GLP-1 Evidence

Not medical advice. A record of published research and our assessments of it. The limits

Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity

Design
Randomized trial · 99 participants · Biomarker outcome
Match to healthy normal-weight adults aged 55–75
Different population[Auto] Participants had obesity/overweight (age/BMI not reported in abstract).
Could weight loss explain it?
Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
Study tier
Study tier 3[Auto] Small or short randomized trial (auto-provisional).
Assessment
Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026

Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.

[Auto, unreviewed; quoted from abstract conclusions] Although treatment with NN1177 was associated with dose-dependent and clinically relevant weight loss, the observed safety signals precluded further clinical development.

01Findings

What the study reported

Drugs
Class unspecified
Route
subcutaneous
Comparator
placebo
Primary outcome
Not extracted
Effect
Not extracted
95% confidence interval
Not extracted
Follow-up
Not stated
Adverse events
Not extracted
Limitations
Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.

Who was studied

Obesity status
obesity/overweight present (all or most)
Sample size
99

Study quality details

Study design
Randomized controlled trial
Sample size
99
Randomization
yes
Blinding
double-blind
Comparator
placebo
Follow up duration
not stated
Outcome type
biomarker
Replication
not assessed (auto)
Consistency with other evidence
not assessed (auto)
Population applicability
INDIRECT
Statistical precision
not extracted
Risk of bias
not assessed (auto)
Funding conflicts
unclear
Peer review status
yes
02Funding

Funding and conflicts

Funding
not reported in abstract
Industry funded
Unclear
Manufacturer
Novo Nordisk
Sponsor role
not reported in abstract
Author conflicts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Martin Friedrichsen, Lars Endahl, Frederik Kreiner, Søren Toubro and Sune Nygård are employees of Novo Nordisk A/S. Martin Friedrichsen, Lars Endahl and Frederik Kreiner are shareholders in Novo Nordisk A/S. Martin Kankam has received funding from Diffusion Pharmaceutical Inc., Grifols, Urovant Sciences, ViroDefense, Merck, PhaseBio Pharmaceuticals, Inc., Idorsia Pharmaceuticals Ltd, DynPort Vaccine company/FDA/NIH, and Aerovate Therapeutics. Ronald Goldwater is an employee of Parexel International.
Independent replication
unknown

Funding is shown on every study and never used to score it.

04Source

The source, as retrieved

Abstract

[OBJECTIVE] Glucagon/glucagon-like peptide-1 (GLP-1) receptor co-agonists may provide greater weight loss than agonists targeting the GLP-1 receptor alone. We report results from three phase 1 trials investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of the glucagon/GLP-1 receptor co-agonist NNC9204-1177 (NN1177) for once-weekly subcutaneous use in adults with overweight or obesity. [METHODS] Our focus was a 12-week, multiple ascending dose (MAD), placebo-controlled, double-blind trial in which adults (N = 99) received NN1177 (on an escalating dose regimen of 200, 600, 1300, 1900, 2800, 4200 and 6000 μg) or placebo. Two other trials also contributed to the findings reported in this article: a first human dose (FHD)/single ascending dose (SAD), placebo-controlled, double-blind trial in which adults (N = 49) received NN1177 (treatment doses of 10, 40, 120, 350, 700 and 1100 μg) or placebo, and a drug-drug interaction, open-label, single-sequence trial in which adults (N = 45) received a 4200-μg dose of NN1177, following administration of a Cooperstown 5 + 1 index cocktail. Safety, tolerability, pharmacokinetic and pharmacodynamic endpoints were assessed. [RESULTS] For the FHD/SAD and MAD trials, baseline characteristics were generally balanced across treatment cohorts. The geometric mean half-life of NN1177 at steady state was estimated at between 77 and 111 h, and clinically relevant weight loss was achieved (up to 12.6% at week 12; 4200 μg in the MAD trial). Although NN1177 appeared tolerable across trials, several unexpected treatment-related safety signals were observed; increased heart rate, decreased reticulocyte count, increased markers of inflammation (fibrinogen and C-reactive protein), increased aspartate and alanine aminotransferase, impaired glucose tolerance and reduced blood levels of some amino acids. [CONCLUSION] Although treatment with NN1177 was associated with dose-dependent and clinically relevant weight loss, the observed safety signals precluded further clinical development.

Where this record came from

SourceRetrievedIdentifier
pubmedSep 13, 202637690519
first ingestion