Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for
the treatment of type 2 diabetes.
Author(s): Mikhail N.
Affiliation(s): Endocrinology Division, Department of Medicine, Olive-View-UCLA Medical Center,
14445 Olive View Drive, Sylmar, CA 91342, USA. nmikhail@ladhs.org
Publication date & source: 2008, Expert Opin Investig Drugs. , 17(6):845-53
BACKGROUND: Exenatide is an incretin mimetic, while sitagliptin and vildagliptin
are incretin enhancers used as adjunctive therapy in patients with type 2
diabetes failing oral agents. Sitagliptin and vildagliptin can also be used as
monotherapy in patients with type 2 diabetes uncontrolled by diet.
OBJECTIVE: To provide a critical review of clinical trials of exenatide,
sitagliptin and vildagliptin.
METHOD: Review of Phase III clinical trials based on Medline search published up
to April 2008.
RESULTS: The use of exenatide is associated with reduction in average hemoglobin
A1c (HbA1c) levels of approximately 0.8% compared with baseline. The
corresponding reduction with either sitagliptin or vildagliptin is 0.7%. The
actions of incretin-based drugs predominantly target postprandial hyperglycemia.
Treatment-related hypoglycemia is generally mild, and mainly occurs when used
with sulfonylureas (SUs). Exenatide treatment leads to a mild weight loss of
around 2 kg after 30 weeks, whereas sitagliptin and vildagliptin have generally
neutral effect on weight. Sitagliptin and vildagliptin are well tolerated in
trials lasting up to 52 weeks. Meanwhile, 5 - 10% of patients cannot tolerate
exenatide due to adverse effects, mainly nausea and vomiting. The three drugs are
limited by the lack of long-term safety and efficacy data, as well as by their
high cost.
CONCLUSION: Exenatide, sitagliptin and vildagliptin are useful add-on therapy for
type 2 diabetes that is suboptimally controlled on oral agents, particularly when
there is concern about weight gain and hypoglycemia, or when postprandial
hyperglycemia is the major cause of inadequate glycemic control. Sitagliptin and
vildagliptin may be used as monotherapy in patients who cannot tolerate metformin
or SU, and sitagliptin may be used as alternative to metformin in renal
insufficiency.
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