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Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus. (PIONEER 7)

Primary Purpose

Diabetes, Diabetes Mellitus, Type 2

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

semaglutide

sitagliptin

About this trial

This is an interventional treatment trial for Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Main phase (the inclusion criteria for the main phase are not reassessed for the extension phase):

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 above or equal to 18 years at the time of signing informed consent. For Korea only: Male or female, age above or equal to 19 years at the time of signing informed consent
Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening
HbA1c (glycosylated haemoglobin) 7.5-9.5% (58-80 mmol/mol) (both inclusive)
Treatment target of HbA1c below 7.0% (53 mmol/mol), as judged by the investigator
Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening:
Metformin (equal or above 1500 mg or maximum tolerated dose as documented in the subject medical record)
Sulfonylureas (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)
Sodium glucose co-transporter 2 inhibitors
Thiazolidinediones (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

Extension phase:

Informed consent for the extension phase obtained before any trial-related activities for the extension phase.
On randomised treatment with or without rescue medication at week 52.

Exclusion Criteria:

Main phase (the exclusion criteria for the main phase are not reassessed for the extension phase):

Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply
Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma
History of pancreatitis (acute or chronic)
History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation
Subjects presently classified as being in New York Heart Association Class IV
Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
Subjects with alanine aminotransferase above 2.5 x upper normal limit
Renal impairment defined as Estimated Glomerular Filtration rate 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula
Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days
Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation
History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
History of diabetic ketoacidosis

Extension phase: There are no new exclusion criteria for the extension phase

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Semaglutide flexible dosing (3, 7 or 14 mg)

Sitagliptin 100 mg

Arm Description

Outcomes

Primary Outcome Measures

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)

Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Secondary Outcome Measures

Change in Body Weight

Change from baseline (week 0) in body weight was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Change in HbA1c

Change from baseline (week 0) in HbA1c was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in FPG

Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Body Weight (%)

Relative change from baseline (week 0) in body weight (kg) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in BMI

Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Waist Circumference

Change from baseline (week 0) in waist circumference was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Total Cholesterol (Ratio to Baseline)

Change from baseline (week 0) in total cholesterol (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in LDL Cholesterol (Ratio to Baseline)

Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in HDL Cholesterol (Ratio to Baseline)

Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Triglycerides (Ratio to Baseline)

Change from baseline (week 0) in triglycerides (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two 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 week 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

Change in DTSQ

Change from baseline (week 0) in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 52. 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 1, 4 -8. For items 2 and 3 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 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)

Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve Weight Loss ≥5% (Yes/no)

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve Weight Loss ≥10% (Yes/no)

Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 52 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time to Rescue Medication

Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 52. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Time to Additional Anti-diabetic Medication

Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 0 to week 52. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Number of TEAEs During Exposure to Trial Product

Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)

Change in Amylase (Ratio to Baseline)

Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Lipase (Ratio to Baseline)

Change from baseline (week 0) in lipase (U/L) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Pulse Rate

Change from baseline (week 0) in pulse rate was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)

Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in HbA1c- Switch

Change from week 52 in HbA1c was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Body Weight- Switch

Change from week 52 in body weight was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Body Weight (%)- Switch

Relative change from week 52 in body weight (kg) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in FPG- Switch

Change from week 52 in fasting plasma glucose (FPG) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in BMI- Switch

Change from week 52 in body mass index (BMI) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Waist Circumference- Switch

Change from week 52 in waist circumference was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Switch

Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Switch

Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve Weight Loss ≥5% (Yes/no)- Switch

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Switch

Participants who achieved HbA1c less than 7.0% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target and no Need for Rescue Medication (Yes/no)- Switch

Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) and no need for rescue medication (yes/no), was evaluated at week 104. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Time to Additional Anti-diabetic Medication- Switch

Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 53 to week 104. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after re-randomisation (week 52) and before (planned) end-of-treatment (week 104), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time to Rescue Medication- Switch

Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 53 to week 104. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after re-randomisation (week 52) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Number of TEAEs During Exposure to Trial Product- Switch

Treatment emergent adverse events (TEAEs) were recorded from week 53 to week 109. Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Amylase (Ratio to Baseline)- Switch

Change from week 52 in biochemical parameter- amylase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Lipase (Ratio to Baseline)- Switch

Change from week 52 in lipase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Pulse Rate- Switch

Change from week 52 in pulse rate was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Switch

Change from week 52 in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes- Switch

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Switch

Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Switch

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two 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 week 52 in the domain scores and component summary (PCS and MCS) scores were evaluated at week 104. A positive change score indicates an improvement since week 52. Results are based on the data from the in-trial observation period.

