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Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes (SUSTAIN - CHINA MRCT) (SUSTAIN)

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ClinicalTrials.gov Identifier: NCT03061214
Recruitment Status : Completed
First Posted : February 23, 2017
Results First Posted : April 9, 2020
Last Update Posted : March 2, 2021
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This trial is conducted in Africa, Asia, Europe and South America. The aim of the trial is to compare the effect of once-weekly dosing of two dose levels of semaglutide versus sitagliptin 100 mg once-daily on glycaemic control after 30 weeks of treatment. Subjects will remain on their stable pre-trial metformin.

Condition or disease Intervention/treatment Phase
Diabetes Diabetes Mellitus, Type 2 Drug: Semaglutide 0.5 mg Drug: Semaglutide 1.0 mg Drug: Sitagliptin placebo Drug: Sitagliptin Drug: Semaglutide placebo 0.5 mg Drug: Semaglutide placebo 1.0 mg Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 868 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes. A 30-week Randomised, Double-blind, Double-dummy, Active-controlled, Parallel-group, Multi-centre and Multi-national Trial
Actual Study Start Date : August 28, 2017
Actual Primary Completion Date : March 14, 2019
Actual Study Completion Date : April 15, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Semaglutide 0.5 mg OW + sitagliptin placebo OD Drug: Semaglutide 0.5 mg
Up to 0.5 mg semaglutide injected subcutaneously (s.c., under the skin) once-weekly (OW) for 30 weeks

Drug: Sitagliptin placebo
Sitagliptin placebo tablets taken once-daily for 30 weeks

Experimental: Semaglutide 1 mg OW + sitagliptin placebo OD Drug: Semaglutide 1.0 mg
Up to 1.0 mg semaglutide injected subcutaneously once-weekly for 30 weeks

Drug: Sitagliptin placebo
Sitagliptin placebo tablets taken once-daily for 30 weeks

Active Comparator: Sitagliptin OD + semaglutide placebo 0.5 mg OW Drug: Sitagliptin
100 mg sitagliptin tablets taken once-daily for 30 weeks

Drug: Semaglutide placebo 0.5 mg
Semaglutide placebo (0.5 mg) injected subcutaneously once-weekly for 30 weeks

Active Comparator: Sitagliptin OD + semaglutide placebo 1 mg OW Drug: Sitagliptin
100 mg sitagliptin tablets taken once-daily for 30 weeks

Drug: Semaglutide placebo 1.0 mg
Semaglutide placebo (1.0 mg) injected subcutaneously once-weekly for 30 weeks




Primary Outcome Measures :
  1. Change in HbA1c [ Time Frame: Week 0, week 30 ]
    Change from baseline (week 0) to week 30 in glycosylated haemoglobin (HbA1c) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period and 'in trial' observation period. 'On-treatment without rescue medication' observation period: started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. 'In-trial' observation period: started when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature treatment discontinuation.


Secondary Outcome Measures :
  1. Change in Body Weight [ Time Frame: Week 0, week 30 ]
    Change from baseline (week 0) to week 30 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  2. Change in Fasting Plasma Glucose (FPG) [ Time Frame: Week 0, week 30 ]
    Change from baseline (week 0) to week 30 in FPG was evaluated. Results are based on the 'on-treatment without rescue medication' observation period which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  3. Change in Self-measured Plasma Glucose (SMPG) - Mean 7-point Profile [ Time Frame: Week 0, week 30 ]
    Change from baseline (week 0) to week 30 in SMPG mean 7-point profile was evaluated. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  4. Change in Self-measured Plasma Glucose (SMPG) - Mean Postprandial Increment Over All Meals [ Time Frame: Week 0, week 30 ]
    Change from baseline (week 0) to week 30 in SMPG mean postprandial increment over all meals was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  5. Change in Fasting Insulin - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting insulin from baseline (week 0) to week 30 is presented as ratio to baseline. Fasting insulin was measured in picomoles per liter (pmol/L). Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  6. Change in Fasting C-peptide - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting C-peptide from baseline (week 0) to week 30 is presented as ratio to baseline. C-peptide was measured in nanomoles per liter (nmol/L). Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  7. Change in Fasting Glucagon - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting glucagon from baseline (week 0) to week 30 is presented as ratio to baseline. Fasting glucagon was measured in picogram per mililiter (pg/mL). Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  8. Change in Fasting Proinsulin - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting proinsulin from baseline (week 0) to week 30 is presented as ratio to baseline. Fasting proinsulin was measured in picomole per liter (pmol/L). Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  9. Change in Fasting Proinsulin/Insulin Ratio - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting proinsulin/insulin ratio from baseline (week 0) to week 30 is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  10. Change in Fasting HOMA-B (Beta-cell Function) - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting HOMA-B (homeostasis model assessment beta-cell function) from baseline (week 0) to week 30 is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  11. Change in Fasting HOMA-IR (Insulin Resistence) - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting HOMA-IR (homeostasis model assessment insulin resistence) from baseline (week 0) to week 30 is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  12. Change in Patient Reported Outcome Questionnaire: SF-36v2™ Score [ Time Frame: Week 0, week 30 ]
    Short Form (SF)-36 is a 36-item patient-reported survey that measures patient's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured 8 domains of functional health & well-being and 2 component summary scores (physical component summary-PCS and mental component summary-MCS). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 30. A positive change score indicates an improvement since baseline. Results are based on the data from the 'on-treatment without rescue medication' observation period.

