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Trial · Interventional

CompletedPhase 3Registry data

A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)

NCTNCT05013229 (opens ClinicalTrials.gov in a new tab)Other idNN1535-4593Other idU1111-1260-8295Other id2020-005309-18Other idjRCT2051210127

This trial does not test a peptide that PepBank tracks.

  • Names Semaglutide, does not test it. It appears in the title.

Overview

Status
Completed
Phase
Phase 3
Enrollment
679 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Open label (no masking)
Countries
14 countries

United States, Czechia, France, Germany, Hungary, India, Italy, Japan, Malaysia, Poland, Slovenia, South Africa, Thailand, Turkey (Türkiye)

Start
30 Nov 2021
Primary completion
14 Nov 2023
Completion
14 Nov 2023
First posted
19 Aug 2021
Last update posted
2 Dec 2025
Conditions
Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024
  1. Ph 3

    A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)

    NCT05013229

    30 Nov 2021 to 14 Nov 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine taken daily with insulin aspart in people with type 2 diabetes.The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to insulin glargine taken with insulin aspart. Participants will either get IcoSema or insulin glargine taken with insulin aspart. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine and insulin aspart in many countries. Participants will get IcoSema or insulin glargine together with insulin aspart. Participants must inject IcoSema once a week or inject insulin glargine once daily and insulin aspart 2-4 times a day. Participants will inject the medicines with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach. The study will last for about 1 year and 1 month. Participants will be asked to wear a sensor that measures participants blood sugar level all the time during an 8 week period at the beginning of the study and a 4 week period at the end of the study. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Interventions

  • IcoSemaDrug
  • Insulin glargineDrug
  • insulin aspartDrug

Arms2

  • Experimental

    IcoSema

    Participants will receive once weekly subcutaneous (s.c) injections of IcoSema during the 52-week treatment period.

  • Active comparator

    Insuling glargine/insulin aspart

    Participants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in HbA1c

    Time frame · From baseline week 0 (V2) to week 52 (V54)

    Registry description

    Percent-points

Secondary outcomes(10)
  1. Change in body weight

    Time frame · From baseline week 0 (V2) to week 52 (V54)

    Registry description

    Kg

  2. Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)

    Time frame · From week 0 (V52) to week 52 (V54)

    Registry description

    Number of episodes

  3. Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6

    Time frame · From week 48 (V50) to week 52 (V54)

    Registry description

    Percentage of readings

  4. Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6

    Time frame · From week 48 (V50) to week 52 (V54)

    Registry description

    Percentage of readings

  5. Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6

    Time frame · From week 48 (V50) to week 52 (V54)

    Registry description

    Percentage of readings

  6. Change in fasting plasma glucose (FPG)

    Time frame · From baseline week 0 (V2) to week 52 (V54)

    Registry description

    mmol/L

  7. Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction

    Time frame · From baseline week 0 (V2) to week 52 (V54)

    Registry description

    Score 0-36. The higher the score the greater the satisfaction with treatment.

  8. Number of severe hypoglycaemic episodes (level 3)

    Time frame · From baseline week 0 (V2) to week 57 (V56)

    Registry description

    Number of episodes

  9. Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter)

    Time frame · From baseline week 0 (V2) to week 57 (V56)

    Registry description

    Number of episodes

  10. Weekly insulin dose (total)

    Time frame · From week 50 (V52) to week 52 (V54)

    Registry description

    Units

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

Completed trials do not always post results.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2026

7 results

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

Ji et al. 2026Diabetes, obesity & metabolismcited by 1

PMID 42557064PMC13538793DOI 10.1111/dom.70895PUB-42557064

Free to read · publisher termsCC BY-NC7 results

Indexing hint: Randomized controlled trial · 2025

5 results

Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial.

Billings et al. 2025The lancet. Diabetes & endocrinologycited by 19

PMID 40482670DOI 10.1016/s2213-8587(25)00052-xPUB-40482670

Full text at the publisher5 results

More studies

1 study on this page

PubMed tag: none · 2026

CGM-derived postprandial glucose with IcoSema versus other insulin regimens: a post hoc analysis of COMBINE 1 and 3.

De Block et al. 2026EClinicalMedicine

PMID 42306490PMC13266221DOI 10.1016/j.eclinm.2026.103985PUB-42306490

Free to read · publisher termsCC BY-NC-ND
Read at source

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Male or female and age above or equal to 18 years at the time of signing informed consent. * Diagnosed with type 2 diabetes mellitus 180 days or more before screening. * HbA1c of 7.0-10.0 percentage (53.- 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening. * Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti diabetic drugs with stable doses 90 days or more before screening: * Metformin * Sulfonylureas(a) * Meglitinides (glinides)(a) * DPP-4 inhibitors(a) * Sodium-glucose co-transporter 2 inhibitors * Alpha-glucosidase-inhibitors * Thiazolidinediones * Marketed oral combination products only including the products listed above. * Body mass index (BMI) less than or equal to 40.0 kg/m\^2. 1. Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation. 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. * Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid, hormones, or systemic corticosteroids). * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. * Any episodes of diabetic ketoacidosis within 90 days before screening. As declared by the participant or in the medical records. * Presence or history of pancreatitis (acute or chronic) within 180 days before screening. * Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening. * Chronic heart failure classified as being in New York Heart Association Class IV at screening. * Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 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.

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