A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy

Efficacy and Safety of co Administered Cagrilintide and Semaglutide (CagriSema) Once Weekly Versus Placebo in Participants With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy

This study will look at the effects of CagriSema in people with both type 2 diabetes and painful diabetic peripheral neuropathy, compared to placebo. Participants will either get an active medicine or a "dummy" medicine (placebo). Which treatment participants get is decided by chance. In this study the active, investigational medicine is called CagriSema. Doctors cannot yet prescribe CagriSema. For each participant, the study will last for about 10 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 2; Diabetic Peripheral Neuropathy
• Intervention / Treatment: Drug: CagriSema (Cagrilintide B and Semaglutide I); Drug: Placebo matched to CagriSema (Cagrilintide B and Semaglutide I)

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • G.A. Research Associates Ltd.
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C6
      • Centricity Research Brampton
    • Burlington, Ontario, Canada, L7M 4Y1
      • Centricity Clinical Research Burlington
    • Etobicoke, Ontario, Canada, M9R 4E1
      • Centricity Research Etobicoke
    • Hamilton, Ontario, Canada, L8L 5G4
      • Premier Clinical Trial Research Network (PCTRN)
    • Toronto, Ontario, Canada, M6G 1M2
      • Diabetes Heart Research Centre
  • Quebec
    • Terrebonne, Quebec, Canada, J6X 4P7
      • Ctr de méd métab de Lanaudière
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Steno Diabetes Center Aarhus
  • Gistrup, Denmark, 9260
    • Steno Diabetes Center Nordjylland
  • Herlev, Denmark, 2730
    • Steno Diabetes Center Copenhagen
  • Kolding, Denmark, 6000
    • Kolding Sygehus Karkirurgi
  • Odense C, Denmark, 5000
    • Steno Diabetes Center Odense
• France
  • Le Coudray, France, 28630
    • Les Hopitaux de Chartres-Hopital Louis Pasteur
  • Le Creusot, France, 71200
    • Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1
  • Paris, France, 75013
    • Aphp-Hopital La Pitie Salpetriere-1
  • Pessac, France, 33600
    • Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-1
  • Vénissieux, France, 69200
    • Centre de Recherche Clinique Portes Du Sud
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssykehus
  • Hamar, Norway, 2318
    • Sykehuset Innlandet HF Hamar
  • Oslo, Norway, 0450
    • Oslo universitetssykehus, Ullevål
  • Stavanger, Norway, NO-4011
    • Stavanger Universitetssykehus, Helse Stavanger HF
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Seville, Spain, 41010
    • Hospital Infanta Luisa
  • Andalusia
    • Castilleja de La Cuesta. Sevilla, Andalusia, Spain, 41950
      • Hospital Nisa Sevilla Aljarafe
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
• United Kingdom
  • Ipswich, United Kingdom, IP4 5PD
    • Ipswich Hospital - Diabetes
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital
  • London, United Kingdom, EC2Y 8EA
    • St Pancras Clinical Research
  • London, United Kingdom, SW9 8RR
    • Kings College Hospital - Renal
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary - Diabetes
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital
  • Greater Manchester
    • Ashton-under-Lyne, Greater Manchester, United Kingdom, OL6 9RW
      • Tameside General Hospital
• United States
  • California
    • La Mesa, California, United States, 91942
      • eStudySite
    • San Diego, California, United States, 92111
      • Linda Vista Health Care Ctr
  • Florida
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
    • Miami, Florida, United States, 33155
      • My Preferred Research
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
  • Illinois
    • Springfield, Illinois, United States, 62704
      • Foot & Ankle Center of Illinois
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Velocity Clinical Research Rockville
  • Missouri
    • St Louis, Missouri, United States, 63128
      • Amicis Centers of Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • DM Clinical - CyFair
  • New York
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group, LLP
  • North Carolina
    • Statesville, North Carolina, United States, 28625
      • Piedmont Healthcare/Research
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Rhode Island
    • Cumberland, Rhode Island, United States, 02864
      • Clinical Res Collaborative
  • Texas
    • Houston, Texas, United States, 77081
      • DM Clinical - CyFair
    • Lampasas, Texas, United States, 76550
      • Radiance Clinical Research
    • San Antonio, Texas, United States, 78207
      • DM Clinical Research
    • San Antonio, Texas, United States, 78207
      • DM Clinical - CyFair
  • Virginia
    • Suffolk, Virginia, United States, 23435
      • Velocity Clinical Research Portsmouth