  13. Change in Patient Reported Outcome Questionnaire: DTSQs Score [ Time Frame: Week 0, week 30 ]
    Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire (DTSQs) was evaluated at week 30. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 3 -8. For items 1 and 2 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 1) or low (item 2). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 3-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the 'on-treatment without rescue medication' observation period.

  14. Change in High-sensitivity CRP - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in high-sensitivity C-reactive protein (CRP) from baseline (week 0) to week 30 is presented as ratio to baseline. High-sensitivity CRP was measured in mg/L. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  15. Change in Waist Circumference [ Time Frame: Week 0, week 30 ]
    Change in waist circumference from baseline (week 0) to week 30 was measured. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  16. Change in BMI [ Time Frame: Week 0, week 30 ]
    Change in body mass index (BMI) from baseline (week 0) to week 30 was measured. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  17. Change in Fasting Total Cholesterol - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting total cholesterol from baseline (week 0) to week 30 is presented as ratio to baseline. Fasting total cholesterol was measured in mmol/L. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  18. Change in Fasting LDL Cholesterol - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting low density lipoprotein (LDL) from baseline (week 0) to week 30 is presented as ratio to baseline. Fasting LDL was measured in mmol/L. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  19. Change in Fasting VLDL Cholesterol - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting very low density lipoprotein (VLDL) from baseline (week 0) to week 30 is presented as ratio to baseline. Fasting VLDL was measured in mmol/L. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  20. Change in Fasting HDL Cholesterol - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting high density lipoprotein (HDL) from baseline (week 0) to week 30 is presented as ratio to baseline. Fasting HDL was measured in mmol/L. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  21. Change in Fasting Triglycerides - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in fasting triglycerides from baseline (week 0) to week 30 is presented as ratio to baseline. Triglycerides was measured in mmol/L. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  22. Change in Free Fatty Acids - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in free fatty acids from baseline (week 0) to week 30 is presented as ratio to baseline. Free fatty acids was measured in mmol/L. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  23. Change in Blood Pressure (Systolic and Diastolic Blood Pressure) [ Time Frame: Week 0, week 30 ]
    Change from baseline (week 0) to week 30 in systolic blood pressure and diastolic blood pressure were evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  24. Percentage of Participants Who Achieved HbA1c <7.0% (53 mmol/Mol), ADA Target, (Yes/no) [ Time Frame: Week 30 ]
    Percentage of participants who achieved HbA1c < 7.0% (53 millimoles per mole [mmol/mol]), American Diabetes Association (ADA) target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  25. Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/Mol), AACE Target, (Yes/no) [ Time Frame: Week 30 ]
    Percentage of participants who achieved HbA1c ≤6.5% (48 millimoles per mole [mmol/mol]), American Association of Clinical Endocrinologists (AACE) target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  26. Percentage of Participants That Achieved (Yes/no): HbA1c <7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia and no Weight Gain [ Time Frame: Week 30 ]
    Severe or blood glucose (BG)-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 milligrams per deciliter [mg/dL]) with symptoms consistent with hypoglycaemia. Percentage of participants who achieved HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose confirmed symptomatic hypoglycaemia episodes and no weight gain (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  27. Percentage of Participants That Achieved (Yes/no): Body Weight Loss ≥5% [ Time Frame: Week 30 ]
    Percentage of participants losing ≥5% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  28. Percentage of Participants That Achieved (Yes/no): Body Weight Loss ≥10% [ Time Frame: Week 30 ]
    Percentage of participants losing ≥10% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  29. Total Number of Treatment Emergent Adverse Events [ Time Frame: Week 0 to week 30 ]
    A treatment emergent adverse event (TEAE) is defined as an adverse event with onset in the on-treatment observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  30. Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes [ Time Frame: Week 0 to week 30 ]
    Hypoglycaemic episodes are defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  31. Participants With Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes [ Time Frame: Week 0 to week 30 ]
