Investigating How NNC0487-0111 Regulates Insulin of Adults With Type 2 Diabetes

Effect of NNC0487-0111 on Insulin Sensitivity and Pancreatic Endocrine Function in Adults With Type 2 Diabetes

The purpose of this clinical study is to find out how NNC0487-0111 affects, how the body uses insulin (a hormone that helps the body control blood sugar) and how well the pancreas works in people living with type 2 diabetes. There are 2 study treatments. Participants will get either NNC0487-0111 (the treatment being tested) or Placebo (a treatment that has no active medicine in it). Which treatment participants get is decided by chance.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: NNC0487-0111; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Recruiting
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female.
• Age 18-75 years (both inclusive) at the time of signing the informed consent.
• Diagnosed with type 2 diabetes more than or equal to (≥)180 days before screening.
• Only stable daily dose(s) of metformin at effective or maximum tolerated dose, as judged by the investigator for at least 90 days before screening. If additional oral antidiabetic drug (OAD) is required, only stable dose(s) of sodium-glucose cotransporter-2 inhibitors (SGLT2i) is permitted, and this must also have been maintained for at least 90 days before screening.
• HbA1c at screening of 6.5-9.5% [48-80 millimole per mole (mmol/mol)] (both inclusive) if on metformin only, or 6.0-9.0% (42-75 mmol/mol) (both inclusive) if on metformin in combination with SGLT2i.

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method.
• Presence of type 1 diabetes.
• Any clinically significant body weight change (≥5% self-reported change) or dieting attempts (e.g., participation in a weight reduction program) within 90 days before screening.
• Treatment with any medication for the indication of T2D or weight management other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed.
• Treatment with a GLP-1 receptor agonist.
• Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) before screening or are expected to require treatment after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
• Presence or history of cardiovascular disease including stable and unstable angina pectoris, myocardial infarction, transient ischaemic attack, stroke, cardiac decompensation, clinically significant arrhythmias or clinically significant conduction disorders within 180 days before screening.
• Renal impairment with estimated glomerular filtration rate (eGFR) less than (<) 60.0 milliliter per minute per meter square (ml/min/1.73 m^2) at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo matched to NNC0487-0111 subcutaneously once weekly.	Drug: Placebo; Placebo matched to NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.
Experimental: NNC0487-0111 dose level 1; Participants will be randomized to receive NNC0487-0111 dose level 1 subcutaneously once weekly.	Drug: NNC0487-0111; NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.
Experimental: NNC0487-0111 dose level 2; Participants will be randomized to receive NNC0487-0111 dose level 2 subcutaneously once weekly.	Drug: NNC0487-0111; NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.
Experimental: NNC0487-0111 dose level 3; Participants will be randomized to receive NNC0487-0111 dose level 3 subcutaneously once weekly.	Drug: NNC0487-0111; NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in M-value in Hyperinsulinaemic euglycaemic clamp (HEC)	Measured as milligram per minute per kilogram (mg/min/kg)	Baseline to week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in M-value in HEC, normalised by lean body mass	Measured as mg/min/kg	Baseline to week 40
Change in first-phase incremental Insulin Secretion Rate (ISR0-8 min) in Hyperglycaemic clamp (HGC)	Measured as picomole per minute per meter square (pmol/min/m^2)	Baseline to week 40
Change in second-phase ISR (ISR20-120 min) in HGC	Measured as pmol/min/m^2	Baseline to week 40
Change in total ISR (ISR0-120 min) in HGC	Measured as pmol/min/m^2	Baseline to week 40
Change in ISR at fixed glucose concentration (ISRg) in HGC	Measured as pmol/min/m^2	Baseline to week 40
Change in total insulin response [total area under curve (AUC0-120) min] in HGC	Measured as picomole per liter per minute (min*pmol/L)	Baseline to week 40
Change in clamp disposition index (cDI) calculated from HEC and HGC	Measured as picomole per liter per meter square per minute square per kilogram (pmol*L/m^2/min^2/kg)	Baseline to week 40
Change in cDI calculated from HEC and HGC, based on lean body mass	Measured as pmol*L/m^2/min^2/kg	Baseline to week 40
Change in β-cell glucose sensitivity (insulin secretion) from HGC	Measured as picomole per minute per meter square per millimoles per liter [pmol/min/m^2/ (mmol/L)]	Baseline to week 40
Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose)	Measured as pmol/min/m^2/ (mmol/L)	Baseline to week 40
Change in glycated haemoglobin (HbA1c)	Measured as percentage (%) of HbA1c	Baseline to week 40

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2026
• Primary Completion (Estimated): November 11, 2027
• Study Completion (Estimated): December 6, 2027

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus
• Other Study ID Numbers: NN9490-8153; U1111-1320-4780 (Other Identifier: World Health Organization (WHO)); 2025-521595-55 (Other Identifier: European Medical Agency (EMA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No