Research Study to Compare Semaglutide Tablets With Empagliflozin or Metformin Tablets in People With Type 2 Diabetes

Phase 3

Withdrawn

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Semaglutide; Drug: Metformin; Drug: Empagliflozin

• Registration Number: NCT06083675
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This study compares the medicines semaglutide with empagliflozin or metformin in people with newly diagnosed type 2 diabetes. This study will look mainly at how well participant's blood sugar and body weight are controlled when they are taking the study medicines. Participants will either get semaglutide tablets, empagliflozin tablets or metformin tablets. Which treatment participants will get is decided by chance. Currently, doses of 3 milligram (mg), 7 mg and 14 mg semaglutide tablets (Rybelsus) can be prescribed in some countries. 25 mg and 50 mg semaglutide tablets are new doses. 10 mg and 25 mg empagliflozin tablets (Jardiance) can be prescribed in some countries. 500 mg metformin tablets (STADA) can be prescribed in some countries. Participants will get 1 to 4 tablets per day for 104 weeks. The study will last for about 2 years and 7 weeks (111 weeks). Participants should not have been treated for weight management 90 days before screening or never been treated with any medicine for type 2 diabetes (except diabetes during pregnancy) before screening. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-09
• Study First Submitted QC: 2023-10-09
• Study First Posted: 2023-10-16
• Study Start: 2024-01-26
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-23
• Last Update Posted: 2024-02-26
• Primary Completion: 2025-01-24
• Study Completion: 2027-05-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Male or female.
• Age ≥18 and <60 years at the time of signing the informed consent.
• Diagnosed with type 2 diabetes mellitus within 24 months from the day of screening.
• HbA1c of 7.0-10.0% (53-86 millimoles per mole [mmol/mol])
• Body mass index ≥25.0 kilogram per square meter (kg/m^2)

Exclusion Criteria

• Treatment with any medication for the indication of diabetes. Prior insulin treatment for gestational diabetes is allowed.
• Treatment with any medication for the indication of weight management 90 days prior to screening.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) <60 milliliters per minute per 1.73 meter sqaure (mL/min/1.73 m^2) at screening.
• 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.
• C-peptide <1.5 nanograms per milliliter (ng/mL) at screening.
• Positive insulinoma associated-protein 2 (IA-2) antibodies ≥7.5 Units/mL or anti-glutamic acid decarboxylase (anti-GAD) antibodies greater than (>) 5.0 international units per milliliter (IU/mL).
• Impaired liver function, defined as Alanine aminotransferase (ALT) ≥2.5 times or Bilirubin >1.5 times upper normal limit at screening.
• History of major surgical procedures involving the stomach potentially affecting absorption of trial products (example subtotal or total gastrectomy, sleeve gastrectomy, gastric bypass surgery) or current presence of gastrointestinal implant.
• Presence of clinically significant gastrointestinal disorders affecting absorption of drugs and/or nutrients, as judged by the investigator.
• Any contraindications for empagliflozin or metformin according to local labelling at the investigator's discretion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semaglutide 25 mg	Semaglutide	Participants will receive 25 mg oral semaglutide once daily in maintenance period after dose escalation period.
Semaglutide 50 mg	Semaglutide	Participants will receive 50 mg oral semaglutide once daily in maintenance period after dose escalation period.
Metformin 2000 mg	Metformin	Participants will receive metformin 1000 mg orally twice daily (total 2000 mg) in maintenance period after dose escalation period.
Empagliflozin 25 mg	Empagliflozin	Participants will 25 mg empagliflozin oral once daily in maintenance period after dose escalation period.

Primary Outcome Measures

Name	Time	Method
Change in glycated haemoglobin (HbA1c)	From randomisation (week 0) to week 52	Measured in Percentage (%)-points.

