo, Ralph A

AU - Okerson, Ted

AU - Viswanathan, Prabhakar

AU - Guan, Xuesong

AU - Holcombe, John H.

AU - MacConell, Leigh

PY - 2008/10

Y1 - 2008/10

N2 - Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients. Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33 ± 5 kg/m2; HbA1c: 8.5 ± 1.2%; 2-h PPG: 245 ± 65 mg/dL. Patients received exenatide (5 μg BID for 1 week, then 10 μg BID for 1 week) or sitagliptin (100 mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581). Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133 ± 6 mg/dL versus 208 ± 6 mg/dL, p < 0.0001 (evaluable, N= 61). Switching from exenatide to sitagliptin increased 2-h PPG by +73 ± 11 mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by - 76 ± 10 mg/dL. Postprandial glucose parameters (AUC, Cave, Cmax) were lower with exenatide than sitagliptin (p<0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (-15 ± 4 mg/dL vs. -19 ± 4 mg/dL, p=0,3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50 ± 0.26, p=0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88 ± 0.03, p=0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90 ± 0.04, p=0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56 ± 0.05, p<0.0001). Exenatide reduced total caloric intake compared to sitagliptin (-134 ± 97 kcal vs. +130 ± 97 kcal, p=0.0227, N= 25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature. Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.

AB - Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients. Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33 ± 5 kg/m2; HbA1c: 8.5 ± 1.2%; 2-h PPG: 245 ± 65 mg/dL. Patients received exenatide (5 μg BID for 1 week, then 10 μg BID for 1 week) or sitagliptin (100 mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581). Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133 ± 6 mg/dL versus 208 ± 6 mg/dL, p < 0.0001 (evaluable, N= 61). Switching from exenatide to sitagliptin increased 2-h PPG by +73 ± 11 mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by - 76 ± 10 mg/dL. Postprandial glucose parameters (AUC, Cave, Cmax) were lower with exenatide than sitagliptin (p<0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (-15 ± 4 mg/dL vs. -19 ± 4 mg/dL, p=0,3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50 ± 0.26, p=0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88 ± 0.03, p=0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90 ± 0.04, p=0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56 ± 0.05, p<0.0001). Exenatide reduced total caloric intake compared to sitagliptin (-134 ± 97 kcal vs. +130 ± 97 kcal, p=0.0227, N= 25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature. Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.

KW - DPP-4 inhibitor

KW - Exenatide

KW - GLP-1

KW - Glycemia

KW - Incretin mimetic

KW - Postprandial glucose

KW - Sitagliptin

KW - Type 2 diabetes

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