Evidence mapPaperPMID 42168649Full record

Trial reportDiabetologia2026

Effect of somatostatin receptor 2 antagonism on glucagon counterregulation during a hyperinsulinaemic euglycaemic-hypoglycaemic glucose clamp in adult men and women with long-standing type 1 diabetes: a randomised crossover phase 1 study.

Alexander Abitbol, Michael C Riddell, Susan Peers, Eric Simonson, Mark Evans, Filip K Knop, Richard T Liggins

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase I
In one paragraph

Trial report in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05007977 (Pharmacodynamic Evaluation of ZT-01 in a Stepped Hypoglycemic Clamp Model in Subjects With Type 1 Diabetes Mellitus), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
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.

NCT05007977 phase1terminatednot on this map

Pharmacodynamic Evaluation of ZT-01 in a Stepped Hypoglycemic Clamp Model in Subjects With Type 1 Diabetes Mellitus

TypeinterventionalSponsorZucara Therapeutics Inc.Ran2021 to 2022Enrolled24ConditionsType 1 Diabetes, HypoglycemiaArmsZT-01 low dose, ZT-01 high dose, Placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Alexander AbitbolLMC Diabetes & Endocrinology, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-6830-3532
Michael C RiddellLMC Diabetes & Endocrinology, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-6556-7559
Susan PeersZucara Therapeutics Inc., Toronto, ON, Canada.
Eric SimonsonZucara Therapeutics Inc., Vancouver, BC, Canada.ORCID http://orcid.org/0009-0007-5071-1299
Mark EvansInstitute of Metabolic Science and Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-8122-8987
Filip K KnopCenter for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.ORCID http://orcid.org/0000-0002-2495-5034
Richard T LigginsZucara Therapeutics Inc., Vancouver, BC, Canada. rliggins@zucara.ca.ORCID http://orcid.org/0009-0004-6591-9269

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisThe aim of this study was to determine the effect of a novel somatostatin receptor 2 (SSTR2) antagonist, ZT-01, on impaired glucagon counterregulation in hypoglycaemia and its safety in adults with type 1 diabetes.

methodsIn a randomised crossover phase 1b single-site study, blinded to both participants and researchers, participants, aged 18-65 years with BMI 18.5-27 kg/m

resultsTwenty-four randomised participants (9 female and 15 male) received at least one administration of placebo or ZT-01 and were included for safety analysis. Twenty-two participants completed at least one glucose clamp and were included for pharmacodynamics analysis. Transient increases in plasma glucagon were observed with ZT-01 administration (by 25.7 ± 2.4 ng/l with 3 mg ZT-01 and by 28.4 ± 2.4 ng/l with 20 mg ZT-01), with levels declining to near the pre-dose values before the start of the level 1 hypoglycaemic period. Mean glucagon levels rose again over baseline in both ZT-01 treatment arms during level 1 (by 15.6 ± 2.3 pg/l with 3 mg ZT-01 and by 14.9 ± 2.4 pg/l with 20 mg ZT-01) and level 2 (by 22.8 ± 2.7 pg/l with 3.0 mg ZT-01 and by 29.6 ± 2.8 pg/l with 20 mg ZT-01) hypoglycaemia. With placebo, glucagon levels were unchanged following dosing and during level 1 hypoglycaemia but rose modestly during level 2 hypoglycaemia (by 8.9 ± 2.5 ng/l). Both frequency and amplitude of the increases in glucagon were higher with ZT-01 vs placebo during level 1 and level 2 hypoglycaemia. There were no drug treatment-related adverse events. CONCLUSIONS/

interpretationAdministration of the SSTR2 antagonist ZT-01 increased glucagon responsiveness during insulin-induced hypoglycaemia in individuals with type 1 diabetes.

trial registrationClinicalTrials.gov NCT05007977.

Indexed as

Diabetes Mellitus, Type 1GlucagonReceptors, SomatostatinAdolescentAdultAgedBlood GlucoseC-PeptideCross-Over StudiesFemaleGlucose Clamp TechniqueHumansHypoglycemiaInsulinMaleMiddle AgedBlood GlucoseC-PeptideGlucagonInsulinReceptors, Somatostatinsomatostatin receptor 2CounterregulationGlucagonGlucose clampSomatostatin receptor antagonist

Identifiers

PMID42168649
PMCPMC13310225

What Socratic holds

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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 Socratic graph.