Secondary Outcome Measures

Name	Time	Method
Change in FPG	From randomisation (week 0) to week 104	Measured in mmol/L.
Relative change in body weight	From randomisation (week 0) to week 104	Measured in Percentage.
HbA1c less than or equal to (≤) 6.5% (Yes/No)	At week 52	Measured as count of participants.
HbA1c less than (<) 7% (Yes/No)	At week 52	Measured as count of participants.
Change in body weight	From randomisation (week 0) to week 104	Measured in kg.
Change in 7 point self measured plasma glucose (SMPG) mean profile	From randomisation (week 0) to week 52	Measured in mmol/L.
Change in 7-point self-measured plasma glucose (SMPG) mean post prandial increments	From randomisation (week 0) to week 52	Measured in mmol/L.
Change in diastolic blood pressure	From randomisation (week 0) to week 104	Measured in mmHg.
Change in waist circumference	From randomisation (week 0) to week 104	Measured in cm.
HbA1c <7.0% and body weight reduction ≥5% (Yes/No)	At week 104	Measured as count of participants.
Body weight reduction greater than equal to ( ≥) 5% (Yes/No)	At week 52	Measured as count of participants.
Change in fasting plasma glucose (FPG)	From randomisation (week 0) to week 52	Measured in millimoles per liter (mmol/L).
Body weight reduction ≥10% (Yes/No)	At week 104	Measured as count of participants.
Body weight reduction ≥15% (Yes/No)	At week 104	Measured as count of participants.
Change in systolic blood pressure	From randomisation (week 0) to week 104	Measured in mmHg.
Change in High-sensitivity C-reactive protein (hsCRP)	From randomisation (week 0) to week 52	Measured in milligrams per liter (mg/L).
Time to rescue medication	From randomisation (week 0) to week 104	Measured in days.
Change in HbA1c	From randomisation (week 0) to week 104	Measured in %-points.
Change in 7 point SMPG mean profile	From randomisation (week 0) to week 104	Measured in mmol/L.
Change in 7-point SMPG mean post prandial increments	From randomisation (week 0) to week 104	Measured in mmol/L
HbA1c ≤6.5% (Yes/No)	At week 104	Measured as count of participants.
HbA1c <7.0% (Yes/No)	At week 104	Measured as count of participants.
Body weight reduction ≥5% (Yes/No)	At week 104	Measured as count of participants.
Change in hsCRP	From randomisation (week 0) to week 104	Measured in mg/L.
Treatment emergent adverse events	From randomisation (week 0) to follow-up visit (week 109)	Measured as count of events.
Number of severe (level 3) or clinically significant (level 2) hypoglycaemic episodes	From randomisation (week 0) to follow-up visit (week 109)	Measured as count of episodes.
Change in Control of Eating Questionnaire (CoEQ) score - Craving Control domain	From randomisation (week 0) to week 52	CoEQ is a 19-item multidimensional patient reported outcome (PRO) that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control.
Change in CoEQ score - Craving for Savory domain	From randomisation (week 0) to week 104	CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving savoury food subscale, higher score represents a greater level of craving.
Change in Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) score - Physical function domain	From randomisation (week 0) to week 52	IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0 100), Physical Function composite (0-100). Total score range (0-100).
Change in American Heart Association (AHA) Life's Simple 7 summary score	From randomisation (week 0) to week 52	The AHA recommends focusing on 7 cardiovascular health factors (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) for early or primary prevention of cardiovascular disease. The 7 health factors are each categorized as ideal, intermediate, or poor. Scales range from 0 (minimum) to 14 (maximum). Higher score represents a greater level of health.
Change in CoEQ score - Craving Control domain	From randomisation (week 0) to week 104	CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control.
Change in IWQOL-Lite-CT score - Physical function domain	From randomisation (week 0) to week 104	IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0 100), Physical Function composite (0-100). Total score range (0-100).
Change in AHA Life's Simple 7 summary score	From randomisation (week 0) to week 104	The AHA recommends focusing on 7 cardiovascular health factors (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) for early or primary prevention of cardiovascular disease. The 7 health factors are each categorized as ideal, intermediate, or poor. Scales range from 0 (minimum) to 14 (maximum). Higher score represents a greater level of health.

Trial Locations

Locations (100)

Hillcrest Family Health Center; 🇺🇸 Waco, Texas, United States

Instituto de Ciências Farmacêuticas; 🇧🇷 Goiânia, Goias, Brazil

Núcleo de Pesquisa Clínica do Rio Grande do Sul Ltda.; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

CPQuali Pesquisa Clínica Ltda; 🇧🇷 São Paulo, Sao Paulo, Brazil

CPCLIN - Centro de Pesquisas Clínicas; 🇧🇷 São Paulo, Sao Paulo, Brazil

Individual Practice For Specialized Outpatient Medical Care Doctor Miglena Rizova Ltd.; 🇧🇬 Kyustendil, Bulgaria

Diagnostic-Consultative Centre "Sveti Georgi" Eood; 🇧🇬 Plovdiv, Bulgaria

"Aipsomcemd - Dr. Petya Georgieva" Eood; 🇧🇬 Plovdiv, Bulgaria

''Aipsomcidemd - Dr. Lilyana Bodurova-Troharova" Eood; 🇧🇬 Samokov, Bulgaria

"Medical center Medishtit Velisia" OOD; 🇧🇬 Stara Zagora, Bulgaria

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