A Research Study to Look Into How Semaglutide, Together With a Lower Dose of Insulin Glargine, Compares to a Higher Dose of Insulin Glargine Alone in People With Type 2 Diabetes (SUSTAIN OPTIMIZE)

Obesity Clinical Trial

Official title:

Efficacy and Safety of Once-weekly Semaglutide S.C. 2.0 mg as Add-on to Dose-reduced Insulin Glargine vs Titrated Insulin Glargine in Participants With Type 2 Diabetes and Overweight

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05514535
• Other study ID #: NN9535-4801
• Secondary ID: U1111-1267-03122
• Status: Recruiting
• Phase: Phase 3
• Start date: August 29, 2022
• Est. completion date: July 2, 2025

Study information

• Verified date: June 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study compares semaglutide, together with a lower dose of insulin glargine, to a higher dose of insulin glargine in participants with type 2 diabetes. The study looks at how well the study medicines control blood glucose levels. Participants will either get semaglutide together with a lower dose of insulin glargine or a higher dose of insulin glargine. The study will last for about 47 weeks (approximately 11 months). Participants will have 9 clinic visits, 15 phone/video calls and 1 home visit. Participants will be asked to wear a sensor that measures their blood sugar all the time in 2 periods of 10 days during the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 568
• Est. completion date: July 2, 2025
• Est. primary completion date: May 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with Type 2 Diabetes Mellitus (T2D) mellitus greater than or equal to (>=) 180 days before screening.

• Glycated haemoglobin (HbA1c) of 7-10 percentage [(53-86 millimoles per mole (mmol/mol)] (both inclusive) as assessed by central laboratory on the day of screening.

• Body mass index (BMI) greater than or equal to (>=) 25 kilograms per meter square (kg/m^2) on the day of screening.

• Stable daily dose(s) greater than or equal to (>=) 90 days before screening of any of the following anti-diabetic drugs or combination regimens:

• Any metformin formulations greater than or equal to (>=) 1500 milligrams (mg) or maximum tolerated or effective dose.

• Any metformin combination formulation greater than or equal to (>=) 1500 mg or maximum tolerated or effective dose.

The treatment can be with or without sodium glucose cotransporter 2 (SGLT-2) inhibitors.

• Treated with a once daily basal insulin (e.g. insulin glargine Unit 100 or U300, neutral protamine hagedorn (NPH) insulin, insulin detemir, insulin degludec) less than or equal to (<=) 40 units/day (U/day) for greater than or equal to (>=) 90 days before screening. Short-term bolus insulin treatment for a maximum of 14 days before screening is allowed.

Exclusion Criteria:

• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

• Potentially missed diagnosis of Type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA) verified by C-peptide less than 0.26 nanomoles per litre (nmol/L) (or 260 picomoles per liter [pmol/L] [0.78 nanograms per millilitre {ng/mL}]) or antibodies to glutamic acid decarboxylase (anti-GAD) greater than 5 units/millilitre, as measured by the central laboratory at screening.

• Presence or history of pancreatitis (acute or chronic).

• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 30 millilitre per minute per 1.73 meter square at screening as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification.

• Any episodes of diabetic ketoacidosis within 90 days before screening.

• Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity

Intervention

Drug:
• Semaglutide
Participants will receive once-weekly semaglutide s.c. for 40 weeks. Semaglutide 0.25 mg will be given at week 0 and then the dose will be escalated at weeks 4, 8 and 12 to 0.5 mg, 1 mg, 2 mg respectively.
• Insuline glargine U100 (reduced)
Participants will receive insulin glargine U100 s.c. once-daily. Insulin glargine dose will be reduced by 10 U at initiation of semaglutide and then again at each semaglutide dose escalation up to 40 weeks. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).
• Insuline glargine U100 (titrated)
Participants will receive titrated insulin glargine U100 s.c. once-daily up to 40 weeks. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).

