A Randomised Controlled Clinical Trial in Type 2 Diabetes Comparing Semaglutide to Placebo and Liraglutide
- Conditions
- DiabetesDiabetes Mellitus, Type 2
- Interventions
- Registration Number
- NCT00696657
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
This trial was conducted in Europe,Asia and Africa. Study participants were randomised evenly to treatment with semaglutide (0.1 mg QW - 1.6 mg QW, 6 treatment arms, placebo or liraglutide (1.2 mg QD, or 1.8 mg QD).Treatment allocation to semaglutide or placebo was double-blind, whereas liraglutide treatment was administered open-label.Primary efficacy parameter was HbA1c and the treatment duration was 12 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 415
- Men and women-not-of-childbearing potential diagnosed with type 2 diabetes for at least three months
- Stable treatment regimen with either metformin (at least 1500 mg) or diet and exercise alone for at least three months
- HbA1c: 7.0-10.0 % (both inclusive)
- Body weight between 60 kg and 110 kg
- Treatment with insulin, GLP-1 receptor agonists (including liraglutide), dipeptidyl peptidase-4 inhibitors, sulphonylurea, thiazolidinediones, Alpha-GIs, or any investigational drug, within the last three months
- Impaired liver or kidney function
- Proliferative retinopathy or maculopathy requiring acute treatment
- Clinically significant active cardiovascular disease and uncontrolled treated/untreated hypertension
- Recurrent major hypoglycaemia or hypoglycaemic unawareness
- Present or planned use of any drug which could interfere with the glucose levels (e.g. systemic corticosteroids)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description G5 placebo - G1 placebo - G3 placebo - G4 placebo - G2 placebo - G6 placebo - A semaglutide - B semaglutide - C semaglutide - F semaglutide - D semaglutide - E semaglutide - H liraglutide - I liraglutide -
- Primary Outcome Measures
Name Time Method HbA1c After 12 weeks of treatment. Change from baseline in HbA1c was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the last observation carried forward (LOCF) approach.
- Secondary Outcome Measures
Name Time Method Change From Baseline in ECG Week 0, week 12. A standard 12 lead electrocardiogram (ECG) with a 10-second rhythm strip was performed at screening (week -2) and at the end of treatment (week 12). The time frame should be read as "week -2, week 12". Change from baseline in ECG was measured in terms of number of subjects in each category (normal, abnormal, not clinically significant \[NCS\] or abnormal clinically significant \[CS\]) at week -2 and week 12 (i.e., change in each category in terms of number of subjects from week -2 to week 12).
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Sodium) Week 0, week 12. Change from baseline in sodium was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Eosinophils) Week 0, week 12 Change from baseline in eosinophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Lymphocytes) Week 0, week 12 Change from baseline in lymphocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Percentage of Subjects With an Adverse Events After 12 weeks of treatment. The results of adverse event presented here are treatment emergent, i.e., TEAE. A TEAE was defined as an event that had onset on or after the first date (week 0) on trial product and no later than 5 weeks after the last date on trial product (week 17), or that had onset before the first date on trial product and increases in severity during the treatment period until 5 weeks after the last date on trial product.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Haematocrit) Week 0, week 12 Change from baseline in haematocrit (the proportion of blood that consists of red blood cells) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Haemoglobin) Week 0, week 12 Change from baseline in haemoglobin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Albumin) Week 0, week 12. Change from baseline in albumin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Creatinine) Week 0, week 12. Change from baseline in creatinine was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Vital Signs (Pulse) Week 0, week 12 Change from baseline in pulse was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Monocytes) Week 0, week 12 Change from baseline in monocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Neutrophils) Week 0, week 12 Change from baseline in neutrophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Leukocytes) Week 0, week 12 Change from baseline in leukocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Calcium, Total) Week 0, week 12. Change from baseline in calcium, total was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Potassium) Week 0, week 12. Change from baseline in potassium was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Percentage of Subjects With Hypoglycaemic Episode After 12 weeks of treatment The results of hypoglycaemic episode presented here are treatment emergent. Hypoglycaemic episodes were defined as treatment emergent if they had onset on or after the first day of randomised treatment (in week 0) and no later than 5 weeks after the last date on trial product (week 17). Hypoglycaemic episodes are classified as follows: Major: If the subject was not able to treat himself or herself and was needed to be administered food, glucagon or intravenous (i.v.) glucose by another person. Minor: If the subject was able to treat himself or herself and measured plasma glucose was \<3.1 mmol/L (56 mg/dL). Symptoms only: If the subject was able to treat himself or herself and measured plasma glucose was \>=3.1 mmol/L (56 mg/dL) or no plasma glucose measurement was done.
Change From Baseline in Vital Signs (Blood Pressure; SBP) Week 0, week 12 Change from baseline in systolic blood pressure (SBP) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Vital Signs (Blood Pressure; DBP) Week 0, week 12 Change from baseline in diastolic blood pressure (DBP) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Basophils) Week 0, week 12 Change from baseline in basophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; ALAT) Week 0, week 12. Change from baseline in alanine aminotransferase (ALAT) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Protein) Week 0, week 12 Change from baseline in urine-protein was measured in terms of number of subjects in each category at week 0 (negative, 0.3 g/L, 1.0 g/L and missing) and week 12 (negative, trace, 0.3 g/L, 1.0 g/L, \>=3.0 g/L and missing). i.e., change in each category in terms of number of subjects from week 0 to week 12.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Thrombocytes) Week 0, week 12 Change from baseline in thrombocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Erythrocytes) Week 0, week 12 Change from baseline in erythrocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Alkaline Phosphatase) Week 0, week 12. Change from baseline in alkaline phosphatase was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; AST) Week 0, week 12. Change from baseline in aspartate aminotransferase (AST) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Total Bilirubin) Week 0, week 12. Change from baseline in total bilirubin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Calcium, Ionised) Week 0, week 12. Change from baseline in calcium, ionised was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Urea) Week 0, week 12. Change from baseline in urea was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Glucose) Week 0, week 12 Change from baseline in urine-glucose was measured in terms of number of subjects in each category (negative, positive, \>=55 mmol/L, or missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
Change From Baseline in Calcitonin Week 0, week 12. Change from baseline in calcitonin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.
Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Haemoglobin) Week 0, week 12 Change from baseline in urine-haemoglobin was measured in terms of number of subjects in each category (negative, trace, small, moderate/large and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Ketones) Week 0, week 12 Change from baseline in urine-ketone was measured in terms of number of subjects in each category (negative, positive, \>=55 mmol/L and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
Percentage of Subjects Developing Anti-semaglutide Antibodies After 12 weeks of treatment Antibodies were measured after 12-week of treatment at week 17; percentage of participants with positive anti-semaglutide antibodies are presented here. Assessments of antibodies were not done for subjects allocated to the open-label liraglutide treatment arms.
Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; pH) Week 0, week 12 Change from baseline in urine-pH was measured in terms of number of subjects in each category (pH=6.0, 6.5, 7.0, 7.5, 8.0, \>=8.5 and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).
Trial Locations
- Locations (1)
Novo Nordisk Investigational Site
🇬🇧Trowbridge, United Kingdom