Clinical trial NCT03136484: Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes
Official title: Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-05-02
Enrollment: 788
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Africa, Asia, Europe, North and South America. The aim of the trial is to compare the effect of once-weekly (OW) dosing of subcutaneous semaglutide (1.0 mg) versus once-daily dosing of oral canagliflozin (300 mg) on glycaemic control in subjects with type 2 diabetes (T2D) on a background treatment of metformin


Eligibility criteria: Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male or female, age equal to or above18 years at the time of signing informed consent - Diagnosed with type 2 diabetes mellitus (T2D) - HbA1c of 7.0-10.5% (53-91 mmol/mol, both inclusive) - Stable daily dose of metformin (equal to or above1500 mg or maximum tolerated dose as documented in the subject medical record and in compliance with current local label) for at least 90 days prior to the day of screening Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Previous participation in this trial. Participation is defined as signed informed consent - 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) - Participation in any clinical trial of an approved or non-approved investigational medicinal product within 90 days prior to the day of screening - Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol - Subject with alanine aminotransferase (ALT) above 2.5 x upper normal limit (UNL) - Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative - History or presence of pancreatitis (acute or chronic) - History of diabetic ketoacidosis (DKA) - Any of the following: myocardial infarction (MI), stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening - Subjects presently classified as being in New York Heart Association (NYHA) Class IV - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening - Renal impairment measured as eGFR below 60 ml/min/1.73 m\^2 as defined by Kidney Disease Improving global outcomes (KDIGO 2012) classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed - Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within the past 90 days prior to randomisation - Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed - Medical history of diabetes-related lower limb amputations or signs of critical lower limb ischemia, (e.g. skin ulcer, osteomyelitis, or gangrene) within the last 26 weeks prior to screening

Primary outcomes:
measure: Change in HbA1c
timeFrame: Week 0, week 52
Secondary outcomes:
measure: Change in Body Weight (kg)
timeFrame: Week 0, week 52
measure: Change in Total Fat Mass (kg)
timeFrame: Week 0, week 52
measure: Change in FPG (Fasting Plasma Glucose)
timeFrame: Week 0, week 52
measure: Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile
timeFrame: Week 0, week 52
measure: Change in SMPG- Mean Postprandial Increment Over All Meals
timeFrame: Week 0, week 52
measure: Change in Fasting Total Cholesterol
timeFrame: Week 0, week 52
measure: Change in Fasting LDL-cholesterol
timeFrame: Week 0, week 52
measure: Change in Fasting HDL-cholesterol
timeFrame: Week 0, week 52
measure: Change in Fasting Triglycerides
timeFrame: Week 0, week 52
measure: Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure)
timeFrame: Week 0, week 52
measure: Percentage Change in Body Weight (%)
timeFrame: Week 0, week 52
measure: Change in Body Mass Index (BMI)
timeFrame: Week 0, week 52
measure: Change in Waist Circumference
timeFrame: Week 0, week 52
measure: Percentage Change in Total Fat Mass (%)
timeFrame: Week 0, week 52
measure: Change in Total Lean Mass (kg)
timeFrame: Week 0, week 52
measure: Percentage Change in Total Lean Mass (%)
timeFrame: Week 0, week 52
measure: Change in Visceral Fat Mass (kg)
timeFrame: Week 0, week 52
measure: Percentage Change in Visceral Fat Mass (%)
timeFrame: Week 0, week 52
measure: Change in Ratio Between Total Fat Mass and Total Lean Mass
timeFrame: Week 0, week 52
measure: Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no)
timeFrame: Week 52
measure: Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
timeFrame: Week 52
measure: Participants Who Achieved HbA1c Reduction ≥1% (Yes/no)
timeFrame: Week 0, week 52
measure: Participants Who Achieved Weight Loss ≥3% (Yes/no)
timeFrame: Week 0, week 52
measure: Participants Who Achieved Weight Loss ≥5% (Yes/no)
timeFrame: Week 0, week 52
measure: Participants Who Achieved Weight Loss ≥10% (Yes/no)
timeFrame: Week 0, week 52
measure: Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no)
timeFrame: Week 0, week 52
measure: Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no)
timeFrame: Week 0, week 52
measure: Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no)
timeFrame: Week 0, week 52
measure: Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no)
timeFrame: Week 0, week 52
measure: Total Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Weeks 0-57
measure: Change in Haematological Parameter- Haemoglobin
timeFrame: Week 0, week 52
measure: Change in Haematological Parameter- Haematocrit
timeFrame: Week 0, week 52
measure: Change in Haematological Parameter- Erythrocytes
timeFrame: Week 0, week 52
measure: Change in Haematological Parameter- Leukocytes
timeFrame: Week 0, week 52
measure: Change in Haematological Parameter- Thrombocytes
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Amylase
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Lipase
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- ALT
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- AST
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- ALP
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Total Bilirubin
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Creatinine
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- eGFR
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Albumin
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Calcium
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Potassium
timeFrame: Week 0, week 52
measure: Change in Biochemistry Parameter- Sodium
timeFrame: Week 0, week 52
measure: Change in Calcitonin
timeFrame: Week 0, week 52
measure: Change in Pulse
timeFrame: Week 0, week 52
measure: Change in ECG
timeFrame: Week 0, week 52
measure: Change in Physical Examination
timeFrame: Week -2, week 52
measure: Eye Examination
timeFrame: Week 0, week 52
measure: Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-57
measure: Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-57
measure: Change in Short Form 36 Health Survey (SF-36): Sub-domains
timeFrame: Week 0, week 52
measure: Change in SF-36: Physical Component Summary (PCS)
timeFrame: Week 0, week 52
measure: Change in SF-36: Mental Component Summary (MCS)
timeFrame: Week 0, week 52
measure: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately
timeFrame: Week 0, week 52
measure: Change in Control of Eating Questionnaire (CoEQ): Domains
timeFrame: Week 0, week 52
measure: Change in CoEQ: Individual Items
timeFrame: Week 0, week 52
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: La Mesa
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Montclair
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Diego
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Spring Valley
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Tustin
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fleming Island
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Hallandale Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Hialeah
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facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Spring Hill
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Conyers
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Marietta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Meridian
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Council Bluffs
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Lake Charles
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Metairie
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Hyattsville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Detroit
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Flint
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Flint
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Sterling Heights
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Troy
country: United States
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state: Michigan
city: Trenton
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Brooklyn
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: New Windsor
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Greensboro
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Maumee
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Toledo
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Toledo
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Corvallis
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Anderson
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Amarillo
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Corpus Christi
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Corpus Christi
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Katy
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Splendora
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Saint George
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Herndon
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Olympia
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Wenatchee
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Rosario
country: Argentina
facility: Novo Nordisk Investigational Site
city: Salta
country: Argentina
facility: Novo Nordisk Investigational Site
city: Porto Alegre
country: Brazil
facility: Novo Nordisk Investigational Site
city: Rio de Janeiro
country: Brazil
facility: Novo Nordisk Investigational Site
city: Surrey
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: Brampton
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Burlington
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: London
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Pointe Claire
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Rohtak
country: India
facility: Novo Nordisk Investigational Site
state: Haryana
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Kochi
country: India
facility: Novo Nordisk Investigational Site
state: Kerala
city: Mumbai
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Nagpur
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Jaipur
country: India
facility: Novo Nordisk Investigational Site
state: Rajasthan
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Galway
country: Ireland
facility: Novo Nordisk Investigational Site
city: Mallow
country: Ireland
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Achrafieh
country: Lebanon
facility: Novo Nordisk Investigational Site
city: Hazmieh
country: Lebanon
facility: Novo Nordisk Investigational Site
city: Lebanon - Beirut
country: Lebanon
facility: Novo Nordisk Investigational Site
city: Mansourieh
country: Lebanon
facility: Novo Nordisk Investigational Site
city: Zgharta
country: Lebanon
facility: Novo Nordisk Investigational Site
city: Alor Gajah
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Ipoh
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Melaka
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Penang
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Sandakan
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Seremban
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Cuernavaca
country: Mexico
facility: Novo Nordisk Investigational Site
state: Morelos
city: Mexico City
country: Mexico
facility: Novo Nordisk Investigational Site
state: México, D.F.
city: Monterrey
country: Mexico
facility: Novo Nordisk Investigational Site
state: Nuevo León
city: Eksjö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Kristianstad
country: Sweden
facility: Novo Nordisk Investigational Site
city: Lund
country: Sweden
facility: Novo Nordisk Investigational Site
city: Malmö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Örebro
country: Sweden
facility: Novo Nordisk Investigational Site
city: Basingstoke
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bradford-on-Avon
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Dundee
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Haxey
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Nottingham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Plymouth
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Soham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Southampton
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Stevenage
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Torquay
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Wellingborough
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Lingvay I, Catarig AM, Frias JP, Kumar H, Lausvig NL, le Roux CW, Thielke D, Viljoen A, McCrimmon RJ. Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Nov;7(11):834-844. doi: 10.1016/S2213-8587(19)30311-0. Epub 2019 Sep 17.
citation: McCrimmon RJ, Catarig AM, Frias JP, Lausvig NL, le Roux CW, Thielke D, Lingvay I. Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial. Diabetologia. 2020 Mar;63(3):473-485. doi: 10.1007/s00125-019-05065-8. Epub 2020 Jan 2.
citation: Lingvay I, Capehorn MS, Catarig AM, Johansen P, Lawson J, Sandberg A, Shaw R, Paine A. Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis. J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4593-604. doi: 10.1210/clinem/dgaa577.