Evidence mapPaperPMID 31089754Full record

ReviewDiabetologia2019

Neprilysin inhibition: a new therapeutic option for type 2 diabetes?

Nathalie Esser, Sakeneh Zraika

Open access · bronzeAbstract readReview
In one paragraph

Review in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 64 citations in OpenAlex.

  1. Trial
  2. Comparison between sacubitril/valsartan and thiazide diuretics among patients with uncontrolled hypertension in Japan.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
    Article
  3. Article
  4. Dual ETFundamental & clinical pharmacology · 2025
    Article
  5. Impact of Sitagliptin on Neprilysin and Glycemic Control in Newly Diagnosed Type 2 Diabetes Patients.Medical science monitor : international medical journal of experimental and clinical research · 2025
    Article
  6. Article
  7. BOLD MRI to Evaluate the Effects of Sacubitril/Valsartan on Renal Protection in Type 2 Diabetics.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Article
  8. Article
  9. Article
  10. Metabolic and Immunological Implications of MMEBiological procedures online · 2024
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Nathalie EsserVeterans Affairs Puget Sound Health Care System, 1660 South Columbian Way (151), Seattle, WA, 98108, USA.
Sakeneh ZraikaVeterans Affairs Puget Sound Health Care System, 1660 South Columbian Way (151), Seattle, WA, 98108, USA. zraikas@uw.edu.ORCID http://orcid.org/0000-0003-4831-7034
University of Washington · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · 1986 to 2025
$12.6M
NIDDK NIH HHS P30 DK017047NIDDK NIH HHS R01 DK098506
6 · The paper itself

Abstract

Neprilysin is a widely expressed peptidase with broad substrate specificity that preferentially hydrolyses oligopeptide substrates, many of which regulate the cardiovascular, nervous and immune systems. Emerging evidence suggests that neprilysin also hydrolyses peptides that play an important role in glucose metabolism. In recent studies in humans, a dual angiotensin receptor-neprilysin inhibitor (ARNi) improved glycaemic control and insulin sensitivity in individuals with type 2 diabetes and/or obesity. Moreover, preclinical studies have also reported that neprilysin inhibition, alone or in combination with renin-angiotensin system blockers, elicits beneficial effects on glucose homeostasis. Since neprilysin inhibitors have been approved for the treatment of heart failure, their repurposing for treating type 2 diabetes would provide a novel therapeutic strategy. In this review, we evaluate existing evidence from preclinical and clinical studies in which neprilysin is deleted/inhibited, we highlight potential mechanisms underlying the beneficial glycaemic effects of neprilysin inhibition, and discuss possible deleterious effects that may limit the efficacy and safety of neprilysin inhibitors in the clinic. We also review the favourable impact neprilysin inhibition can have on diabetic complications, in addition to glucose control. Finally, we conclude that neprilysin inhibitors may be a useful therapeutic option for treating type 2 diabetes; however, their combination with angiotensin II receptor blockers is needed to circumvent deleterious consequences of neprilysin inhibition alone.

Indexed as

Angiotensin Receptor AntagonistsAnimalsAntihypertensive AgentsAntineoplastic AgentsBlood GlucoseDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsHumansNeprilysinRenin-Angiotensin SystemAngiotensin Receptor AntagonistsAntihypertensive AgentsAntineoplastic AgentsBlood GlucoseDipeptidyl-Peptidase IV InhibitorsNeprilysinGLP-1Insulin resistanceInsulin secretionNeprilysinObesityReviewType 2 diabetes

Identifiers

PMID31089754
PMCPMC6579747
OpenAlexW2945728284

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.