Evidence map›Paper›PMID 31858186›Full record

Trial reportDiabetologia2020

An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension.

John P Hanrahan, Jelena P Seferovic, James D Wakefield, Phebe J Wilson, Jennifer G Chickering, Joon Jung, Kenneth E Carlson, Daniel P Zimmer, Andrew L Frelinger, Alan D Michelson and 5 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03091920 (A Phase 2 Study to Compare the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 2 Dose Regimens of IW-1973 in Patients With Stable Type 2 Diabetes and Hypertension), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 8% 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.

NCT03091920 phase2completednot on this map

A Phase 2 Study to Compare the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 2 Dose Regimens of IW-1973 in Patients With Stable Type 2 Diabetes and Hypertension

TypeinterventionalSponsorCyclerion TherapeuticsRan2017 to 2017Enrolled26ConditionsDiabetes Mellitus, Type 2, HypertensionArmsIW-1973, Placebo
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
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  6. Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
    Review
  7. Upcoming drug targets for kidney protective effects in chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
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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

15 authors at 4 institutions in 1 country.

John P HanrahanCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA. JHanrahan@Cyclerion.com.ORCID http://orcid.org/0000-0002-7095-9490
Jelena P SeferovicCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
James D WakefieldCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Phebe J WilsonCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Jennifer G ChickeringCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Joon JungCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Kenneth E CarlsonCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Daniel P ZimmerCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Andrew L FrelingerCenter for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Alan D MichelsonCenter for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Linda MorrowProSciento, Inc., Chula Vista, CA, USA.
Michael HallIronwood Pharmaceuticals, Inc., Cambridge, MA, USA.
Mark G CurrieCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
G Todd MilneCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Albert T ProfyCyclerion Therapeutics, Inc., 301 Binney Street, Cambridge, MA, 02142, USA.
Cyclerion (United States) · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USIronwood Pharmaceuticals (United States) · USPrecision Research Institute · US

Funding

Medical Research Council MC_UU_00006/4Medical Research Council MC_UU_12015/3
6 · The paper itself

Abstract

aims/hypothesisPraliciguat (IW-1973), a soluble guanylate cyclase stimulator, amplifies nitric oxide signalling. This exploratory trial investigated the safety, tolerability, pharmacokinetic profile and pharmacodynamic effects of praliciguat in individuals with type 2 diabetes and hypertension.

methodsThis Phase IIA, double-blind, placebo-controlled trial investigated praliciguat in 26 participants with type 2 diabetes and hypertension on stable glucose- and BP-lowering therapies. Participants were randomly allocated in a 3:5:5 ratio to three groups: placebo (n = 6), praliciguat 40 mg once daily for days 1-14 (n = 10), or praliciguat 20 mg twice daily for days 1-7 then 40 mg once daily for days 8-14 (n = 10). Assessments were made in clinic and included treatment-emergent adverse events, pharmacokinetics, metabolic variables, 24 h BP and heart rate, platelet function, reactive hyperaemia index (RHI) and plasma biomarkers. Participants, the sponsor, the investigator and clinic study staff (except designated pharmacy personnel) were blinded to group assignment.

resultsParticipants treated for 14 days with praliciguat had least-square mean change-from-baseline differences vs placebo (95% CI) of -0.7 (-1.8, 0.4) mmol/l for fasting plasma glucose, -0.7 (-1.1, -0.2) mmol/l for total cholesterol, -0.5 (-1.0, -0.1) mmol/l for LDL-cholesterol, -23 (-56, 9) for HOMA-IR in those not being treated with insulin, and -5 (-10, 1) mmHg and 3 (-1, 6) beats/min for average 24 h mean arterial pressure and heart rate, respectively. Apart from one serious adverse event (SAE; upper gastrointestinal haemorrhage), praliciguat was well tolerated. Praliciguat did not affect platelet function or RHI. Among exploratory biomarkers, plasma levels of asymmetric dimethylarginine decreased in praliciguat vs placebo recipients. CONCLUSIONS/

interpretationIn participants with type 2 diabetes and hypertension on standard therapies, over 14 days praliciguat was well tolerated, except for a single SAE, and showed positive trends in metabolic and BP variables. These results support further clinical investigation of praliciguat.

trial registrationClinicalTrials.gov NCT03091920.

fundingThis trial was funded by Cyclerion Therapeutics.

Indexed as

AdultAgedDiabetes Mellitus, Type 2Diabetic NephropathiesDouble-Blind MethodDrug Therapy, CombinationFemaleGuanylyl Cyclase C AgonistsHumansHypertensionHypoglycemic AgentsInsulinMaleMiddle AgedPyrazolesPyrimidinesGuanylyl Cyclase C AgonistsHypoglycemic AgentsInsulinpraliciguatPyrazolesPyrimidinesBPCyclic guanosine monophosphateEndothelial functionHyperlipidaemiaHypertensionInsulin resistanceSoluble guanylate cyclase stimulatorType 2 diabetes

Identifiers

PMID31858186
PMCPMC7054374
OpenAlexW2995764953

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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 OpenQuestion graph.