Locations

Country	Name	City	State
Czechia	EDUMED s.r.o. Nachod	Nachod
Czechia	Diahelp - diabetologie	Pardubice 5
Czechia	MUDr. Jitka Zemanova diabetologie a interna	Plzen - Vychodni Predmesti
Czechia	Diabet2 s.r.o.	Praha 1
Czechia	MUDr. Michala Pelikanova	Praha 4
Czechia	MUDr. Michala Pelikanova	Praha 4
Czechia	ResTrial s.r.o.	Praha 8
Czechia	ResTrial s.r.o.	Praha 8
Greece	University Hospital of Alexandroupolis	Alexandroupolis
Greece	"Laiko" General Hospital of Athens	Athens
Greece	Alexandra General Hospital, Therapeutic Clinic	Athens
Greece	Alexandra General Hospital, Therapeutic Clinic	Athens
Greece	University Hospital of Athens ATTIKON	Haidari-Athens	Attica
Greece	General Hospital of Nikaia	Nikaia
Greece	Tzaneio General Hospital of Piraeus	Piraeus
Greece	"Thermi" Private Hosital	Thessaloniki
Greece	AHEPA General University Hospital	Thessaloniki
Greece	AHEPA General University Hospital	Thessaloniki
Greece	EUROMEDICA Gen Clinic The/ki, Endocrin,Metabolism,Diabetes	Thessaloniki
Greece	General Hospital of Thessaloniki "G.Papanikolaou"	Thessaloniki
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Policlinico Mater Domini Università di Catanzaro	Catanzaro
Italy	Ospedale Santa Maria Goretti - UOD Diabetologia	Latina	LT
Italy	Ospedale Civile Campo di Marte	Lucca	LU
Italy	Istituto Scientifico San Raffaele	Milano	MI
Italy	ASST degli Spedali Civili di Brescia-Presidio Ospedaliero di Montichiari	Montichiari
Italy	A.O.U. Università Studi della Campania "Luigi Vanvitelli"	Napoli
Italy	Azienda Ospedaliera di Perugia;Ospedale S. Maria della Miser	Perugia
Italy	Policlinico A. Gemelli	Rome
Portugal	Hospital Garcia de Orta	Almada
Portugal	Hospital Infante D. Pedro - Aveiro	Aveiro
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar do Oeste - Unidade Caldas de Rainha	Caldas da Rainha
Portugal	Centro Hospitalar de Leiria EPE - Hospital de Santo André	Leiria
Portugal	Centro Hospitalar Lisboa Central - Hospital Curry Cabral	Lisboa
Portugal	Centro Hospitalar Lisboa Ocidental	Lisboa
Portugal	Unidade Local de Saúde de Matosinhos	Matosinhos
Portugal	Unidade Local de Saúde do Alto Minho - Viana do Castelo	Viana do Castelo
Romania	CMI Dr Pop Lavinia	Baia Mare	Maramures
Romania	Clinica Grivitei 224 S.R.L.	Braila
Romania	Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed	Brasov
Romania	Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed	Brasov
Romania	Diabs&Nutricare Srl	Bucuresti
Romania	Clinic of Diabetes Constanta	Constanta
Romania	Clinic of Diabetes Constanta	Constanta
Romania	Clinical Emergency Sf. Apostol Andrei Hospital	Galati
Romania	SC Consultmed SRL	Iasi
Romania	Medical Practice SRL	Oradea
Romania	SC Grand Med SRL	Oradea	Bihor
Romania	Novus Medical Clinica SRL	Ploiesti	Prahova
Romania	S.C. Dianutrilife Medica S.R.L.	Ploiesti
Romania	Clinica Korall S.R.L. Satu Mare	Satu-Mare
Romania	Spitalul Judetean de Urgenta Targoviste	Targoviste	Dambovita
Romania	Dentosim Queen Srl	Targu Mures
Romania	Centrul Medical Sfantul Stefan	Timisoara	Timis
Slovakia	DIA - CLARUS s.r.o.	Bojnice
Slovakia	MEDISPEKTRUM s.r.o.	Bratislava
Slovakia	MediTask, s.r.o	Bratislava
Slovakia	Diabetologicka ambulancia DIA-MAX s.r.o.	Levice
Slovakia	IN-DIA s.r.o.	Lucenec
Slovakia	FUNKYSTUFF s.r.o	Nove Zamky
Slovakia	Diakom, spol. s r.o.	Poprad
Slovakia	DIALIPID, s.r.o.	Presov
Slovakia	Tatratrial s.r.o.	Roznava
Slovakia	BENROD s.r.o.	Sturovo
South Africa	Diabetes Care Centre & CDE Centre	Benoni	Gauteng
South Africa	Dr J Reddy	Durban	KwaZulu-Natal
South Africa	Dr Pillay's Rooms	Durban	KwaZulu-Natal
South Africa	Dr Pillay's Rooms	Durban	KwaZulu-Natal
South Africa	Centre for Diabetes	Johannesburg	Gauteng
South Africa	East Rand Physicians	Johannesburg	Gauteng
South Africa	Dr T Padayachee	Umkomaas	KwaZulu-Natal
Spain	Centro Periférico de Especialidades Bola Azul	Almeria
Spain	ABS La Roca del Vallés	La Roca del Vallés
Spain	Hospital Infanta Leonor	Madrid
Spain	Hospital Son Espases	Palma de Mallorca
Spain	Hospital Infanta Luisa	Sevilla
Ukraine	?ommunal non-profit enterprise Regional Clinical Hospital	Kharkiv
Ukraine	CNI "Khmelnytskyi regional hospital" of KRC	Khmelnytskyi
Ukraine	Ternopil Central District Hospital	Ternopil
Ukraine	Medical centre"Elitmedservis"LLC	Zaporizhzhia
United States	Albany Medical College - Endo	Albany	New York
United States	Amarillo Med Spec LLP	Amarillo	Texas
United States	Arlington Family Res. Ctr Inc	Arlington	Texas