    Number of participants with treatment emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes. Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  32. Change in Haematological Parameter: Haemoglobin - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in haemoglobin from baseline (week 0) to week 30 is presented as ratio to baseline. Haemoglobin was measured in mmol/L. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  33. Change in Haematological Parameter: Haematocrit - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in haematocrit from baseline (week 0) to week 30 is presented as ratio to baseline. Haematocrit was measured in percentage. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  34. Change in Hematological Parameter: Thrombocytes - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in thrombocytes from baseline (week 0) to week 30 is presented as ratio to baseline. Thrombocytes was measured in 10^9 cells per liter. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  35. Change in Hematological Parameter: Erythrocytes - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in erythrocytes from baseline (week 0) to week 30 is presented as ratio to baseline. Erythrocytes were measured in 10^12 cells per liter. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  36. Change in Hematological Parameter: Leukocytes - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in leukocytes from baseline (week 0) to week 30 is presented as ratio to baseline. Leukocytes were measured in 10^9 cells per liter. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  37. Change in Hematological Parameter (Differential Cell Count of Leukocytes): Basophils - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in basophils from baseline (week 0) to week 30 is presented as ratio to baseline. Basophils were measured in percentage. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  38. Change in Hematological Parameter (Differential Cell Count of Leukocytes): Neutrophils - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in neutrophils from baseline (week 0) to week 30 is presented as ratio to baseline. Neutrophils were measured in percentage. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  39. Change in Hematological Parameter (Differential Cell Count of Leukocytes): Eosinophils - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in eosinophils from baseline (week 0) to week 30 is presented as ratio to baseline. Eosinophils were measured in percentage. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  40. Change in Hematological Parameter (Differential Cell Count of Leukocytes): Monocytes - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in monocytes from baseline (week 0) to week 30 is presented as ratio to baseline. Monocytes were measured in percentage. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  41. Change in Hematological Parameter (Differential Cell Count of Leukocytes): Lymphocytes - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in lymphocytes from baseline (week 0) to week 30 is presented as ratio to baseline. Lymphocytes were measured in percentage. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  42. Change in Biochemistry Parameter: Amylase - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in amylase from baseline (week 0) to week 30 is presented as ratio to baseline. Amylase was measured in units per liter (U/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  43. Change in Biochemistry Parameter: Lipase - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in lipase from baseline (week 0) to week 30 is presented as ratio to baseline. Lipase was measured in units per liter (U/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  44. Change in Biochemistry Parameter: Alkaline Phosphatase - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in alkaline phosphatase from baseline (week 0) to week 30 is presented as ratio to baseline. Alkaline phosphatase was measured in units per liter (U/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  45. Change in Biochemistry Parameter: Alanine Aminotransferase - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in alanine aminotransferase from baseline (week 0) to week 30 is presented as ratio to baseline. Alanine aminotransferase was measured in units per liter (U/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  46. Change in Biochemistry Parameter: Aspartate Aminotransferase - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in aspartate aminotransferase from baseline (week 0) to week 30 is presented as ratio to baseline. Aspartate aminotransferase was measured in units per liter (U/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  47. Change in Biochemistry Parameter: Total Bilirubin - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in total bilirubin from baseline (week 0) to week 30 is presented as ratio to baseline. Total bilirubin was measured in micromoles per liter (umol/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  48. Change in Biochemistry Parameter: Calcium (Corrected)- Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in calcium (corrected) from baseline (week 0) to week 30 is presented as ratio to baseline. Calcium was measured in millimoles per litre (mmol/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  49. Change in Biochemistry Parameter: Total Calcium - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in total calcium from baseline (week 0) to week 30 is presented as ratio to baseline. Calcium was measured in millimoles per litre (mmol/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  50. Change in Biochemistry Parameter: Potassium - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in potassium from baseline (week 0) to week 30 is presented as ratio to baseline. Potassium was measured in millimoles per liter (mmol/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  51. Change in Biochemistry Parameter: Sodium - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in sodium from baseline (week 0) to week 30 is presented as ratio to baseline. Sodium was measured in millimoles per litre (mmol/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  52. Change in Biochemistry Parameter: Albumin - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in albumin from baseline (week 0) to week 30 is presented as ratio to baseline. Albumin was measured in grams per deciliter (g/dL). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  53. Change in Biochemistry Parameter: Creatine Kinase - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in creatine kinase from baseline (week 0) to week 30 is presented as ratio to baseline. Creatine kinase was measured in units per liter (U/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  54. Change in Biochemistry Parameter: Total Protein- Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in Total protein from baseline (week 0) to week 30 is presented as ratio to baseline. Total Protein was measured in grams per deciliter (g/dL). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  55. Change in Biochemistry Parameter: Creatinine - Ratio to Baseline [ Time Frame: Week -2, week 30 ]