Change in DTSQ- Switch

Change from week 52 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. 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 1, 4 -8. For items 2 and 3 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 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.

Change in HbA1c- Sustainability

Change from baseline (week 0) in HbA1c was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Body Weight (kg)- Sustainability

Change from baseline (week 0) in body weight was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Body Weight (%)- Sustainability

Relative change from baseline (week 0) in body weight (kg) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in FPG- Sustainability

Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in BMI- Sustainability

Change from baseline (week 0) in body mass index (BMI) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Waist Circumference- Sustainability

Change from baseline (week 0) in waist circumference was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Sustainability

Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Sustainability

Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve Weight Loss ≥5% (Yes/no)- Sustainability

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Sustainability

Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target or HbA1c Reduction ≥ 1%-Point (10.9 mmol/Mol) (Yes/no)- Sustainability

Participants who achieved HbA1c <7.0% ADA target or HbA1c reduction ≥ 1%-point (10.9 mmol/mol) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Number of TEAEs During Exposure to Trial Product- Sustainability

Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Amylase (Ratio to Baseline)- Sustainability

Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Lipase (Ratio to Baseline)- Sustainability

Change from baseline (week 0) in lipase (U/L) to week 104 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Pulse Rate- Sustainability

Change from baseline (week 0) in pulse rate was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Sustainability

Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes)- Sustainability

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Sustainability

Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Sustainability

Short form (SF)-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two 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 week 104. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

Change in DTSQ- Sustainability

Change from week 0 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. 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 1, 4 -8. For items 2 and 3 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 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.

Full Information

NCT ID

NCT02849080

First Posted

July 21, 2016

Last Updated

July 11, 2022

Sponsor

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT02849080

Brief Title

Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.

Acronym

PIONEER 7

Official Title

Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

September 20, 2016 (Actual)

Primary Completion Date

February 28, 2018 (Actual)

Study Completion Date

March 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This trial is globally conducted. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes, Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

504 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Semaglutide flexible dosing (3, 7 or 14 mg)

Arm Type

Experimental

Arm Title

Sitagliptin 100 mg

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

semaglutide

Intervention Description

Oral administration once-daily.

Intervention Type

Drug

Intervention Name(s)

sitagliptin

Intervention Description

Oral administration once-daily.

Primary Outcome Measure Information:

Title

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)

Description

Time Frame

Week 52

Secondary Outcome Measure Information:

Title

Change in Body Weight

Description

Time Frame

Week 0, week 52

Title

Change in HbA1c

Description

Time Frame

Week 0, week 52

Title

Change in FPG

Description

Time Frame

Week 0, week 52

Title

Change in Body Weight (%)

Description

Time Frame

Week 0, week 52

Title

Change in BMI

Description

Time Frame

Week 0, Week 52

Title

Change in Waist Circumference

Description

Time Frame

Week 0, week 52

Title

Change in Total Cholesterol (Ratio to Baseline)

Description

Time Frame

Week 0, Week 52

Title

Change in LDL Cholesterol (Ratio to Baseline)

Description

Time Frame

Week 0, week 52

Title

Change in HDL Cholesterol (Ratio to Baseline)

Description

Time Frame

Week 0, week 52

Title

Change in Triglycerides (Ratio to Baseline)

Description

Time Frame

Week 0, week 52

Title

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

Description

Time Frame

Week 0, week 52

Title

Change in DTSQ

Description

Time Frame

Week 0, Week 52

Title

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)

Description

Time Frame

Week 52

Title

Participants Who Achieve Weight Loss ≥5% (Yes/no)

Description

Time Frame

Week 52

Title

Participants Who Achieve Weight Loss ≥10% (Yes/no)

Description

Time Frame

Week 52

Title

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Description

Time Frame

Week 52

Title

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Description

Time Frame

Week 52

Title

Time to Rescue Medication

Description

Time Frame

Weeks 0-52

Title

Time to Additional Anti-diabetic Medication

Description

Time Frame

Weeks 0-52

Title

Number of TEAEs During Exposure to Trial Product

Description

Time Frame

Week 0-57

Title

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Description

Time Frame

Week 0-57

Title

Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)

Description

Time Frame

Week 0-57

Title

Change in Amylase (Ratio to Baseline)

Description

Time Frame

Week 0, Week 52

Title

Change in Lipase (Ratio to Baseline)

