Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus
Abstract
Dipeptidyl peptidase 4 inhibitors (DPP4i) have been available for treating type 2 diabetes mellitus since 2006. Although they are a diverse group, DPP4i are all small, orally available molecules that interact with the catalytic site of DPP4 without disturbing any of its other known functions, including its effects on the immune system. DPP4i have no intrinsic glucose-lowering activity, so their efficacy as anti-diabetic agents is related directly to their ability to inhibit DPP4 activity and is mediated through the effects of the substrates they protect. Of these, the incretin hormone, glucagon-like peptide 1, is probably the most important. As the effects of glucagon-like peptide 1 are glucose-dependent, the risk of hypoglycaemia with DPP4i is low. Class effects, which are directly related to the mechanism of action, are common to all DPP4i; these include their overall good safety profile and tolerability, as well as their efficacy in improving glycaemic control, but also, potentially, a small increased risk of acute pancreatitis. Compound-specific effects are those related to their differing chemistries and/or pharmacokinetic profiles. These compound-specific effects could affect the way in which individual DPP4i are used therapeutically and potentially explain off-target adverse effects, such as hospitalization for heart failure, which is seen only with one DPP4i. Overall, DPP4i have a favourable therapeutic profile and are safe and effective in the majority of patients wi…
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For type 2 diabetes, complementary disease-modifying therapies may reduce or eliminate the need for insulin administration.
“For type 2 diabetes, complementary disease-modifying therapies that may reduce or eliminate the need for insulin administration have also represented a rapidly expanding field of interest130–132.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [130]
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100 years of insulin: celebrating the past, present and future of diabetes therapy
Sims, E. K., Carr, A. L. J., Oram, R. A., DiMeglio, L. A., & Evans-Molina, C. (2021) · Nature Medicine · doi:10.1038/s41591-021-01418-2 · Cited by 270 · see citing works
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- Authors
- Deacon, C. F.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Deacon, Carolyn F.
- ORCID
- Deacon, Carolyn F.
- Venue
- Nature Reviews Endocrinology
- Published
- 2020-09-14
- Volume
- 16
- Issue
- 11
- Pages
- 642-653
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W3086213814
- Cited by
- 398
- References
- 10
- Citations by year
- 2026: 59 · 2025: 77 · 2024: 95 · 2023: 68 · 2022: 67 · 2021: 30 · 2020: 2
- FWCI
- 6.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- DPP-4 inhibitors, type 2 diabetes, glucagon-like peptide-1, incretins, glucose-dependent insulin secretion, hypoglycemia, acute pancreatitis, heart failure hospitalization, drug safety, glycemic control, pharmacokinetics
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Dipeptidyl-Peptidase IV Inhibitors
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