    Change in creatinine from baseline (week -2) to week 30 is presented as ratio to baseline. Creatinine was measured in micromoles per lier (umol/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  56. Change in Biochemistry Parameter: Urea - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in urea from baseline (week 0) to week 30 is presented as ratio to baseline. Urea was measured in millimoles per liter (mmol/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  57. Change in Biochemistry Parameter: Estimated Glomerular Filtration Rate (eGFR) - Ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in estimated glomerular filtration rate (eGFR) from baseline (week 0) to week 30 is presented as ratio to baseline. Glomerular filtration rate was measured in milliliter/minute/specific surface area (mL/min/SSA). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  58. Change in Calcitonin - Ratio to Baseline [ Time Frame: Week -2, week 30 ]
    Change in calcitonin from baseline (week -2) to week 30 is presented as ratio to baseline. Calcitonin was measured in nanogram per liter (ng/L). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  59. Change in Urinalysis Parameter - UACR-ratio to Baseline [ Time Frame: Week 0, week 30 ]
    Change in urin albumin to creatinine ratio (UACR) from baseline (week 0) to week 30 is presented as ratio to baseline. UACR was measured in milligram/millimole (mg/mmol). Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  60. Change in Urinalysis Parameter: Glucose [ Time Frame: Week 0, week 30 ]
    Glucose in urine was assessed by the investigator and categorised as negative, [100-249], [250-499], [500-999] and >= 1000. Number of participants in each category at baseline (week 0) and week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  61. Change in Urinalysis Parameter: pH [ Time Frame: Week 0, week 30 ]
    pH in urine was assessed by the investigator and categorised as 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, >=9. Number of participants in each category at baseline (week 0) and week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  62. Change in Urinalysis Parameter: Protein [ Time Frame: Week 0, week 30 ]
    Protein in urine was assessed by the investigator and categorised as negative, trace, 30-99, 100-299, Approximately 300, >=300. Number of participants in each category at baseline (week 0) and week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  63. Change in Urinalysis Parameter: Ketones [ Time Frame: Week 0, week 30 ]
    Ketones in urine was assessed by the investigator and categorised as negative, trace, 15-39, 40-79, Approximately 80, >= 80. Number of participants in each category at baseline (week 0) and week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  64. Change in Urinalysis Parameter: Erythrocytes [ Time Frame: Week 0, week 30 ]
    Erythrocytes in urine was assessed by the investigator and categorised as negative, trace, small, moderate, large. Number of participants in each category at baseline (week 0) and week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  65. Change in Clinical Evaluation: Pulse [ Time Frame: Week 0, week 30 ]
    Change in pulse from baseline (week 0) to week 30 is presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  66. Change in Clinical Evaluation: ECG [ Time Frame: Week 0, week 30 ]
    The electrocardiogram (ECG) was assessed by the investigator and categorised as normal, abnormal not clinically significant (NCS) or abnormal clinically significant (CS). Number of participants in each ECG category at baseline and week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  67. Change in Clinical Evaluation: Eye Examinations [ Time Frame: Week 0, week 30 ]
    Eye examination was performed by the investigator and the results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal not clinically significant (NCS) or abnormal clinically significant (CS). Number of participants in each category at baseline (week 0) and at week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  68. Change in Physical Examination [ Time Frame: Week -2, week 30 ]
    Physical examination parameters are categorised as general appearance; nervous system (central and peripheral); cardiovascular system; gastrointestinal system; skin; respiratory system; lymph node palpation; thyroid gland; left foot; right foot; left leg and right leg. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -2) and week 30 are presented. Results are based on the 'on-treatment' observation period. On-treatment observation period is defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  69. Anti-semaglutide Antibody Levels [ Time Frame: week 30, week 35 ]
    This outcome measure is only applicable for the semaglutide arms. Anti-semaglutide antibody level at week 30 and week 35 are presented. Antibody levels were measured in percentage of bound radioactivity-labelled semaglutide/total added radioactivity-labelled semaglutide (%B/T; B =Bound, T = Total). Evaluation was based on 'in trial' observation period, which is the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature treatment discontinuation.