Description

Time Frame

Week 0, Week 52

Title

Change in Pulse Rate

Description

Time Frame

Week 0, week 52

Title

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)

Description

Time Frame

Week 0, week 52

Title

Change in HbA1c- Switch

Description

Time Frame

Week 52, week 104

Title

Change in Body Weight- Switch

Description

Time Frame

Week 52, week 104

Title

Change in Body Weight (%)- Switch

Description

Time Frame

Week 52, week 104

Title

Change in FPG- Switch

Description

Time Frame

Week 52, week 104

Title

Change in BMI- Switch

Description

Time Frame

Week 52, Week 104

Title

Change in Waist Circumference- Switch

Description

Time Frame

Week 52, week 104

Title

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Switch

Description

Time Frame

Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Title

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Switch

Description

Time Frame

Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Title

Participants Who Achieve Weight Loss ≥5% (Yes/no)- Switch

Description

Time Frame

Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Title

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Switch

Description

Time Frame

Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Title

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target and no Need for Rescue Medication (Yes/no)- Switch

Description

Time Frame

Week 104 (i.e., after 52 weeks of treatment in the extension phase)

Title

Time to Additional Anti-diabetic Medication- Switch

Description

Time Frame

Weeks 53-104

Title

Time to Rescue Medication- Switch

Description

Time Frame

Weeks 53-104

Title

Number of TEAEs During Exposure to Trial Product- Switch

Description

Time Frame

Week 53-109

Title

Change in Amylase (Ratio to Baseline)- Switch

Description

Time Frame

Week 52, Week 104

Title

Change in Lipase (Ratio to Baseline)- Switch

Description

Time Frame

Week 52, Week 104

Title

Change in Pulse Rate- Switch

Description

Time Frame

Week 52, week 104

Title

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Switch

Description

Time Frame

Week 52, week 104

Title

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes- Switch

Description

Time Frame

Week 53-109

Title

Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Switch

Description

Time Frame

Week 53-109

Title

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Switch

Description

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two 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 week 52 in the domain scores and component summary (PCS and MCS) scores were evaluated at week 104. A positive change score indicates an improvement since week 52. Results are based on the data from the in-trial observation period.

Time Frame

Week 52, week 104

Title

Change in DTSQ- Switch

Description

Time Frame

Week 52, week 104

Title

Change in HbA1c- Sustainability

Description

Time Frame

Week 0, week 104

Title

Change in Body Weight (kg)- Sustainability

Description

Time Frame

Week 0, week 104

Title

Change in Body Weight (%)- Sustainability

Description

Time Frame

Week 0, week 104

Title

Change in FPG- Sustainability

Description

Time Frame

Week 0, week 104

Title

Change in BMI- Sustainability

Description

Time Frame

Week 0, Week 104

Title

Change in Waist Circumference- Sustainability

Description

Time Frame

Week 0, week 104

Title

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Sustainability

Description

Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time Frame

Week 104

Title

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Sustainability

Description

Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time Frame

Week 104

Title

Participants Who Achieve Weight Loss ≥5% (Yes/no)- Sustainability

Description

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time Frame

Week 104

Title

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Sustainability

Description

Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time Frame

Week 104

Title

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target or HbA1c Reduction ≥ 1%-Point (10.9 mmol/Mol) (Yes/no)- Sustainability

