A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor

Novo Nordisk A/S2,734 enrolled

Overview

The study will look at how well CagriSema helps people lower their blood sugar and body weight. CagriSema is a new weekly medicine that combines two medicines called semaglutide and cagrilintide. CagriSema will be compared to the two medicines semaglutide and cagrilintide, when they are taken alone. CagriSema will also be compared to a "dummy" medicine without any active ingredient. The study will be done in participants who have type 2 diabetes. Participants will take the study medicine together with the current diabetes medicine (metformin with or without an SGLT2 inhibitor).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,734

Conditions

Type 2 Diabetes Mellitus

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female (sex at birth). * Age 18 years or above at the time of signing the informed consent. * Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening. * Stable daily dose(s) greater than or equal to 90 days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose as judged by the investigator: metformin with or without Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors. * Glycated haemoglobin (HbA1c) 7.0-10.5 percent (53-91 millimoles per mole \[mmol/mol\]) (both inclusive) as determined by central laboratory at screening. * Body Mass Index (BMI) greater than or equal to 25 kilogram per square metre ( kg/m\^2) at screening. BMI will be calculated in the electronic case report form (eCRF) based on height and body weight at screening. Exclusion Criteria: * Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than 30 milliliters per minute per 1.73 square metre (mL/min/1.73 m\^2) as determined by central laboratory at screening. * Treatment with any medication for the indication of diabetes or obesity 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. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation.

Locations (405)

Synexus Clin Res-Birmingham

Birmingham, Alabama, United States

Univ of Alabama_Birmingham

Birmingham, Alabama, United States

Cahaba Research

Pelham, Alabama, United States

Velocity Clinical Research-Phoenix

Phoenix, Arizona, United States

Synexus Rsch /Cnt Phnx Med C

Phoenix, Arizona, United States

Outcomes

Primary Outcomes

CagriSema (dose 1) versus semaglutide (dose 1): Change in glycated haemoglobin (HbA1c)

Measured in percentage-points.

Time frame: From baseline (week 0) to end of treatment (week 68)

Secondary Outcomes

CagriSema versus cagrilintide: Change in HbA1c

Measured in percentage-points.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus cagrilintide: Relative change in body weight

Measured in percentage.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema (dose 1) versus semaglutide (dose 2): Change in HbA1c

Measured in percentage-points.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Relative change in body weight

Measured in percentage.

Time frame: From baseline (week 0) to end of treatment (week 68)

Cagrilintide versus placebo: Change in HbA1c

Measured in percentage-points.

Time frame: From baseline (week 0) to end of treatment (week 68)

Cagrilintide versus placebo: Relative change in body weight

Measured in percentage.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Achievement of greater than or equal to (>=) 10 percent (%) weight reduction

Measured as count of participants.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Achievement of >= 15 % weight reduction

Measured as count of participants.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Achievement of >= 20 % weight reduction

Measured as count of participants.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema (pooled doses) versus semaglutide (pooled doses): Continuous Glucose Monitoring (CGM) - Change in Time in Range (TIR) 3.9-10.0 millimoles per litre (mmol/L) (70-180 milligrams per decilitre [mg/dL])

Measured in percentage-points.

Time frame: From baseline (week -3) to end of treatment (week 68)

CagriSema versus semaglutide: CGM - Change in time in Tight Target Range (TITR) 3.9-7.8 (mmol/L) (70-140 mg/dL)

Measured in percentage-points.

Time frame: From baseline (week -3) to end of treatment (week 68)

CagriSema versus semaglutide: Change in Systolic Blood Pressure (SBP)

Measured in millimeters of mercury (mmHg).

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in triglycerides

Measured as ratio of triglycerides.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in non-High Density Lipoprotein (HDL) cholesterols

Measured as ratio of non-HDL cholesterol.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: CGM - Change in Time In Range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL)

Measured in percentage-points.

Time frame: From baseline (week -3) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in high sensitivity C-Reactive Protein (hsCRP)

Measured as ratio of hsCRP.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Change in Fasting Plasma Glucose (FPG)

Measured in mmol/L.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Achievement of HbA1c target values of less than (<) 7.0% (<53 millimoles per mole [mmol/mol])

Measured as count of participants.

Time frame: At end of treatment (week 68)

CagriSema versus semaglutide: Achievement of HbA1c target values of less than or equal to (≤)6.5% (≤48 mmol/mol)

Measured as count of participants.

Time frame: At end of treatment (week 68)

CagriSema versus semaglutide: CGM - Change in time above range, >10.0 mmol/L (>180 mg/dL)

Measured in percentage-points.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: CGM - Change in time above range, >13.9 mmol/L (>250 mg/dL)

Measured in percentage-points.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: CGM - Within-day glycaemic variability (% coefficient of variation [CV])

Measured in percentage.

Time frame: At end of treatment (week 68)

CagriSema versus semaglutide: Achievement of ≥ 5 % weight reduction

Measured as count of participants.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Change in waist circumference

Measured in centimetre.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Change in Diastolic Blood Pressure (DBP)

Measured in mmHg.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in total cholesterol

Measured as ratio of total cholesterol.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in HDL cholesterol

Measured as ratio of HDL cholesterol.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in low-density lipoprotein (LDL) cholesterol

Measured as ratio of LDL cholesterol.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in very low-density lipoprotein (VLDL) cholesterol

Measured as ratio of VLDL.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Ratio to baseline in free fatty acids

Measured as ratio of free fatty acids.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Change in Short Form (SF)-36v score- Physical component summary score

SF-36v2 measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 acute scores are norm-based scores, i.e. transformed to a scale where the 2009 US general population has a mean of 50 and an standard deviation of 10. Physical component summary score range from 6.1 to 79.7, with higher scores indicating better functional health and well-being.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Change in SF-36v2 score- Mental component summary score

SF-36v2 measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 acute scores are norm-based scores, i.e. transformed to a scale where the 2009 US general population has a mean of 50 and an standard deviation of 10. Mental component summary score range from -3.8 to 78.7, with higher scores indicating better functional health and well-being.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score

DTSQc measures treatment satisfaction and diabetes-specific quality of life (QoL). The measure consists of 8 items yielding 1 global score and 2 single item scores. Total treatment satisfaction scores range from 0-36, with higher scores indicating greater satisfaction; the perceived frequency of hyperglycemia/hypoglycemia items are scored separately, with lower scores indicating better perceived blood glucose control.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide: Change in Treatment Related Impact Measure for Diabetes (TRIM-D) score

TRIM-D measures impact of diabetes treatment. The measure consists of 28 items yielding 5 domain scores and a total score. The scores were transformed to a 0-100 scale with higher scores indicating a better health state.

Time frame: From baseline (week 0) to end of treatment (week 68)

CagriSema versus semaglutide, placebo and cagrilintide: Number of treatment emergent adverse events (TEAEs)

Measured as count of events.

Time frame: From baseline (week 0) to end of study (week 75)

CagriSema versus semaglutide: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)

Measured as count of episodes.

Time frame: From baseline (week 0) to end of study (week 75)

CagriSema versus semaglutide: Number of severe hypoglycaemic episodes (level 3)

Measured as count of episodes. Hypoglycaemia episodes (level 3) are the episodes associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold.

Time frame: From baseline (week 0) to end of study (week 75)