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Male or female.
• Age 18 years or above at the time of signing the informed consent.
• Body mass index (BMI) ≥25.0 kilogram per square meter (kg/m^2) at screening.

• Diagnosis of type 2 diabetes (T2D) ≥180 days before screening.

  -- For participants on anti-diabetic drugs: Stable daily and/or weekly dose(s) ≥90 days before screening of any of the following anti-diabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose, as judged by the investigator:

  • Treatment with 1-3 marketed oral anti-diabetic drugs (OADs) (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitors (SGLT2i), thiazolidinediones, or sulphonylureas (SU) as a single agent or in combination) according to local guidelines.
  • Treatment with basal or basal-bolus insulin (including premixed insulin formulations) according to local guidelines.
• HbA1c ≤10.5 % (91 millimole per mole [mmol/mol]) and ≥6.0 % (42 mmol/mol), as determined by central laboratory at screening.

• Diagnosis of painful diabetic peripheral neuropathy (pDPN) at screening as well as at the following criteria:

  -- Participant with self-reported pain consistent with pDPN for a minimum of 3 months before screening, as judged by the investigator.

• Stable pharmacological and non-pharmacological treatment of pain for a minimum of 3 months before screening, in the opinion of the investigator. The treatment regimen should adhere to local guidelines (if available).

