DiabetesPhase 3PIONEER 7NCT02849080
Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.
A Phase 3 study testing semaglutide and sitagliptin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 83 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes, Diabetes Mellitus, Type 2
- What is being tested?
- semaglutide and sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 504 participants
- Where
- 83 sitesin 10 countries
- Study dates
- 20 Sep 2016to 27 Mar 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
83 sites in 10 countries.
83 sites in 10 countries
United States37 sites
Novo Nordisk Investigational Site
Albuquerque, New Mexico, 87109-2134
Novo Nordisk Investigational Site
Atlanta, Georgia, 30318
Novo Nordisk Investigational Site
Billings, Montana, 59101
Novo Nordisk Investigational Site
Blackfoot, Idaho, 83221
Novo Nordisk Investigational Site
Boynton Beach, Florida, 33472
Novo Nordisk Investigational Site
Chapel Hill, North Carolina, 27514
Novo Nordisk Investigational Site
Chesapeake, Virginia, 23321
Novo Nordisk Investigational Site
Cleveland, Ohio, 44122
Novo Nordisk Investigational Site
Corpus Christi, Texas, 78413
Novo Nordisk Investigational Site
Dallas, Texas, 75231
Novo Nordisk Investigational Site
Evanston, Illinois, 60201-2477
Novo Nordisk Investigational Site
Flint, Michigan, 48504
Novo Nordisk Investigational Site
Glendale, Arizona, 85306-4652
Novo Nordisk Investigational Site
Greenfield, Indiana, 46140
Novo Nordisk Investigational Site
Greensboro, North Carolina, 27408
Novo Nordisk Investigational Site
Greenville, North Carolina, 27834
Novo Nordisk Investigational Site
Henderson, Nevada, 89052-2649
Novo Nordisk Investigational Site
Kingsport, Tennessee, 37660
Novo Nordisk Investigational Site
Lake Worth, Florida, 33461
Novo Nordisk Investigational Site
Lancaster, California, 93534
Novo Nordisk Investigational Site
Louisville, Kentucky, 40213
Novo Nordisk Investigational Site
Mentor, Ohio, 44060
Novo Nordisk Investigational Site
Metairie, Louisiana, 70002
Novo Nordisk Investigational Site
Miami Lakes, Florida, 33014
Novo Nordisk Investigational Site
Muncie, Indiana, 47304
Novo Nordisk Investigational Site
Murrells Inlet, South Carolina, 29576
Novo Nordisk Investigational Site
Myrtle Beach, South Carolina, 29572
Novo Nordisk Investigational Site
Oxon Hill, Maryland, 20745
Novo Nordisk Investigational Site
Phoenix, Arizona, 85050
Novo Nordisk Investigational Site
Pittsburgh, Pennsylvania, 15236
Novo Nordisk Investigational Site
Port Orange, Florida, 32127
Novo Nordisk Investigational Site
Renton, Washington, 98057
Novo Nordisk Investigational Site
Tampa, Florida, 33607
Novo Nordisk Investigational Site
Tampa, Florida, 33614
Novo Nordisk Investigational Site
Wadsworth, Ohio, 44281
Novo Nordisk Investigational Site
West Hills, California, 91304
Novo Nordisk Investigational Site
Whiteville, North Carolina, 28472
Turkey (Türkiye)9 sites
Novo Nordisk Investigational Site
Adana, 01130
Novo Nordisk Investigational Site
Ankara, 06100
Novo Nordisk Investigational Site
Antalya, 07058
Novo Nordisk Investigational Site
Istanbul, 34096
Novo Nordisk Investigational Site
Istanbul, 34722
Novo Nordisk Investigational Site
Istanbul, 34752
Novo Nordisk Investigational Site
Istanbul, 34890
Novo Nordisk Investigational Site
Istanbul, 34899
Novo Nordisk Investigational Site
Rize, 53020
Switzerland8 sites
Novo Nordisk Investigational Site
Bern, 3010
Novo Nordisk Investigational Site
Einsiedeln, 8840
Novo Nordisk Investigational Site
Geneva, 1211
Novo Nordisk Investigational Site
Lucerne, 6000
Novo Nordisk Investigational Site
Olten, 4600
Novo Nordisk Investigational Site
Sankt Gallen, 9007
Novo Nordisk Investigational Site
Sankt Gallen, 9016
Novo Nordisk Investigational Site
Winterthur, 8401
Belgium7 sites
Novo Nordisk Investigational Site
Bonheiden, 2820
Novo Nordisk Investigational Site
Boussu, 7300
Novo Nordisk Investigational Site
Brussels, 1200
Novo Nordisk Investigational Site
Edegem, 2650
Novo Nordisk Investigational Site
Ghent, 9000
Novo Nordisk Investigational Site
Leuven, 3000
Novo Nordisk Investigational Site
Liège, 4000
South Korea7 sites
Novo Nordisk Investigational Site
Gangwon-do, 26426
Novo Nordisk Investigational Site
Gyeonggi-do, 15355
Novo Nordisk Investigational Site
Pusan, 602-739
Novo Nordisk Investigational Site
Seoul, 03080
Novo Nordisk Investigational Site
Seoul, 03722
Novo Nordisk Investigational Site
Seoul, 08308
Novo Nordisk Investigational Site
Suwon, 16499
Norway5 sites
Novo Nordisk Investigational Site
Hamar, 2317
Novo Nordisk Investigational Site
Oslo, 0373
Novo Nordisk Investigational Site
Oslo, 0586
Novo Nordisk Investigational Site
Stavanger, 4011
Novo Nordisk Investigational Site
Trondheim, 7027
Argentina3 sites
Novo Nordisk Investigational Site
CABA, C1180AAX
Novo Nordisk Investigational Site
Corrientes, 3400
Novo Nordisk Investigational Site
Rosario, S2000DNM
Austria3 sites
Novo Nordisk Investigational Site
Graz, 8036
Novo Nordisk Investigational Site
Saint Stefan, 8511
Novo Nordisk Investigational Site
Vienna, 1130
Egypt3 sites
Novo Nordisk Investigational Site
Alexandria, 21131
Novo Nordisk Investigational Site
Cairo, 11562
Novo Nordisk Investigational Site
Cairo, 11591
About this study
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
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.
- Conditions
- Diabetes, Diabetes Mellitus, Type 2
- Being tested
- semaglutide, sitagliptin
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
semaglutideDrug
Oral administration once-daily.
sitagliptinDrug
Oral administration once-daily.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide flexible dosing (3, 7 or 14 mg) | Experimental | Not described Receives: Drug: semaglutide |
