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Cited by 34Diabetes Treatment and ManagementPharmacology and Obesity TreatmentPeptidase Inhibition and Analysis

Pharmacology of dipeptidyl peptidase-4 inhibitors and its use in the management of metabolic syndrome: a comprehensive review on drug repositioning

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Rameshrad, Maryam, Razavi, Bibi Marjan, Ferns, Gordon A. A., Hosseinzadeh, Hossein·2019·DARU Journal of Pharmaceutical Sciences
DOI 10.1007/s40199-019-00238-7PMC PMC6593018
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Abstract

Objectives Despite advances in our understanding of metabolic syndrome (MetS) and the treatment of each of its components separately, currently there is no single therapy approved to manage it as a single condition. Since multi-drug treatment increases drug interactions, decreases patient compliance and increases health costs, it is important to introduce single therapies that improve all of the MetS components. Evidence acquisition We conducted a PubMed, Scopus, Google Scholar, Web of Science, US FDA, utdo.ir and clinicaltrial.gov search, gathered the most relevant preclinical and clinical studies that have been published since 2010, and discussed the beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors to prevent and treat different constituent of the MetS as a single therapy. Furthermore, the pharmacology of DPP-4 inhibitors, focusing on pharmacodynamics, pharmacokinetics, drug interactions and their side effects are also reviewed. Results DPP-4 inhibitors or gliptins are a new class of oral anti-diabetic drugs that seem safe drugs with no severe side effects, commonly GI disturbance, infection and inflammatory bowel disease. They increase mass and function of pancreatic β-cells, and insulin sensitivity in liver, muscle and adipose tissue. It has been noted that gliptin therapy decreases dyslipidemia. DPP-4 inhibitors increase fatty oxidation, and cholesterol efflux, and decrease hepatic triglyceride synthase and de novo lipogenesis. They delay gastric emptying time and lead to satiety. Besides, gliptin therapy has anti-inflammatory and anti-atherogenic impacts, and improves endothelial function and reduces vascular stiffness. Conclusion The gathered data prove the efficacy of DPP-4 inhibitors in managing MetS in some levels beyond anti-diabetic effects. This review could be a lead for designing new DPP-4 inhibitors with greatest effects on MetS in future. Introducing drugs with polypharmacologic effects could increase the patient's compliance and decrease the health cost that there is not in multi-drug therapy. Graphical abstract ᅟ.

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  • DPP-4 inhibitors increase the mass and function of pancreatic β-cells, increase insulin sensitivity in liver, muscle, and adipose tissue, decrease dyslipidaemias, increase fat oxidation and cholesterol efflux, lower hepatic triglyceride synthase, decline de novo lipogenesis, postpone stomach emptying, promote satiety, have anti-inflammatory and antiatherogenic impacts, improve endothelial function

    “Their mechanism of action includes: increasing the mass and function of pancreatic β-cells; increasing insulin sensitivity in liver, muscle, and adipose tissue; decreasing dyslipidaemias; increasing fat oxidation and cholesterol efflux; lowering hepatic triglyceride synthase, decline de novo lipogenesis; postponing the time for stomach emptying and promoting satiety, have anti-inflammatory and ant”

    From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [69]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • DPP-4 inhibitors progressively replace sulfonylureas to manage type 2 diabetes mellitus in numerous countries.

    “DPP-4 Inhibitors, also known as “gliptins” like sitaglibtin, saxagliptin, linagliptin, and alogliptin, progressively replace sulfonylureas to manage T2DM in numerous countries.”

    From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [69]

    The Clinical studies section (page unavailable) reports that switching from glimepiride to sitagliptin reduced hypoglycemia risk in patients with type 2 diabetes. That supports use of a DPP-4 inhibitor in place of a sulfonylurea in a specific setting, but the paper does not establish a progressive replacement trend across numerous countries. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • DPP-4 inhibitors are not associated with hypoglycemia or weight gain, have a good safety profile, and are used as an alternative to drugs such as metformin and sulfonylureas when those fail.

    “The three main advantages of these drugs are: 1) not associated with hypoglycemia or weight gain; 2) have a good safety profile; and; 3) used as an alternative to drugs such as metformin and sulfonylureas when fail.”

    From A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. (2024) · cites this paper as [69]

    The Pharmacology of DPP-4 inhibitors section (page unavailable) reports a low incidence of hypoglycemia and lack of weight gain, while Side effects calls the drugs generally safe. Clinical studies describes a DPP-4 inhibitor as second-line therapy with metformin or as a replacement for a sulfonylurea, but does not say it is used when both metformin and sulfonylureas fail. Drug interactions also reports increased hypoglycemia risk when DPP-4 inhibitors are combined with sulfonylureas or insulin, so the unqualified claim of no association overstates the source. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Rameshrad, M., Razavi, B. M., Ferns, G. A. A., & Hosseinzadeh, H.
Affiliations
  • Mashhad University of Medical Sciences (IR)
  • Brighton and Sussex Medical School (GB)
Corresponding author
Hosseinzadeh, Hossein
ORCID
Venue
DARU Journal of Pharmaceutical Sciences
Publisher
Springer Science and Business Media LLC
Published
2019-01-23
Volume
27
Issue
1
Pages
341-360
ISSN
  • 1560-8115 (ISSN-L)
  • 2008-2231
DOI
10.1007/s40199-019-00238-7
PMC
PMC6593018
OpenAlex
W2913897873
Cited by
34
References
6
Citations by year
2026: 1 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 10 · 2020: 5
FWCI
0.69
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • DARU Journal of Pharmaceutical Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Mashhad University of Medical Sciences
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
Keywords
DPP-4 inhibitors, metabolic syndrome, drug repurposing, pharmacokinetics, pharmacodynamics, drug interactions, dyslipidemia, hepatic lipogenesis, insulin sensitivity, beta-cell function, satiety, endothelial function, anti-inflammatory activity, antiatherogenic effects
MeSH terms
Drug Interactions, Humans, Patient Compliance, Metabolic Syndrome, Lipogenesis, Insulin-Secreting Cells, Dipeptidyl-Peptidase IV Inhibitors, Drug Repositioning

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