Key Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
• Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), including medication with GLP-1 RA activity, (DPP-4), or amylin analogue within 60 days before screening.
• Significant use of opioids, cannabinoids or benzodiazepines within 30 days before screening, in the opinion of the investigator. Significant use is defined as use that renders it unlikely that the participant is able to comply with protocol requirements for discouraged medications.
• Anticipated initiation or clinically relevant change in concomitant medications (for more than 14 consecutive days during the study) known to affect weight or glucose metabolism (e.g., orlistat, thyroid hormones or oral corticosteroids).
• Planned initiation or change in anti-depressant, anti-psychotic or anti-epileptic medication. If participants are already taking such medication, they should have stable and optimised treatment for at least 8 weeks before screening.
• Presence or history of epilepsy and fibromyalgia.
• Presence of non-diabetic neuropathies, in the opinion of the investigator.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination and OCT assessment 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.
• Any other painful medical condition(s) where the pain is significantly more severe than the diabetic peripheral neuropathy pain, as judged by the investigator (participants will not be excluded if the pain is transient in nature).
• History of suicidal attempt within 5 years before screening
• Suicidal behaviour within 1 month before screening.
• Renal impairment with estimated Glomerular Filtration Rate (eGFR) <30 ml/min/1.73 m2 as determined by central laboratory at screening.
• Exposure to an investigational medicinal product within 90 days or 5 half-lives of the investigational medicinal product (if known), whichever is longer, before screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo matched to CagriSema (Cagrilintide B + Semaglutide I) subcutaneously once weekly for 32 weeks.	Drug: Placebo matched to CagriSema (Cagrilintide B and Semaglutide I); Placebo matched to Cagrilintide B and Placebo matched to Semaglutide I will be administered subcutaneously using DV3384 pen-injector.
Experimental: CagriSema; Participants will receive CagriSema (Cagrilintide B + Semaglutide I) subcutaneously once weekly for 32 weeks.	Drug: CagriSema (Cagrilintide B and Semaglutide I); Cagrilintide B and Semaglutide I will be administered subcutaneously using DV3384 pen-injector.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weekly average Pain Intensity-Numerical Rating Scale (PI-NRS)	Measured as score on a scale.	From baseline (week 0) to end of treatment (week 32)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in systolic blood pressure	Measured as millimeters of mercury (mmHg).	From baseline (week 0) to end of treatment (week 32)
Change in diastolic blood pressure	Measured as mmHg.	From baseline (week 0) to end of treatment (week 32)
Change in glycated haemoglobin (HbA1c)	Measured as percentage of HbA1c.	From baseline (week 0) to end of treatment (week 32)
Change in Fasting Plasma Glucose (FPG)	Measured as millimole per liter (mmol/L).	From baseline (week 0) to end of treatment (week 32)
Relative change in body weight	Measured as percentage change.	From baseline (week 0) to end of treatment (week 32)
Change in waist circumference	Measured as centimeter (cm).	From baseline (week 0) to end of treatment (week 32)
Ratio to Baseline in Lipids: Total Cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 32)
Ratio to Baseline in Lipids: High-density lipoprotein (HDL) cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 32)
Ratio to Baseline in Lipids: Low-density lipoprotein (LDL) cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 32)
Ratio to Baseline in Lipids: Very low-density lipoprotein (VLDL) cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 32)
Ratio to Baseline in Lipids: Triglycerides	Measured as ratio.	From baseline (week 0) to end of treatment (week 32)
Ratio to Baseline in Lipids: Free fatty acids	Measured as ratio.	From baseline (week 0) to end of treatment (week 32)
Ratio to Baseline in Lipids: Non-HDL cholesterol	Measured as ratio.	From baseline (week 0) to end of treatment (week 32)
Relative change in high sensitivity C-reactive protein (hsCRP)	Measured as percentage change.	From baseline (week 0) to end of treatment (week 32)
Number of treatment-emergent adverse events (TEAEs)	Measured as count of events.	From baseline (week 0) to end of study (week 38)
Number of treatment-emergent serious adverse events (TESAEs)	Measured as count of events.	From baseline (week 0) to end of study (week 38)
Number of severe hypoglycaemic episodes (level 3) (No specific glucose threshold)	Severe hypoglycaemia is a severe event characterised by altered mental and/or physical status requiring assistance from another person to actively administer carbohydrates, glucagon, or take other corrective actions to treat hypoglycaemia. Measured as count of episodes.	From baseline (week 0) to end of study (week 38)
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by blood glucose meter))	Measured as count of episodes.	From baseline (week 0) to end of study (week 38)
Number of participants reaching ≥30 percentage (%) reduction in PI-NRS	Measured as count of participants.	From baseline (week 0) to end of treatment (week 32)
Time to achieve ≥30% reduction in weekly average PI-NRS	Measured as days.	From baseline (week 0) to end of treatment (week 32)
Number of participants reaching ≥50 % reduction in PI-NRS	Measured as count of participants.	From baseline (week 0) to end of treatment (week 32)
Time to achieve ≥50% reduction in weekly average PI-NRS	Measured as days.	From baseline (week 0) to end of treatment (week 32)
Change in Brief Pain Inventory-Short Form (BPI-SF)	Measured as score on a scale.	From baseline (week 0) to end of treatment (week 32)
Change in Chronic Pain Sleep Inventory 3-item (CPSI 3)	Measured as score on a scale.	From baseline (week 0) to end of treatment (week 32)
Change in Michigan Neuropathy Screening Instrument (MNSI)	Measured as score on a scale.	From baseline (week 0) to end of treatment (week 32)

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): January 29, 2025
• Primary Completion (Estimated): August 21, 2026
• Study Completion (Estimated): August 21, 2026

Study Registration Dates

• First Submitted: January 27, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): January 29, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: NN9388-7864; U1111-1306-9422 (Other Identifier: World Health Organization (WHO)); 2023-509662-38 (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: Yes
• Studies a U.S. FDA-regulated device product: No