  70. Occurence of Anti-semaglutide Antibodies (Yes/no) [ Time Frame: Week 0, week 16, week 30, week 35 ]
    This outcome measure is only applicable for the semaglutide arms. Development of anti-semaglutide antibodies was evaluated in participants during the study. The number of participants who were positive/ negative for anti-semaglutide antibodies were presented. Evaluation was based on 'in trial' observation period, which is the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature treatment discontinuation.

  71. Occurence of Anti-semaglutide Antibodies With In-vitro Neutralising Effect (Yes/no) [ Time Frame: Week 0, week 16, week 30, week 35 ]
    This outcome measure is only applicable for the semaglutide arms. Development of anti-semaglutide antibodies with in-vitro neutralising effect was evaluated in participants during the study. The number of participants who were positive/ negative for anti-semaglutide antibodies with in vitro neutralising effect are presented. Evaluation was based on in-trial observation period, which is the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature treatment discontinuation.

  72. Occurence of Anti-semaglutide Antibodies Cross Reacting With Endogenous GLP-1 (Yes/no) [ Time Frame: Week 35 ]
    This outcome measure is only applicable for the semaglutide arms. Development of anti-semaglutide antibodies cross reacting with endogenous glucagon-like peptide-1 (GLP-1) was evaluated in participants. The number of participants who were positive/ negative for anti-semaglutide antibodies cross reacting with endogenous GLP-1 are presented. Evaluation was based on in-trial observation period, which is the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature treatment discontinuation.

  73. Occurence of Cross Reacting Antibodies With in Vitro Neutralising Effect to Endogenous GLP-1 (Yes/no) [ Time Frame: Week 35 ]
    This outcome measure is only applicable for the semaglutide arms. Development of cross reacting antibodies with in-vitro neutralising effect to endogenous glucagon-like peptide-1 (GLP-1) was evaluated in participants. The number of participants who were positive/ negative for anti-semaglutide antibodies with in vitro neutralising effect to endogenous GLP-1 are presented. Evaluation was based on in-trial observation period, which is the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature treatment discontinuation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male or female, age equal to or above 18 years at the time of signing informed consent - Subjects diagnosed with type 2 diabetes and on stable treatment in a period of 60 days prior to screening with metformin equal to or above 1500 mg (or maximum tolerated dose equal to or above 1000 mg). Stable is defined as unchanged medication and unchanged daily dose - HbA1c 7.0 - 10.5 % (53-91 mmol/mol) (both inclusive) Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential not using an adequate contraceptive method throughout the trial including the 5 week follow-up period (adequate contraceptive measure as required by local regulation or practice) - Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 60 days before screening. An exception is short-term treatment (equal to or below 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value equal to or above 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association (NYHA) class IV

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03061214


Locations
Show Show 67 study locations
Sponsors and Collaborators
Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:
Study Protocol  [PDF] August 22, 2019
Statistical Analysis Plan  [PDF] August 22, 2019

Publications of Results:
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03061214    
Other Study ID Numbers: NN9535-4114
U1111-1149-0432 ( Other Identifier: World Health Organization (WHO) )
CTR20161003 ( Registry Identifier: China Drug Trials (China) )
First Posted: February 23, 2017    Key Record Dates
Results First Posted: April 9, 2020
Last Update Posted: March 2, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action