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)

Novo Nordisk

Status and phase: Active, not recruiting; Phase 3

Conditions: Obesity; Diabetes Mellitus, Type 2

Treatments: Drug: Insuline glargine U100 (titrated); Drug: Insuline glargine U100 (reduced); Drug: Semaglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05514535

2021-004392-13 (EudraCT Number)

NN9535-4801

U1111-1267-0312 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 568 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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568 participants in 2 patient groups

Insuline glargine U100 (reduced) + semaglutide

Experimental group

Description:

Participants will initially receive 0.25 milligrams (mg) once-weekly semaglutide subcutaneously (s.c.) and the dose will be gradually escalated to 2 mg as an add-on to dose-reduced insulin glargine s.c. given once-daily. Insulin glargine U100 will be reduced by 10 U at the initiation of semaglutide and then again at each semaglutide dose escalation. Insulin glargine dose will be adjusted based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values (target SMPG: 4.4-7.2 millimoles per litre (mmol/L)).

Treatment:

Drug: Semaglutide

Drug: Insuline glargine U100 (reduced)

Insuline glargine U100 (titrated)

Active Comparator group

Description:

Participants will receive titrated insuline glargine U100 s.c. once-daily. Insulin glargine U100 dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).

Treatment:

Drug: Insuline glargine U100 (titrated)