United States	CVS Store Number: 7689	Atlanta	Georgia
United States	Velocity Clin Res Cleveland	Beachwood	Ohio
United States	Joslin Center For Diabetes	Boston	Massachusetts
United States	Northern Pines Hlth Ctr, PC	Buckley	Michigan
United States	Mercury Str Med Grp, PLLC	Butte	Montana
United States	Diab & Endo Assoc of Stark Co	Canton	Ohio
United States	Diab & Endo Assoc of Stark Co	Canton	Ohio
United States	Chattanooga Medical Research, LLC	Chattanooga	Tennessee
United States	Virginia Endo Res, LLC	Chesapeake	Virginia
United States	Cedar-Crosse Research Center	Chicago	Illinois
United States	John Muir Physicians Network	Concord	California
United States	West Broadway Clinic	Council Bluffs	Iowa
United States	Thyroid Endocrinology & Diabetes PA	Dallas	Texas
United States	Velocity Clinical Res-Dallas	Dallas	Texas
United States	Lillestol Research LLC	Fargo	North Dakota
United States	Elite Research Center	Flint	Michigan
United States	Diabetes and Thyroid Ctr of FW	Fort Worth	Texas
United States	Valley Research	Fresno	California
United States	St. Jos Heritage Hlthcr_Fllrtn	Fullerton	California
United States	Lenzmeier Fam Med CCT Research	Glendale	Arizona
United States	Coastal Heritage Clinical Research	Hinesville	Georgia
United States	Encore Medical Research LLC	Hollywood	Florida
United States	Velocity Clin Res Hunt Park	Huntington Park	California
United States	MedStar Hlth Res Institute	Hyattsville	Maryland
United States	Compass Point Research	Indianapolis	Indiana
United States	Jacksonville Ctr For Clin Res	Jacksonville	Florida
United States	Northeast Res Inst. Inc.	Jacksonville	Florida
United States	Holston Medical Group	Kingsport	Tennessee
United States	Accellacare._TN	Knoxville	Tennessee
United States	Velocity Clin Res San Diego	La Mesa	California
United States	First Valley Medical Group	Lancaster	California
United States	Palm Research Center Inc-Vegas	Las Vegas	Nevada
United States	The Research Group of Lexington LLC	Lexington	Kentucky
United States	Loma Linda Univ Hlth Cr Endo	Loma Linda	California
United States	Downtown LA Res Ctr. Inc.	Los Angeles	California
United States	Velocity Clin Res Wstlke	Los Angeles	California
United States	Advanced Med Res Maumee	Maumee	Ohio
United States	Elite Research Center	Miami	Florida
United States	International Research Associates, LLC_Miami	Miami	Florida
United States	New Horizon Research Center	Miami	Florida
United States	Reyes Clinical Research, Inc	Miami	Florida
United States	Carteret Medical Group	Morehead City	North Carolina
United States	Lucas Research Inc.	Morehead City	North Carolina
United States	WVU Medicine	Morgantown	West Virginia
United States	Southern New Hampshire Diabete	Nashua	New Hampshire
United States	AMR New Orleans	New Orleans	Louisiana
United States	Suncoast Clin Res Port Richey	New Port Richey	Florida
United States	Suncoast Clinical Research, Inc._New Port Richey	New Port Richey	Florida
United States	Mid Hudson Med Res-New Windsor	New Windsor	New York
United States	Valley Clinical Trials, Inc.	Northridge	California
United States	Renstar Medical Research	Ocala	Florida
United States	Thomas Jefferson Univ Di Rsrch Ctr	Philadelphia	Pennsylvania
United States	CVS Store Number: 01396	Reston	Virginia
United States	CVS Store Number: 1537	Richmond	Virginia
United States	Endo And Metab Cons	Rockville	Maryland
United States	Endocrine Research Solutions	Roswell	Georgia
United States	Chrysalis Clinical Research	Saint George	Utah
United States	StudyMetrix Research LLC	Saint Peters	Missouri
United States	Olympus Family Medicine	Salt Lake City	Utah
United States	Diabetes Glandular Diseases Clinic	San Antonio	Texas
United States	Diabetes Glandular Diseases Clinic	San Antonio	Texas
United States	San Antonio Prem Int Med	San Antonio	Texas
United States	VIP Trials	San Antonio	Texas
United States	Wetlin Research Associates, Inc.	San Diego	California
United States	CVS Store Number: 05520	Savannah	Georgia
United States	Consano Clinical Research, LLC	Shavano Park	Texas
United States	Consano Clinical Research, LLC	Shavano Park	Texas
United States	Endo & Diab Care Assoc	Slidell	Louisiana
United States	University of Toledo_Toledo	Toledo	Ohio
United States	Cotton O'Neil Clin Research Ctr	Topeka	Kansas
United States	Arcturus Healthcare, PLC	Troy	Michigan
United States	Hillcrest Family Health Center	Waco	Texas