| Sitagliptin 100 mg | Active comparator | Not described Receives: Drug: sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 52
Secondary outcomes (68)
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.
Measured: Week 0, week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, Week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, Week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, Week 52
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.
Measured: Week 52
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.
Measured: Week 52
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.
Measured: Week 52
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.
Measured: Week 52
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.
Measured: Week 52
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.
Measured: Weeks 0-52
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.
Measured: Weeks 0-52
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.
Measured: Week 0-57
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.
Measured: Week 0-57
Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)
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.
Measured: Week 0-57
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.
Measured: Week 0, Week 52
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.
Measured: Week 0, Week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 0, week 52
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.
Measured: Week 52, week 104
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.
Measured: Week 52, week 104
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.
Measured: Week 52, week 104
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.
Measured: Week 52, week 104
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.
Measured: Week 52, Week 104
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.
Measured: Week 52, week 104
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.
Measured: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
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.
Measured: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
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.
Measured: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
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.
Measured: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
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.
Measured: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
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.
Measured: Weeks 53-104
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.
Measured: Weeks 53-104
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.
Measured: Week 53-109
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.
Measured: Week 52, Week 104
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.
Measured: Week 52, Week 104
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.
Measured: Week 52, week 104
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.
Measured: Week 52, week 104
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.
Measured: Week 53-109
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.
Measured: Week 53-109
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.
Measured: Week 52, week 104
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.
Measured: Week 52, week 104
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.
Measured: Week 0, week 104
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.
Measured: Week 0, week 104
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.
Measured: Week 0, week 104
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.
Measured: Week 0, week 104
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.
Measured: Week 0, Week 104
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.
Measured: Week 0, week 104
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.
Measured: Week 104
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.
Measured: Week 104
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.
Measured: Week 104
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.
Measured: Week 104
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.
Measured: Week 104
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.
Measured: Week 0-109
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.
Measured: Week 0, week 104
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.
Measured: Week 0, Week 104
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.
Measured: Week 0, week 104
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.
Measured: Week 0, week 104
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.
Measured: Week 0-109
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.
Measured: Week 0-109
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.
Measured: Week 0, week 104
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.
Measured: Week 0, week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2016 (estimated)
- Study start20 Sep 2016
- Primary completion28 Feb 2018
- Study completion27 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 504 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02849080
- Sponsor's protocol ID
- NN9924-4257
- Other IDs
- 2015-005593-38, U1111-1177-5103, 2015
- Acronym
- PIONEER 7
- Status last verified
- Jul 2022
- First submitted
- 21 Jul 2016
- Last updated
- 20 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
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.