Description

Time Frame

Week 104

Title

Number of TEAEs During Exposure to Trial Product- Sustainability

Description

Time Frame

Week 0-109

Title

Change in Amylase (Ratio to Baseline)- Sustainability

Description

Time Frame

Week 0, week 104

Title

Change in Lipase (Ratio to Baseline)- Sustainability

Description

Time Frame

Week 0, Week 104

Title

Change in Pulse Rate- Sustainability

Description

Time Frame

Week 0, week 104

Title

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Sustainability

Description

Time Frame

Week 0, week 104

Title

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes)- Sustainability

Description

Time Frame

Week 0-109

Title

Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Sustainability

Description

Time Frame

Week 0-109

Title

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)- Sustainability

Description

Time Frame

Week 0, week 104

Title

Change in DTSQ- Sustainability

Description

Time Frame

Week 0, week 104

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Main phase (the inclusion criteria for the main phase are not reassessed for the extension phase): 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 above or equal to 18 years at the time of signing informed consent. For Korea only: Male or female, age above or equal to 19 years at the time of signing informed consent Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening HbA1c (glycosylated haemoglobin) 7.5-9.5% (58-80 mmol/mol) (both inclusive) Treatment target of HbA1c below 7.0% (53 mmol/mol), as judged by the investigator Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening: Metformin (equal or above 1500 mg or maximum tolerated dose as documented in the subject medical record) Sulfonylureas (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) Sodium glucose co-transporter 2 inhibitors Thiazolidinediones (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) Extension phase: Informed consent for the extension phase obtained before any trial-related activities for the extension phase. On randomised treatment with or without rescue medication at week 52. Exclusion Criteria: Main phase (the exclusion criteria for the main phase are not reassessed for the extension phase): Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma History of pancreatitis (acute or chronic) History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation Subjects presently classified as being in New York Heart Association Class IV Planned coronary, carotid or peripheral artery revascularisation known on the day of screening Subjects with alanine aminotransferase above 2.5 x upper normal limit Renal impairment defined as Estimated Glomerular Filtration rate 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ) History of diabetic ketoacidosis Extension phase: There are no new exclusion criteria for the extension phase

Facility Information:

Facility Name

Novo Nordisk Investigational Site

City

Glendale

State/Province

Arizona

ZIP/Postal Code

85306-4652

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85050

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Lancaster

State/Province

California

ZIP/Postal Code

93534

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

West Hills

State/Province

California

ZIP/Postal Code

91304

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Boynton Beach

State/Province

Florida

ZIP/Postal Code

33472

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Lake Worth

State/Province

Florida

ZIP/Postal Code

33461

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Miami Lakes

State/Province

Florida

ZIP/Postal Code

33014

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Port Orange

State/Province

Florida

ZIP/Postal Code

32127

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33607

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33614

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30318

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Blackfoot

State/Province

Idaho

ZIP/Postal Code

83221

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Evanston

State/Province

Illinois

ZIP/Postal Code

60201-2477

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Greenfield

State/Province

Indiana

ZIP/Postal Code

46140

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Muncie

State/Province

Indiana

ZIP/Postal Code

47304

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40213

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70002

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Oxon Hill

State/Province

Maryland

ZIP/Postal Code

20745

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Flint

State/Province

Michigan

ZIP/Postal Code

48504

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Billings

State/Province

Montana

ZIP/Postal Code

59101

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Henderson

State/Province

Nevada

ZIP/Postal Code

89052-2649

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87109-2134

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27514

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Greensboro

State/Province

North Carolina

ZIP/Postal Code

27408

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Greenville

State/Province

North Carolina

ZIP/Postal Code

27834

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Whiteville

State/Province

North Carolina

ZIP/Postal Code

28472

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44122

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Mentor

State/Province

Ohio

ZIP/Postal Code

44060

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Wadsworth

State/Province

Ohio

ZIP/Postal Code

44281

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15236

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Murrells Inlet

State/Province

South Carolina

ZIP/Postal Code

29576

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Myrtle Beach

State/Province

South Carolina

ZIP/Postal Code

29572

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Kingsport

State/Province

Tennessee

ZIP/Postal Code

37660

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Corpus Christi

State/Province

Texas

ZIP/Postal Code

78413

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Chesapeake

State/Province

Virginia

ZIP/Postal Code

23321

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Renton

State/Province

Washington

ZIP/Postal Code

98057

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Caba

ZIP/Postal Code

C1180AAX

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Corrientes

ZIP/Postal Code

3400

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Rosario

ZIP/Postal Code

S2000DNM

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

Novo Nordisk Investigational Site

City

Saint Stefan

ZIP/Postal Code

8511

Country

Austria

Facility Name

Novo Nordisk Investigational Site

City

Wien

ZIP/Postal Code

1130

Country

Austria

Facility Name

Novo Nordisk Investigational Site

City

Bonheiden

ZIP/Postal Code

2820

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Boussu

ZIP/Postal Code

7300

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Edegem

ZIP/Postal Code

2650

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

Liège

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Novo Nordisk Investigational Site

City

São Paulo

State/Province

Sao Paulo

ZIP/Postal Code

01228-200

Country

Brazil

Facility Name

Novo Nordisk Investigational Site

City

Alexandria

ZIP/Postal Code

21131

Country

Egypt

Facility Name

Novo Nordisk Investigational Site

City

Cairo

ZIP/Postal Code

11562

Country

Egypt

Facility Name

Novo Nordisk Investigational Site

City

Cairo

ZIP/Postal Code

11591

Country

Egypt

Facility Name

Novo Nordisk Investigational Site

City

Gangwon-do

ZIP/Postal Code

26426

Country

Korea, Republic of

Facility Name

Novo Nordisk Investigational Site

City

Gyeonggi-do

ZIP/Postal Code

15355

Country

Korea, Republic of

Facility Name

Novo Nordisk Investigational Site

City

Pusan

ZIP/Postal Code

602-739

Country

Korea, Republic of

Facility Name

Novo Nordisk Investigational Site

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Novo Nordisk Investigational Site