United States	Iowa Diab & Endo Res Center	West Des Moines	Iowa
United States	San Fernando Valley Hlth Inst	West Hills	California
United States	Amherst Family Practice P.C.	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Czechia,  Greece,  Italy,  Portugal,  Romania,  Slovakia,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycated Haemoglobin (HbA1c)	Non-inferiority of semaglutide s.c. as add-on to dose-reduced insulin glargine to that of titrated insulin glargine will be assessed based on the clinically acceptable margin of 0.3 percentage (%) for the mean treatment difference in HbA1c. Measured as percentage.	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Body Weight	Measured as kilogram	From baseline (week 0) to end of treatment (week 40)
Secondary	Relative Change in Daily Insulin Dose	Measured as percentage	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in HbA1c	Superiority of semaglutide s.c. as add-on to dose-reduced insulin glargine versus titrated insulin glargine will be assessed. Measured as percentage.	From baseline (week 0) to end of treatment (week 40)
Secondary	Score of Diabetes Treatment Satisfaction Questionnaire - Change Version (DTSQc)	The questionnaire has been designed to measure the change in the level of satisfaction with diabetes treatment regimens in participants with diabetes who have had a recent intervention. It consists of 8 questions, which are to be answered on a Likert scale from -3 to +3 (-3 = much less satisfied now to +3 = much more satisfied now), with 0 (midpoint), representing no change. Six questions are summed to produce a total treatment satisfaction score. The remaining two questions concern perceived frequency of hyperglycemia and perceived frequency of hypoglycemia, respectively. The DTSQc total treatment satisfaction score ranges from -18 to +18, with higher scores associated with greater treatment satisfaction. Measured as score on a scale.	At end of treatment (week 40)
Secondary	Participants Achieving: Insulin Dose Equal to 0 Units (Yes/No)	Measured as count of participants	At end of treatment (week 40)
Secondary	Participants Achieving: Insulin Dose Reduced From Baseline by at Least 50 Percentage (Yes/No)	Measured as count of participants	At end of treatment (week 40)
Secondary	Participants Achieving: HbA1c less than 7 Percentage (Yes/No)	Measured as count of participants	At end of treatment (week 40)
Secondary	Number of Severe Hypoglycaemic Episodes (Level 3)	Measured as number of episodes	From baseline (week 0) to end of treatment (week 40)
Secondary	Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 Millimoles Per Litre (mmol/L) [54 Milligrams Per Decilitre (mg/dL)] Confirmed by Blood Glucose Meter)	Measured as number of episodes	From baseline (week 0) to end of treatment (week 40)
Secondary	Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose Meter) or Severe Hypoglycaemic Episodes (Level 3)	Measured as number of episodes	From baseline (week 0) to end of treatment (week 40)
Secondary	Participants Achieving All of The Following Targets: HbA1c Reduced From Baseline by At Least 0.3 %; Insulin Dose Reduced From Baseline; No Hypoglycaemic Episodes; No Weight Gain	No hypoglycaemic episodes defined as less than 3.9 mmol/L [70 milligrams per decilitre (mg/dL)] confirmed by Blood Glucose meter. Outcome measure measured as count of participants.	At end of treatment (week 40)
Secondary	Change in Score of Diabetes Treatment Satisfaction Questionnaire - Status Version (DTSQs)	The questionnaire has been designed to measure satisfaction with diabetes treatment regimens in participants with diabetes. The questionnaire contains 8 components and measures the treatment for diabetes (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings regarding treatment. The value presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. Measured as score on a scale.	From baseline (week 0) to end of treatment (week 40)
Secondary	Change in Score of Short Form 36 Version 2 (SF-36 v2)	The SF-36 v2 will be used to measure differences in quality of life and mental wellbeing. The scores 0-100 (where higher scores indicated a better quality of life and mental wellbeing) from the SF-36 will be converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 United States general population. Measured as score on a scale.	From baseline (week 0) to end of treatment (week 40)