Effects of exenatide versus sitagliptin on postprandial glucose, insulin and
glucagon secretion, gastric emptying, and caloric intake: a randomized,
cross-over study.
Author(s): DeFronzo RA, Okerson T, Viswanathan P, Guan X, Holcombe JH, MacConell L.
Affiliation(s): University of Texas Health Science Center, Department of Medicine, Diabetes
Division (MSC 7886), 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
albarado@uthscsa.edu
Publication date & source: 2008, Curr Med Res Opin. , 24(10):2943-52
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/m(2);
HbA(1c): 8.5 +/- 1.2%; 2-h PPG: 245 +/- 65 mg/dL. Patients received exenatide (5
microg BID for 1 week, then 10 microg 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, C(ave), C(max)) 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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