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

Novo Nordisk Investigational Site

City

Seoul

ZIP/Postal Code

08308

Country

Korea, Republic of

Facility Name

Novo Nordisk Investigational Site

City

Suwon

ZIP/Postal Code

16499

Country

Korea, Republic of

Facility Name

Novo Nordisk Investigational Site

City

Hamar

ZIP/Postal Code

2317

Country

Norway

Facility Name

Novo Nordisk Investigational Site

City

Oslo

ZIP/Postal Code

0373

Country

Norway

Facility Name

Novo Nordisk Investigational Site

City

Oslo

ZIP/Postal Code

0586

Country

Norway

Facility Name

Novo Nordisk Investigational Site

City

Stavanger

ZIP/Postal Code

4011

Country

Norway

Facility Name

Novo Nordisk Investigational Site

City

Trondheim

ZIP/Postal Code

7027

Country

Norway

Facility Name

Novo Nordisk Investigational Site

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

Einsiedeln

ZIP/Postal Code

8840

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

Genève 14

ZIP/Postal Code

1211

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

Luzern 16

ZIP/Postal Code

6000

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

Olten

ZIP/Postal Code

4600

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

St. Gallen

ZIP/Postal Code

9007

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

St. Gallen

ZIP/Postal Code

9016

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

Winterthur

ZIP/Postal Code

8401

Country

Switzerland

Facility Name

Novo Nordisk Investigational Site

City

Adana

ZIP/Postal Code

01130

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Ankara

ZIP/Postal Code

06100

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Antalya

ZIP/Postal Code

07058

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34096

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34722

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34752

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34890

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34899

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Rize

ZIP/Postal Code

53020

Country

Turkey

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

According to Novo Nordisk disclosure commitment on novonordisk-trials.com

Citations:

PubMed Identifier

31189520

Citation

Pieber TR, Bode B, Mertens A, Cho YM, Christiansen E, Hertz CL, Wallenstein SOR, Buse JB; PIONEER 7 investigators. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019 Jul;7(7):528-539. doi: 10.1016/S2213-8587(19)30194-9. Epub 2019 Jun 9. Erratum In: Lancet Diabetes Endocrinol. 2019 Sep;7(9):e21.

Results Reference

result

PubMed Identifier

33318068

Citation

Buse JB, Bode BW, Mertens A, Cho YM, Christiansen E, Hertz CL, Nielsen MA, Pieber TR; PIONEER 7 investigators. Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial. BMJ Open Diabetes Res Care. 2020 Dec;8(2):e001649. doi: 10.1136/bmjdrc-2020-001649.

Results Reference

result

PubMed Identifier

35373893

Citation

Aroda VR, Bauer R, Christiansen E, Haluzik M, Kallenbach K, Montanya E, Rosenstock J, Meier JJ. Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Diabetes Obes Metab. 2022 Jul;24(7):1338-1350. doi: 10.1111/dom.14710. Epub 2022 May 9.

Results Reference

result

PubMed Identifier

33660198

Citation

Pratley RE, Crowley MJ, Gislum M, Hertz CL, Jensen TB, Khunti K, Mosenzon O, Buse JB. Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. Diabetes Ther. 2021 Apr;12(4):1099-1116. doi: 10.1007/s13300-020-00994-9. Epub 2021 Mar 4.

Results Reference

derived

PubMed Identifier

32998732

Citation

Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.

Results Reference

derived

PubMed Identifier

32267058

Citation

Thethi TK, Pratley R, Meier JJ. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes Metab. 2020 Aug;22(8):1263-1277. doi: 10.1111/dom.14054. Epub 2020 May 13.

Results Reference

derived

PubMed Identifier

31903692

Citation

Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.

Results Reference

derived

Links:

URL

http://novonordisk-trials.com

Description

Clinical Trials at Novo Nordisk

Learn more about this trial

Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.

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Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus. (PIONEER 7)

Diabetes, Diabetes Mellitus, Type 2

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial