Efficacy and Safety of Semaglutide Once-weekly Versus Exenatide ER 2.0 mg Once-weekly as add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects With Type 2 Diabetes

NCT01885208 | Completed Phase 3 Results

• 3 other identifiers: NN9535-36242012-004826-92U1111-1135-8647
• Study Type: interventional
• Target: 813
• Locations: 13 countries
• Sites: 146

Brief Summary

This trial is conducted in Europe and North and South America. The aim of the trial is to investigate the efficacy and safety of semaglutide once-weekly versus exenatide ER (extended release) 2.0 mg once-weekly as add-on to 1-2 oral antidiabetic drugs (OADs) in subjects with type 2 diabetes.

Conditions

Diabetes; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in HbA1c (Glycosylated Haemoglobin)

  Mean change in HbA1c from baseline to week 56.

  Week 0, week 56

Secondary Outcomes (5)

• Change From Baseline in Body Weight

  Week 0, week 56

• Change From Baseline in Fasting Plasma Glucose (FPG)

  Week 0, week 56

• Change From Baseline in Systolic and Diastolic Blood Pressure

  Week 0, week 56

• Change From Baseline in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs)

  Week 0, week 56

• Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target: (Yes/no)

  After 56 weeks' treatment

Study Arms (2)

Semaglutide 1.0 mg

EXPERIMENTAL

Drug: semaglutide

Exenatide ER 2.0 mg

ACTIVE COMPARATOR

Drug: exenatide

Interventions

semaglutide DRUG

One dose of 1.0 mg semaglutide administered subcutaneously (s.c., under the skin) once-weekly

Semaglutide 1.0 mg

exenatide DRUG

One dose of 2.0 mg exenatide ER administered subcutaneously (s.c., under the skin) once-weekly

Also known as: Bydureon®

Exenatide ER 2.0 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (146)

Novo Nordisk Investigational Site

Anniston, Alabama, 36207, United States

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Novo Nordisk Investigational Site

Birmingham, Alabama, 35216, United States

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Novo Nordisk Investigational Site

Pell City, Alabama, 35128, United States

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Novo Nordisk Investigational Site

Glendale, Arizona, 85306-4652, United States

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Mesa, Arizona, 85213, United States

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Phoenix, Arizona, 85027, United States

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Burbank, California, 91505, United States

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Hawaiian Gardens, California, 90716, United States

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Lomita, California, 90717, United States

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Los Angeles, California, 90017, United States

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Los Angeles, California, 90022, United States

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Los Angeles, California, 90057, United States

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Northridge, California, 91324, United States

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Northridge, California, 91325, United States

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San Diego, California, 92108, United States

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Tustin, California, 92780, United States

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Colorado Springs, Colorado, 80906, United States

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Colorado Springs, Colorado, 80909, United States

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Bradenton, Florida, 34201, United States

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Brandon, Florida, 33511, United States

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Coral Gables, Florida, 33134, United States

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Hialeah, Florida, 33012, United States

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Jacksonville, Florida, 32207, United States

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Miami, Florida, 33144, United States

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Miami, Florida, 33145, United States

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Miami, Florida, 33174, United States

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Miami Lakes, Florida, 33016, United States

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Plantation, Florida, 33324, United States

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Savannah, Georgia, 31406, United States

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Chicago, Illinois, 60634, United States

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Franklin, Indiana, 46131, United States

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Greenfield, Indiana, 46140, United States

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Muncie, Indiana, 47304, United States

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Louisville, Kentucky, 40213, United States

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Madisonville, Kentucky, 42431, United States

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Hyattsville, Maryland, 20782, United States

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Kalamazoo, Michigan, 49009, United States

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St Louis, Missouri, 63141, United States

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Las Vegas, Nevada, 89103, United States

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Mine Hill, New Jersey, 07803, United States

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Albuquerque, New Mexico, 87102, United States

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North Massapequa, New York, 11758-1802, United States

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Syracuse, New York, 13210, United States

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West Seneca, New York, 14224, United States

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Greensboro, North Carolina, 27408, United States

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Hickory, North Carolina, 28601, United States

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Whiteville, North Carolina, 28472, United States

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Akron, Ohio, 44311, United States

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Cincinnati, Ohio, 45255, United States

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Cleveland, Ohio, 44122, United States

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Delaware, Ohio, 43015, United States

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Corvallis, Oregon, 97330-3737, United States

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Portland, Oregon, 97210, United States

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Portland, Oregon, 97239, United States

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Lansdale, Pennsylvania, 19446-1002, United States

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Norristown, Pennsylvania, 19401, United States

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Charleston, South Carolina, 29407, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Murrells Inlet, South Carolina, 29576, United States

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Spartanburg, South Carolina, 29303, United States

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Chattanooga, Tennessee, 37404, United States

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Austin, Texas, 78731, United States

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Carrollton, Texas, 75010, United States

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Dallas, Texas, 75225, United States

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Dallas, Texas, 75390-8858, United States

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Fort Worth, Texas, 76117, United States

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Houston, Texas, 77008, United States

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Houston, Texas, 77024, United States

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Houston, Texas, 77040, United States

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Houston, Texas, 77072, United States

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Irving, Texas, 75039, United States

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Katy, Texas, 77450, United States

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San Antonio, Texas, 78245, United States

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Sugar Land, Texas, 77478, United States

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Sugar Land, Texas, 77479, United States

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Alexandria, Virginia, 22304, United States

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Buenos Aires, C1250AAN, Argentina

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Buenos Aires, C1425AGC, Argentina

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CABA, C1179AAB, Argentina

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Lanús Este, B1824KAJ, Argentina

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Mar del Plata, B7600GWV, Argentina

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Karlovac, 47000, Croatia

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Osijek, 31 000, Croatia

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Slavonski Brod, 35 000, Croatia

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Virovitica, 33000, Croatia

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Zagreb, 10 000, Croatia

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Helsinki, 00260, Finland

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Helsinki, FI-00100, Finland

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Kerava, FI-04200, Finland

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Oulu, 90220, Finland

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Turku, 20520, Finland

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Châlons-en-Champagne, 51005, France

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Corbeil-Essonnes, 91106, France

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La Rochelle, 17019, France

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Le Creusot, 71200, France

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Nanterre, 92014, France

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Roubaix, 59100, France

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Strasbourg, 67000, France

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Vénissieux, 69200, France

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Dresden, 01219, Germany

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Dresden, 01307, Germany

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Duisburg, 47051, Germany

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Hohenmölsen, 06679, Germany

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Mannheim, 68163, Germany

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Oldenburg, 23758, Germany

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Rehlingen-Siersburg, 66780, Germany

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Völklingen, 66333, Germany

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Athens, GR-12462, Greece

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Athens, GR-14233, Greece

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Athens, GR-17562, Greece

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Piraeus, GR-18536, Greece

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Thessaloniki, GR-54636, Greece

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Thessaloniki, GR-57010, Greece

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Bologna, 40138, Italy

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Città di Castello, 06012, Italy

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Milan, 20132, Italy

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Palermo, 90127, Italy

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Pavia, 27100, Italy

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Roma, 00161, Italy

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Siena, 53100, Italy

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Amsterdam, 1066 EC, Netherlands

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Apeldoorn, 7334 DZ, Netherlands

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Delft, 2625 AD, Netherlands

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Hoofddorp, 2134 TM, Netherlands

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Leeuwarden, 8934 AD, Netherlands

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Rotterdam, 3021 HC, Netherlands

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Rotterdam, 3039 BD, Netherlands

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Venlo, 5912 BL, Netherlands

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Zoetermeer, 2725 NA, Netherlands

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Caguas, 00725, Puerto Rico

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Manatí, 00674, Puerto Rico

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Belgrade, 11000, Serbia

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Belgrade, 11080, Serbia

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Kragujevac, 34000, Serbia

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Novi Sad, 21000, Serbia

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Basel, 4031, Switzerland

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Geneva, 1211, Switzerland

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Lucerne, 6000, Switzerland

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Sankt Gallen, 9007, Switzerland

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Zollikerberg, 8125, Switzerland

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Ayr, KA6 6DX, United Kingdom

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Bath, BA1 3NG, United Kingdom

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Bradford-on-Avon, BA15 1DQ, United Kingdom

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Haxey, DN9 2HY, United Kingdom

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Headington, OX3 7LE, United Kingdom

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Rotherham, S651DA, United Kingdom

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Related Publications (18)

• Fonseca VA, Capehorn MS, Garg SK, Jodar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide. J Clin Endocrinol Metab. 2019 Sep 1;104(9):4078-4086. doi: 10.1210/jc.2018-02685.

  PMID: 30938762 BACKGROUND

• Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=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.

  PMID: 30865526 BACKGROUND

• 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 Trial. Diabetes Care. 2018 Feb;41(2):258-266. doi: 10.2337/dc17-0417. Epub 2017 Dec 15.

  PMID: 29246950 RESULT

• Warren M, Chaykin L, Trachtenbarg D, Nayak G, Wijayasinghe N, Cariou B. Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2291-2297. doi: 10.1111/dom.13331. Epub 2018 Jun 7.

  PMID: 29687620 RESULT

• Petri KCC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. Diabetes Obes Metab. 2018 Sep;20(9):2238-2245. doi: 10.1111/dom.13358. Epub 2018 Jun 15.

  PMID: 29748996 RESULT

• Ahren B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.

  PMID: 29766634 RESULT

• DeVries JH, Desouza C, Bellary S, Unger J, Hansen OKH, Zacho J, Woo V. Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.

  PMID: 29862621 RESULT

• Carlsson Petri KC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Semaglutide s.c. Once-Weekly in Type 2 Diabetes: A Population Pharmacokinetic Analysis. Diabetes Ther. 2018 Aug;9(4):1533-1547. doi: 10.1007/s13300-018-0458-5. Epub 2018 Jun 15.

  PMID: 29907893 RESULT

• Malkin SJP, Russel-Szymczyk M, Liidemann G, Volke V, Hunt B. Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes: A Long-Term Cost-Effectiveness Analysis in Estonia. Diabetes Ther. 2019 Feb;10(1):159-176. doi: 10.1007/s13300-018-0542-x. Epub 2018 Dec 7.

  PMID: 30535837 RESULT

• Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar 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 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.

  PMID: 30615985 RESULT

• Overgaard RV, Lindberg SO, Thielke D. Impact on HbA1c and body weight of switching from other GLP-1 receptor agonists to semaglutide: A model-based approach. Diabetes Obes Metab. 2019 Jan;21(1):43-51. doi: 10.1111/dom.13479. Epub 2018 Aug 23.

  PMID: 30047216 RESULT

• Mosenzon O, Capehorn MS, De Remigis A, Rasmussen S, Weimers P, Rosenstock J. Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials. Cardiovasc Diabetol. 2022 Sep 2;21(1):172. doi: 10.1186/s12933-022-01585-7.

  PMID: 36056351 DERIVED

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

  PMID: 32998732 DERIVED

• 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.

  PMID: 32827435 DERIVED

• Capehorn M, Ghani Y, Hindsberger C, Johansen P, Jodar E. Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2-4 and 10. Diabetes Ther. 2020 May;11(5):1061-1075. doi: 10.1007/s13300-020-00796-z. Epub 2020 Mar 19.

  PMID: 32193837 DERIVED

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

  PMID: 31903692 DERIVED

• DeSouza C, Cariou B, Garg S, Lausvig N, Navarria A, Fonseca V. Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. J Clin Endocrinol Metab. 2020 Feb 1;105(2):dgz072. doi: 10.1210/clinem/dgz072.

  PMID: 31769496 DERIVED

• Jendle J, Birkenfeld AL, Polonsky WH, Silver R, Uusinarkaus K, Hansen T, Hakan-Bloch J, Tadayon S, Davies MJ. Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials. Diabetes Obes Metab. 2019 Oct;21(10):2315-2326. doi: 10.1111/dom.13816. Epub 2019 Jul 12.

  PMID: 31215727 DERIVED

Related Links

• Clinical Trials at Novo Nordisk

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Interventions

semaglutide; Exenatide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Clinical Reporting Anchor and Disclosure (1452)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

Study Officials

• Global Clinical Registry (GCR, 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: June 24, 2013
• Study Start: December 2, 2013
• Primary Completion: July 13, 2015
• Study Completion: July 13, 2015
• Last Updated: June 13, 2019
• Results First Posted: March 30, 2018

Record last verified: 2019-05

Locations

PR (2); FR (8); CH (5); GR (6); GB (6); AR (5); SE (4); FI (5); DE (8); CR (5); US (76); IT (7); NL (9)