Clinical trial NCT06403761: Investigating How CagriSema, Semaglutide and Cagrilintide Regulate Insulin Effects in the Body of People With Type 2 Diabetes
Official title: Effect of CagriSema, Semaglutide and Cagrilintide on Insulin Sensitivity and Pancreatic Endocrine Function in Adults With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2024-05-08
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will look at how CagriSema, semaglutide and cagrilintide regulate insulin effects in the body of people with type 2 diabetes (T2D). CagriSema is a new investigational medicine that combines two medicines called cagrilintide and semaglutide. Doctors may not yet prescribe CagriSema. Participants will either get CagriSema, semaglutide, cagrilintide, or a ''dummy'' medicine. Which treatment the participants will get is decided by chance. Participants will get the study medicine together with the current daily diabetes medicine metformin. Participants should not take other medicines for diabetes during the study. The study will last for about 42 weeks.


Eligibility criteria: Inclusion Criteria:

* Male or female.
* Aged 18-75 years (both inclusive) at the time of signing informed consent.
* Diagnosed with type 2 diabetes greater than or equal to (\>=) 180 days before screening.
* Stable daily dose(s) of metformin at effective or maximum tolerated dose, as judged by the investigator for 90 or more days before screening with or without one additional oral antidiabetic drug (OAD), except for the use of glucagon-like peptide-1 (GLP-1) receptor agonists, or sodium-glucose co-transporter-2 (SGLT-2) inhibitors in case of a high risk of cardiovascular disease (as judged by the investigator), or established cardiovascular disease, or chronic kidney disease (Glomerular Filtration Rate (eGFR) less than (\<) 60 milliliter per minute per 1.73 square meter \[ml/min/1.73 m\^2\]).
* Glycated hemoglobin (HbA1c) at screening of 6.5-9.5 percent (48-80 millimoles per mole \[mmol/mol\]) (both inclusive) if on metformin only, or 6.0- 9.0 percent (42-75 mmol/mol) (both inclusive) if on metformin in combination with one other OAD. A minimum of 65% of randomised participants must have HbA1c \>= 7.0 % at screening.
* Body Mass index (BMI) between 25.0 and 45.0 kilogram per square meter (kg/m\^2) (both inclusive) at screening.

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.
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus 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.
* Renal impairment with estimated Glomerular Filtration Rate (eGFR) \< 45 ml/min/1.73 m\^2 at 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.

Primary outcomes:
measure: To compare the effect of CagriSema versus placebo: Change in M-value in hyperinsulinaemic euglycaemic clamp (HEC)
timeFrame: Baseline to week 28
Secondary outcomes:
measure: To compare the effect of CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC
timeFrame: Baseline to week 28
measure: To compare the effect of CagriSema versus placebo, CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC, normalised by lean body mass
timeFrame: Baseline to week 28
measure: Change in first-phase incremental insulin secretion rate (ISR0-8min) in hyperglycaemic clamp (HGC)
timeFrame: Baseline to week 28
measure: Change in second-phase insulin secretion rate (ISR20-120min) in HGC
timeFrame: Baseline to week 28
measure: Change in total insulin secretion rate (ISR0-120min) in HGC
timeFrame: Baseline to week 28
measure: Change in insulin secretion rate at fixed glucose concentration (ISRg) in HGC
timeFrame: Baseline to week 28
measure: Change in total insulin response (total AUC0-120 min) in HGC
timeFrame: Baseline to week 28
measure: Change in insulin response to arginine (incremental insulin AUCarginine,0-10min) in HGC
timeFrame: Baseline to week 28
measure: Change in C-peptide response to arginine (incremental insulin AUCarginine,0-10min) in HGC
timeFrame: Baseline to week 28
measure: Change in clamp disposition index (cDI) calculated from HEC and HGC
timeFrame: Baseline to week 28
measure: Change in cDI calculated from HEC and HGC,based on lean body mass
timeFrame: Baseline to week 28
measure: Change in β-cell glucose sensitivity (insulin secretion) from HGC
timeFrame: Baseline to week 28
measure: Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose)
timeFrame: Baseline to week 28
measure: Change in glucose concentration during MMTT (total and incremental AUC0-300min)
timeFrame: Baseline to week 28
measure: Change in insulin concentration during MMTT (total and incremental AUC0-300min)
timeFrame: Baseline to week 28
measure: Change in C-peptide concentration during MMTT (total and incremental AUC0-300min)
timeFrame: Baseline to week 28
measure: Change in glucagon concentration during MMTT (total and incremental AUC0-300min)
timeFrame: Baseline to week 28
measure: Change in fasting glucose concentration (MMTT pre-meal concentrations)
timeFrame: Baseline to week 28
measure: Change in fasting insulin concentration (MMTT pre-meal concentrations)
timeFrame: Baseline to week 28
measure: Change in fasting C-peptide concentration (MMTT pre-meal concentrations)
timeFrame: Baseline to week 28
measure: Change in fasting glucagon concentration (MMTT pre-meal concentrations)
timeFrame: Baseline to week 28
measure: Change in fasting proinsulin concentration (MMTT pre-meal concentrations)
timeFrame: Baseline to week 28
measure: Change in HbA1c
timeFrame: Baseline to week 28
measure: Change in systolic and diastolic blood pressure
timeFrame: Baseline to week 28
measure: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline to end of study (week 34)
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: