Type 2 Diabetes Mellitus
Conditions
Brief summary
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).
Interventions
DRUGCagrilintide
Participants will receive once-weekly s.c injection of cagrilintide at escalating doses every week until maintenance dose 1 and dose 2 of cagrilintide is reached.
DRUGSemaglutide
Participants will receive once-weekly s.c injection of semaglutide at escalating doses every week until maintenance dose 1 and dose 2 of semaglutide is reached.
Participants will receive placebo matched to cagrilintide subcutaneously.
Participants will receive placebo matched to semaglutide subcutaneously.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CagriSema (dose 1) versus semaglutide (dose 1): Change in glycated haemoglobin (HbA1c) | From baseline (week 0) to end of treatment (week 68) | Measured in percentage-points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CagriSema versus cagrilintide: Change in HbA1c | From baseline (week 0) to end of treatment (week 68) | Measured in percentage-points. |
| CagriSema versus cagrilintide: Relative change in body weight | From baseline (week 0) to end of treatment (week 68) | Measured in percentage. |
| CagriSema (dose 1) versus semaglutide (dose 2): Change in HbA1c | From baseline (week 0) to end of treatment (week 68) | Measured in percentage-points. |
| CagriSema versus semaglutide: Relative change in body weight | From baseline (week 0) to end of treatment (week 68) | Measured in percentage. |
| Cagrilintide versus placebo: Change in HbA1c | From baseline (week 0) to end of treatment (week 68) | Measured in percentage-points. |
| Cagrilintide versus placebo: Relative change in body weight | From baseline (week 0) to end of treatment (week 68) | Measured in percentage. |
| CagriSema versus semaglutide: Achievement of greater than or equal to (>=) 10 percent (%) weight reduction | From baseline (week 0) to end of treatment (week 68) | Measured as count of participants. |
| CagriSema versus semaglutide: Achievement of >= 15 % weight reduction | From baseline (week 0) to end of treatment (week 68) | Measured as count of participants. |
| 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]) | From baseline (week -3) to end of treatment (week 68) | Measured in percentage-points. |
| CagriSema versus semaglutide: CGM - Change in time in Tight Target Range (TITR) 3.9-7.8 (mmol/L) (70-140 mg/dL) | From baseline (week -3) to end of treatment (week 68) | Measured in percentage-points. |
| CagriSema versus semaglutide: Change in Systolic Blood Pressure (SBP) | From baseline (week 0) to end of treatment (week 68) | Measured in millimeters of mercury (mmHg). |
| CagriSema versus semaglutide: Ratio to baseline in triglycerides | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of triglycerides. |
| CagriSema versus semaglutide: Ratio to baseline in non-High Density Lipoprotein (HDL) cholesterols | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of non-HDL cholesterol. |
| CagriSema versus semaglutide: CGM - Change in Time In Range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL) | From baseline (week -3) to end of treatment (week 68) | Measured in percentage-points. |
| CagriSema versus semaglutide: Ratio to baseline in high sensitivity C-Reactive Protein (hsCRP) | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of hsCRP. |
| CagriSema versus semaglutide: Change in Fasting Plasma Glucose (FPG) | From baseline (week 0) to end of treatment (week 68) | Measured in mmol/L. |
| CagriSema versus semaglutide: Achievement of HbA1c target values of less than (<) 7.0% (<53 millimoles per mole [mmol/mol]) | At end of treatment (week 68) | Measured as count of participants. |
| CagriSema versus semaglutide: Achievement of HbA1c target values of less than or equal to (≤)6.5% (≤48 mmol/mol) | At end of treatment (week 68) | Measured as count of participants. |
| CagriSema versus semaglutide: CGM - Change in time above range, >10.0 mmol/L (>180 mg/dL) | From baseline (week 0) to end of treatment (week 68) | Measured in percentage-points. |
| CagriSema versus semaglutide: CGM - Change in time above range, >13.9 mmol/L (>250 mg/dL) | From baseline (week 0) to end of treatment (week 68) | Measured in percentage-points. |
| CagriSema versus semaglutide: CGM - Within-day glycaemic variability (% coefficient of variation [CV]) | At end of treatment (week 68) | Measured in percentage. |
| CagriSema versus semaglutide: Achievement of ≥ 5 % weight reduction | From baseline (week 0) to end of treatment (week 68) | Measured as count of participants. |
| CagriSema versus semaglutide: Change in waist circumference | From baseline (week 0) to end of treatment (week 68) | Measured in centimetre. |
| CagriSema versus semaglutide: Change in Diastolic Blood Pressure (DBP) | From baseline (week 0) to end of treatment (week 68) | Measured in mmHg. |
| CagriSema versus semaglutide: Ratio to baseline in total cholesterol | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of total cholesterol. |
| CagriSema versus semaglutide: Ratio to baseline in HDL cholesterol | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of HDL cholesterol. |
| CagriSema versus semaglutide: Ratio to baseline in low-density lipoprotein (LDL) cholesterol | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of LDL cholesterol. |
| CagriSema versus semaglutide: Ratio to baseline in very low-density lipoprotein (VLDL) cholesterol | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of VLDL. |
| CagriSema versus semaglutide: Ratio to baseline in free fatty acids | From baseline (week 0) to end of treatment (week 68) | Measured as ratio of free fatty acids. |
| CagriSema versus semaglutide: Change in Short Form (SF)-36v score- Physical component summary score | From baseline (week 0) to end of treatment (week 68) | 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. |
| CagriSema versus semaglutide: Change in SF-36v2 score- Mental component summary score | From baseline (week 0) to end of treatment (week 68) | 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. |
| CagriSema versus semaglutide: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score | From baseline (week 0) to end of treatment (week 68) | 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. |
| CagriSema versus semaglutide: Change in Treatment Related Impact Measure for Diabetes (TRIM-D) score | From baseline (week 0) to end of treatment (week 68) | 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. |
| CagriSema versus semaglutide, placebo and cagrilintide: Number of treatment emergent adverse events (TEAEs) | From baseline (week 0) to end of study (week 75) | Measured as count of events. |
| CagriSema versus semaglutide: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) | From baseline (week 0) to end of study (week 75) | Measured as count of episodes. |
| CagriSema versus semaglutide: Achievement of >= 20 % weight reduction | From baseline (week 0) to end of treatment (week 68) | Measured as count of participants. |
| CagriSema versus semaglutide: Number of severe hypoglycaemic episodes (level 3) | From baseline (week 0) to end of study (week 75) | 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. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Czechia, Denmark, Finland, Germany, Greece, Hungary, India, Israel, Italy, Japan, Mexico, Poland, Romania, Serbia, Slovakia, Slovenia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Outcome results
None listed