PubMed 31189520Buse 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.
PubMed 33318068Aroda 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.
PubMed 35373893Pratley 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.
PubMed 33660198Husain 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.
PubMed 32998732Thethi 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.
PubMed 32267058Husain 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.
PubMed 31903692
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02849080
- Acronym / sponsor ID
- PIONEER 7 / NN9924-4257
- Conditions
- Diabetes, Diabetes Mellitus, Type 2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 504 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 20 Sep 2016 (actual)
- Primary completion
- 28 Feb 2018 (actual)
- Study completion
- 27 Mar 2019 (actual)
- First posted
- 29 Jul 2016 (estimated)
- Results
- Posted 17 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide flexible dosing (3, 7 or 14 mg) | Experimental | Drug: semaglutide |
| Sitagliptin 100 mg | Active comparator | Drug: sitagliptin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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)
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| semaglutideOral administration once-daily. | Drug | Semaglutide flexible dosing (3, 7 or 14 mg) |
| sitagliptinOral administration once-daily. | Drug | Sitagliptin 100 mg |
Primary outcome
Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)
Time frame: Week 52
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.
68 secondary outcomes
Change in Body Weight
Time frame: Week 0, week 52
Change in HbA1c
Time frame: Week 0, week 52
Change in FPG
Time frame: Week 0, week 52
Change in Body Weight (%)
Time frame: Week 0, week 52
Change in BMI
Time frame: Week 0, Week 52
Change in Waist Circumference
Time frame: Week 0, week 52
Change in Total Cholesterol (Ratio to Baseline)
Time frame: Week 0, Week 52
Change in LDL Cholesterol (Ratio to Baseline)
Time frame: Week 0, week 52
Change in HDL Cholesterol (Ratio to Baseline)
Time frame: Week 0, week 52
Change in Triglycerides (Ratio to Baseline)
Time frame: Week 0, week 52
Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)
Time frame: Week 0, week 52
Change in DTSQ
Time frame: Week 0, Week 52
Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)
Time frame: Week 52
Participants Who Achieve Weight Loss ≥5% (Yes/no)
Time frame: Week 52
Participants Who Achieve Weight Loss ≥10% (Yes/no)
Time frame: Week 52
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)
Time frame: Week 52
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)
Time frame: Week 52
Time to Rescue Medication
Time frame: Weeks 0-52
Time to Additional Anti-diabetic Medication
Time frame: Weeks 0-52
Number of TEAEs During Exposure to Trial Product
Time frame: Week 0-57
Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
Time frame: Week 0-57
Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)
Time frame: Week 0-57
Change in Amylase (Ratio to Baseline)
Time frame: Week 0, Week 52
Change in Lipase (Ratio to Baseline)
Time frame: Week 0, Week 52
Change in Pulse Rate
Time frame: Week 0, week 52
Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Time frame: Week 0, week 52
Change in HbA1c- Switch
Time frame: Week 52, week 104
Change in Body Weight- Switch
Time frame: Week 52, week 104
Change in Body Weight (%)- Switch
Time frame: Week 52, week 104
Change in FPG- Switch
Time frame: Week 52, week 104
Change in BMI- Switch
Time frame: Week 52, Week 104
Change in Waist Circumference- Switch
Time frame: Week 52, week 104
Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Switch
Time frame: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)- Switch
Time frame: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Participants Who Achieve Weight Loss ≥5% (Yes/no)- Switch
Time frame: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Switch
Time frame: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target and no Need for Rescue Medication (Yes/no)- Switch
Time frame: Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Time to Additional Anti-diabetic Medication- Switch
Time frame: Weeks 53-104
Time to Rescue Medication- Switch
Time frame: Weeks 53-104
Number of TEAEs During Exposure to Trial Product- Switch
Time frame: Week 53-109
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31189520Pieber 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.
- Results publication: PubMed 33318068Buse 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 publication: PubMed 35373893Aroda 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.
- Derived from this study: PubMed 33660198Pratley 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.
- Derived from this study: PubMed 32998732Husain 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.
- Derived from this study: PubMed 32267058Thethi 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.
- Derived from this study: PubMed 31903692Husain 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.
- Clinical Trials at Novo NordiskLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. According to Novo Nordisk disclosure commitment on novonordisk-trials.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
83 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing semaglutide and sitagliptin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 83 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 83 sites in United States, Turkey (Türkiye), Switzerland, Belgium, South Korea and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no) (time frame: Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02849080, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2022.