The use of small molecule inhibitors of the enzyme dipeptidyl peptidase IV (DPP4i)
was proposed in 1998 as an approach to the management of diabetes, acting by reducing
glucagon-like peptide 1 (GLP-1) degradation and hence potentiating its insulinotropic
effect [
[1]
]. By 2005, effects of the DPP4i vildagliptin [
[2]
] and sitagliptin [
[3]
] were reported in human trials, leading to the development of a class of drugs whose
use among US Medicare beneficiaries alone accounted for expenditure of $1.5 billion
in 2012, increasing to $3.9 billion in 2017 [
- Herman G.A.
- Stevens C.
- Van Dyck K.
- Bergman A.
- Yi B.
- De Smet M.
- et al.
Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase
IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled
studies with single oral doses.
Clin Pharmacol Ther. 2005; 78: 675-688
[4]
]. During these two decades, there have been tremendous changes in our understanding
of the outcomes of treatment of type 2 diabetes (T2D), with questions raised about
potential harms of rosiglitazone by some authors [
- Sumarsono A.
- Everett B.M.
- McGuire D.K.
- Fonarow G.C.
- Butler J.
- Pandey A.
- et al.
Trends in aggregate use and associated expenditures of antihyperglycemic therapies
among US medicare beneficiaries between 2012 and 2017.
JAMA Intern Med. 2019; https://doi.org/10.1001/jamainternmed.2019.3884
[5]
], although debated [
[6]
], leading to an administrative decision by the US FDA that all treatments for T2D
are required to undergo clinical trials to determine whether they are safe in persons
with cardiovascular disease (CVD), considerably increasing the cost of developing
such treatment [
[7]
].To read this article in full you will need to make a payment
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References
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Article info
Publication history
Published online: October 30, 2019
Accepted:
October 23,
2019
Received:
October 6,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
