Efficacy and Safety of Semaglutide Versus Dulaglutide as add-on to Metformin in Subjects With Type 2 Diabetes.

Diabetes Mellitus, Type 2 Clinical Trial

— SUSTAIN 7  

Official title:

Efficacy and Safety of Semaglutide Versus Dulaglutide as add-on to Metformin in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02648204
• Other study ID #: NN9535-4216
• Secondary ID: 2014-005375-91U1
• Status: Completed
• Phase: Phase 3
• Start date: January 6, 2016
• Est. completion date: May 19, 2017

Study information

• Verified date: October 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Asia, Europe and the United States of America (USA). The aim of the trial is to investigate efficacy and safety of semaglutide versus dulaglutide as add-on to metformin in subjects with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1201
• Est. completion date: May 19, 2017
• Est. primary completion date: April 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: - Male or female, age at least 18 years at the time of signing informed consent. - HbA1c (glycosylated haemoglobin) 7.0 - 10.5% (53 - 91 mmol/mol) (both inclusive)

• Subjects on stable diabetes treatment with metformin (minimum of 1500 mg/day or maximal tolerated dose documented in the patient medical record) for 90 days prior to screening Exclusion Criteria: - 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 measures as required by local regulation or practice) - Any condition, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol - 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 screening. An exception is short-term insulin treatment for acute illness for a total of equal to or below 14 days
• History of pancreatitis (acute or chronic) - Screening calcitonin equal to or above 50 ng/L - Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma - Renal impairment defined as eGFR (electronic case report form) below 60 mL/min/1.73 m^2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) - Subjects presently classified as being in New York Heart Association Class IV - Planned coronary, carotid or peripheral artery revascularisation on the day of screening - Proliferative retinopathy or maculopathy requiring acute treatment - History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas) - Anticipated initiation or change in concomitant medications (for more than 14 consecutive days or on a frequent basis) known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids)

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
Administered subcutaneously (s.c., under the skin) once-weekly.
• Dulaglutide
Administered subcutaneously (s.c., under the skin) once-weekly.

Locations

Country	Name	City	State
Bulgaria	Novo Nordisk Investigational Site	Blagoevgrad
Bulgaria	Novo Nordisk Investigational Site	Burgas
Bulgaria	Novo Nordisk Investigational Site	Montana
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Stara Zagora
Croatia	Novo Nordisk Investigational Site	Karlovac
Croatia	Novo Nordisk Investigational Site	Krapinske Toplice
Croatia	Novo Nordisk Investigational Site	Rijeka
Croatia	Novo Nordisk Investigational Site	Varazdin
Croatia	Novo Nordisk Investigational Site	Virovitica
Croatia	Novo Nordisk Investigational Site	Zagreb
Finland	Novo Nordisk Investigational Site	Jyväskylä
Finland	Novo Nordisk Investigational Site	Kerava
Finland	Novo Nordisk Investigational Site	Kuusamo
Finland	Novo Nordisk Investigational Site	Raisio
Finland	Novo Nordisk Investigational Site	Tampere
Finland	Novo Nordisk Investigational Site	Turku
Germany	Novo Nordisk Investigational Site	Dresden
Germany	Novo Nordisk Investigational Site	Falkensee
Germany	Novo Nordisk Investigational Site	Friedrichsthal
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Rehlingen-Siersburg
Germany	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Chalkida, Evia
Greece	Novo Nordisk Investigational Site	Ioannina
Greece	Novo Nordisk Investigational Site	Piraeus
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Greece	Novo Nordisk Investigational Site	Thessaloniki
Hong Kong	Novo Nordisk Investigational Site	Shatin, New Territories
India	Novo Nordisk Investigational Site	Ahmedabad	Gujarat
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bhubaneswar	Orissa
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Delhi	New Delhi
India	Novo Nordisk Investigational Site	Goa	Maharashtra
India	Novo Nordisk Investigational Site	Guntur	Andhra Pradesh
India	Novo Nordisk Investigational Site	Guwahati	Assam
India	Novo Nordisk Investigational Site	Hyderabad
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Indore	Madhya Pradesh
India	Novo Nordisk Investigational Site	Kochi	Kerala
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kozhikode	Kerala
India	Novo Nordisk Investigational Site	Ludhiana
India	Novo Nordisk Investigational Site	Mohali	Punjab
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Dehli	New Delhi
India	Novo Nordisk Investigational Site	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Vellore	Tamil Nadu
India	Novo Nordisk Investigational Site	Visakhapatnam	Andhra Pradesh
Ireland	Novo Nordisk Investigational Site	Dublin
Ireland	Novo Nordisk Investigational Site	Dublin
Ireland	Novo Nordisk Investigational Site	Dublin
Ireland	Novo Nordisk Investigational Site	Galway
Ireland	Novo Nordisk Investigational Site	Gorey
Latvia	Novo Nordisk Investigational Site	Riga
Latvia	Novo Nordisk Investigational Site	Riga
Latvia	Novo Nordisk Investigational Site	Riga
Lithuania	Novo Nordisk Investigational Site	Kaunas
Lithuania	Novo Nordisk Investigational Site	Kaunas
Lithuania	Novo Nordisk Investigational Site	Panevezys
Lithuania	Novo Nordisk Investigational Site	Vilnius
Lithuania	Novo Nordisk Investigational Site	Vilnius
Portugal	Novo Nordisk Investigational Site	Almada
Portugal	Novo Nordisk Investigational Site	Aveiro
Portugal	Novo Nordisk Investigational Site	Lisboa
Portugal	Novo Nordisk Investigational Site	Tomar
Portugal	Novo Nordisk Investigational Site	Viana do Castelo
Portugal	Novo Nordisk Investigational Site	Vila Nova de Gaia
Puerto Rico	Novo Nordisk Investigational Site	Ponce
Romania	Novo Nordisk Investigational Site	Brasov
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Buzau
Romania	Novo Nordisk Investigational Site	Galati
Romania	Novo Nordisk Investigational Site	Oradea	Bihor
Romania	Novo Nordisk Investigational Site	Tirgu Mures	Mures
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Levice
Slovakia	Novo Nordisk Investigational Site	Piestany
Slovakia	Novo Nordisk Investigational Site	Poprad
Slovakia	Novo Nordisk Investigational Site	Prievidza
Spain	Novo Nordisk Investigational Site	Alicante
Spain	Novo Nordisk Investigational Site	La Roca del Vallés
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Málaga
Spain	Novo Nordisk Investigational Site	Palma de Mallorca
Spain	Novo Nordisk Investigational Site	Palma de Mallorca
Spain	Novo Nordisk Investigational Site	Segovia
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Vic (Barcelona)
United Kingdom	Novo Nordisk Investigational Site	Bradford-on-Avon
United Kingdom	Novo Nordisk Investigational Site	Northwood
United Kingdom	Novo Nordisk Investigational Site	Romford
United Kingdom	Novo Nordisk Investigational Site	Soham
United Kingdom	Novo Nordisk Investigational Site	Southampton
United Kingdom	Novo Nordisk Investigational Site	Southampton
United Kingdom	Novo Nordisk Investigational Site	Stevenage
United Kingdom	Novo Nordisk Investigational Site	Watford
United States	Novo Nordisk Investigational Site	Adairsville	Georgia
United States	Novo Nordisk Investigational Site	Addison	Illinois
United States	Novo Nordisk Investigational Site	Anaheim	California
United States	Novo Nordisk Investigational Site	Arlington	Texas
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Avon	Indiana
United States	Novo Nordisk Investigational Site	Bainbridge	Georgia
United States	Novo Nordisk Investigational Site	Buena Park	California
United States	Novo Nordisk Investigational Site	Carlsbad	California
United States	Novo Nordisk Investigational Site	Chandler	Arizona
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Clearwater	Florida
United States	Novo Nordisk Investigational Site	Clearwater	Florida
United States	Novo Nordisk Investigational Site	Concord	California
United States	Novo Nordisk Investigational Site	Conyers	Georgia
United States	Novo Nordisk Investigational Site	Coral Gables	Florida
United States	Novo Nordisk Investigational Site	Corpus Christi	Texas
United States	Novo Nordisk Investigational Site	Corvallis	Oregon
United States	Novo Nordisk Investigational Site	Covington	Kentucky
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Denver	Colorado
United States	Novo Nordisk Investigational Site	Edgewater	Florida
United States	Novo Nordisk Investigational Site	Evansville	Indiana
United States	Novo Nordisk Investigational Site	Fleetwood	Pennsylvania
United States	Novo Nordisk Investigational Site	Fort Lauderdale	Florida
United States	Novo Nordisk Investigational Site	Garner	North Carolina
United States	Novo Nordisk Investigational Site	Gillespie	Illinois
United States	Novo Nordisk Investigational Site	Greenfield	Indiana
United States	Novo Nordisk Investigational Site	Greer	South Carolina
United States	Novo Nordisk Investigational Site	Gurnee	Illinois
United States	Novo Nordisk Investigational Site	Harleysville	Pennsylvania
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Humboldt	Tennessee
United States	Novo Nordisk Investigational Site	Huntington Park	California
United States	Novo Nordisk Investigational Site	Hyattsville	Maryland
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Katy	Texas
United States	Novo Nordisk Investigational Site	Kissimmee	Florida
United States	Novo Nordisk Investigational Site	Lincoln	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Louisville	Kentucky
United States	Novo Nordisk Investigational Site	Marietta	Georgia
United States	Novo Nordisk Investigational Site	Marietta	Georgia
United States	Novo Nordisk Investigational Site	Mason	Ohio
United States	Novo Nordisk Investigational Site	Meridian	Idaho
United States	Novo Nordisk Investigational Site	Methuen	Massachusetts
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Missoula	Montana
United States	Novo Nordisk Investigational Site	Moncks Corner	South Carolina
United States	Novo Nordisk Investigational Site	Montclair	California
United States	Novo Nordisk Investigational Site	Muncie	Indiana
United States	Novo Nordisk Investigational Site	New York	New York
United States	Novo Nordisk Investigational Site	Newton	Kansas
United States	Novo Nordisk Investigational Site	Norwalk	Connecticut
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Owensboro	Kentucky
United States	Novo Nordisk Investigational Site	Oxon Hill	Maryland
United States	Novo Nordisk Investigational Site	Park City	Kansas
United States	Novo Nordisk Investigational Site	Pembroke Pines	Florida
United States	Novo Nordisk Investigational Site	Peoria	Illinois
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania
United States	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania
United States	Novo Nordisk Investigational Site	Port Gibson	Mississippi
United States	Novo Nordisk Investigational Site	Port Orange	Florida
United States	Novo Nordisk Investigational Site	Poway	California
United States	Novo Nordisk Investigational Site	Rapid City	South Dakota
United States	Novo Nordisk Investigational Site	Riverside	California
United States	Novo Nordisk Investigational Site	Riverton	Utah
United States	Novo Nordisk Investigational Site	Rochester	Michigan
United States	Novo Nordisk Investigational Site	Saint George	Utah
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Diego	California
United States	Novo Nordisk Investigational Site	Spartanburg	South Carolina
United States	Novo Nordisk Investigational Site	Spokane	Washington
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Suwanee	Georgia
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Trenton	New Jersey
United States	Novo Nordisk Investigational Site	Tulsa	Oklahoma
United States	Novo Nordisk Investigational Site	Tuscumbia	Alabama
United States	Novo Nordisk Investigational Site	Tustin	California
United States	Novo Nordisk Investigational Site	Van Nuys	California
United States	Novo Nordisk Investigational Site	Wadsworth	Ohio
United States	Novo Nordisk Investigational Site	Walla Walla	Washington
United States	Novo Nordisk Investigational Site	Wenatchee	Washington
United States	Novo Nordisk Investigational Site	Whiteville	North Carolina
United States	Novo Nordisk Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  Finland,  Germany,  Greece,  Hong Kong,  India,  Ireland,  Latvia,  Lithuania,  Portugal,  Puerto Rico,  Romania,  Slovakia,  Spain,  United Kingdom, 

References & Publications (9)

Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, Holst AG, Annett MP, Aroda VR. Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical — View Citation

Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jódar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 tri — View Citation

Johansen P, Håkan-Bloch J, Liu AR, Bech PG, Persson S, Leiter LA. Cost Effectiveness of Once-Weekly Semaglutide Versus Once-Weekly Dulaglutide in the Treatment of Type 2 Diabetes in Canada. Pharmacoecon Open. 2019 Mar 29. doi: 10.1007/s41669-019-0131-6. [Epub ahead of print] — View Citation

Malkin SJP, Russel-Szymczyk M, Psota M, Hlavinkova L, Hunt B. The Management of Type 2 Diabetes with Once-Weekly Semaglutide Versus Dulaglutide: A Long-Term Cost-Effectiveness Analysis in Slovakia. Adv Ther. 2019 Aug;36(8):2034-2051. doi: 10.1007/s12325-019-00965-y. Epub 2019 Jun 5. — View Citation

Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A; SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes E — View Citation

Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA(1C) =1.0% AND WEIGHT =5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13. — View Citation

Sharma R, Wilkinson L, Vrazic H, Popoff E, Lopes S, Kanters S, Druyts E. Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review a — View Citation

Viljoen A, Hoxer CS, Johansen P, Malkin S, Hunt B, Bain SC. Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK. Diabetes Obes Metab. 2019 Mar;21(3):611-621. doi: — View Citation

Wilkinson L, Hunt B, Johansen P, Iyer NN, Dang-Tan T, Pollock RF. Cost of Achieving HbA1c Treatment Targets and Weight Loss Responses with Once-Weekly Semaglutide Versus Dulaglutide in the United States. Diabetes Ther. 2018 Jun;9(3):951-961. doi: 10.1007/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c	Results are based on HbA1c data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on-treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	Week 0, week 40
Secondary	Change in Body Weight (kg)	Results are based on body weight data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication.	Week 0, week 40
Secondary	Change in Fasting Plasma Glucose	Results are based on fasting plasma glucose data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication.	Week 0, week 40
Secondary	Change in Systolic and Diastolic Blood Pressure	Results are based on systolic and diastolic blood pressure data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication.	Week 0, week 40
Secondary	Change in Overall Scores for Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire	The questionnaire contains 8 items and evaluates subjects' diabetes treatment in terms of convenience, flexibility and general feelings towards treatment. The result presented is 'Treatment Satisfaction' summary score (sum of 6 of the 8 items). Response options: 6 (best case) to 0 (worst case). Total scores range: 0-36. Higher scores=higher satisfaction. Results are based on data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was period where subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This includes observations recorded at, or after the date of first dose of trial product and not after first occurrence of following: the end-date of the 'on-treatment' observation period or initiation of rescue medication	Week 0, week 40
Secondary	HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target	Percentage of subjects who achieved HbA1c target below or equal to 6.5% (48 mmol/mol) after 40 weeks of treatment. Results are based on data from on-treatment without rescue medication period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	After 40 weeks treatment
Secondary	Change From Baseline in 7-point Self-measured Plasma Glucose (SMPG) Mean Profile	SMPG values were recorded at 7 time-points: before and 90 minutes after start of breakfast, lunch, and dinner, and at bedtime. Reported results are mean profile from on-treatment without rescue medication observation period. The 'on-treatment' observation period was period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	Week 0, week 40
Secondary	Change From Baseline 7-point Self-measured Plasma Glucose Increment	SMPG values were recorded at 7 time-points: before and 90 minutes after start of breakfast, lunch, and dinner, and at bedtime. Reported results are plasma glucose incremental profile from on-treatment without rescue medication observation period. The 'on-treatment' observation period was period where subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes observations recorded at, or after date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit	Week 0, week 40
Secondary	Change in Fasting Blood Lipids (Total Cholesterol)	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Change from baseline is presented in terms of ratio to baseline value.	Week 0, week 40
Secondary	Change in Fasting Blood Lipids (Low Density Lipoprotein [LDL] Cholesterol)	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Change from baseline is presented in terms of ratio to baseline value.	Week 0, week 40
Secondary	Change in Fasting Blood Lipids (High Density Lipoprotein [HDL] Cholesterol)	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Change from baseline is presented in terms of ratio to baseline value.	Week 0, week 40
Secondary	Change in Fasting Blood Lipids (Triglycerides)	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Change from baseline is presented in terms of ratio to baseline value.	Week 0, week 40
Secondary	Change in Body Mass Index (BMI)	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	Week 0, week 40
Secondary	Change in Waist Circumference	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	Week 0, week 40
Secondary	Change in Short Form Health Survey (SF-36v2™)	The questionnaire contains 36 items across 8 domains and 2 summary scores. Score range: 0 (worst score) to 100 (best score). Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was period where subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	Week 0, week 40
Secondary	Subjects Who After 40 Weeks Treatment Achieve (Yes/no) HbA1c <7.0% (53 mmol/Mol) American Diabetes Association (ADA) Target	Percentage of subjects who achieved HbA1c target below or equal to <7.0% (53 mmol/mol) after 40 weeks of treatment. Results are based on data from on-treatment without rescue medication period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	After 40 weeks of treatment
Secondary	Subjects Who After 40 Weeks Treatment Achieve (Yes/no) Weight Loss =5%	Percentage of subjects who achieved weight loss =5% after 40 weeks of treatment. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	After 40 weeks treatment
Secondary	Subjects Who After 40 Weeks Treatment Achieve (Yes/no) Weight Loss =10%	Percentage of subjects who achieved weight loss =10% after 40 weeks of treatment. Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	After 40 weeks treatment
Secondary	Subjects Who After 40 Weeks Treatment Achieve (Yes/no) HbA1c <7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain	Percentage of subjects achieved (yes/no) HbA1c <7.0% (53 mmol/mol) without severe or BG confirmed symptomatic hypoglycaemia episodes and no weight gain after 40 weeks of treatment. Results are based on data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was period where subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was subset of 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit	After 40 weeks of treatment
Secondary	Subjects Who After 40 Weeks Treatment Achieve (Yes/no) HbA1c Reduction =1%	Percentage of subjects who achieved (yes/no) HbA1c reduction of =1% after 40 weeks of treatment. Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	After 40 weeks of treatment
Secondary	Subjects Who After 40 Weeks Treatment Achieve (Yes/no) Weight Loss =3%	Percentage of subjects who achieved (yes/no) weight loss of =3% after 40 weeks of treatment. Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	After 40 weeks treatment
Secondary	Subjects Who After 40 Weeks Treatment Achieve (Yes/no) HbA1c Reduction =1% and Weight Loss =3%	Percentage of subjects who achieved (yes/no) HbA1c reduction =1% and weight loss =3% 40 weeks of treatment. Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. Missing data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	After 40 weeks treatment
Secondary	Number of Treatment Emergent Adverse Events (TEAEs)	A TEAE was defined as an AE with onset in the 'on-treatment' period (information collected while subjects were considered as exposed to trial product). This corresponded to information collected until the follow-up (5 weeks after the last treatment including a visit window of +7 days).	40 weeks + follow-up of 5 weeks
Secondary	Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemia Episodes	A treatment emergent hypoglycaemic episode was defined as an episode with onset in the 'on-treatment' period (information collected while subjects were considered as exposed to trial product). This corresponded to information collected until the follow-up (5 weeks after the last treatment including a visit window of +7 days). Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode that was severe according to the American Diabetes Association classification or BG-confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.	40 weeks + follow-up of 5 weeks
Secondary	Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	Percentage of subjects with treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes. A treatment emergent hypoglycaemic episode was defined as an episode with onset in the 'on-treatment' period (information collected while subjects were considered as exposed to trial product). This corresponded to information collected until the follow-up (5 weeks after the last treatment including a visit window of +7 days). Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode that was severe according to the American Diabetes Association classification or BG-confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.	40 weeks + follow-up of 5 weeks
Secondary	Change in Amylase	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Change from baseline is presented in terms of ratio to baseline value.	Week 0, week 40
Secondary	Change in Lipase	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Change from baseline is presented in terms of ratio to baseline value.	Week 0, week 40
Secondary	Change in Pulse Rate	Results are based on the data from on-treatment without rescue medication observation period. The 'on-treatment' observation period was the period where the subject was considered to be exposed to trial product. The 'on-treatment without rescue medication' observation period was a subset of the 'on -treatment' observation period, where subjects did not receive any non-investigational antidiabetic medication (rescue medication). This period includes the observations recorded at, or after the date of first dose of trial product and not after the first occurrence of the following: the end-date of the 'on-treatment' observation period or initiation of rescue medication. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.	Week 0, week 40

External Links

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