Glucagon-like Peptide-1 Agonism With Very Low Calorie Diets

NCT ID: NCT05606471

Last Updated: 2022-11-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-15
• Study Completion Date: 2023-07-28

Brief Summary

The very-low calorie diet (VLCD) is a highly effective and safe way to rapidly lose significant amounts of weight and dramatically improve blood sugar control in a short period of time (typically 8-12 weeks). It has recently become recommended by the UK National Health Service as a treatment for selected patients with type 2 diabetes. One drawback of VLCD however is the associated loss of skeletal muscle which affects some patients.

Semaglutide is a well-known medication for type 2 diabetes that also improves blood sugar control and facilitates weight loss. Recent research has shown that it may also stimulate muscle growth, meaning it could help to preserve muscle mass during weight loss. Therefore, this research study aims to see whether taking Semaglutide alongside the VLCD reduces the amount of muscle lost, and could improve the long-term outcomes of VLCD.

The study will take place in the Medical School building in the Royal Derby Hospital. Up to 45 participants will be recruited and allocated into one of 3 groups:

1. Semaglutide only

2. VLCD only

3. Combined Semaglutide plus VLCD The study is 12 weeks in duration and consists of four visits including two 6-hour visits, one 4-hour visit and one 30-minute visit. The first visit is a short Preliminary Visit where participants are asked to ingest stable isotope drinks for measurement of muscle growth rates and muscle mass. Food intake and physical activity monitoring will also be commenced.

Visits 1 & 3 are identical and occur at the beginning and end of the 12-week intervention period, respectively. During these visits participants will undergo a Dual-energy X-ray absorptiometry (DXA) scan, a right vastus lateralis muscle ultrasound scan & muscle biopsy, an intravenous glucose tolerance test, electromyography, tests of muscular function, gait & balance, and questionnaires regarding quality of life & physical activity. These visits are expected to last up to 6 hours.

Visit 2 is a shorter visit mid-way through the 12 weeks, lasting approximately 4.5 hours. Participants will undergo another DXA scan and muscle biopsy in addition to having multiple blood tests taken over a 4-hour period to determine muscle protein breakdown rates.

During the 12 weeks, those in the VLCD group will be asked to stick strictly to an 800 kilocalorie very-low calorie diet, whilst those in the Semaglutide group will be required to inject themselves with Semaglutide once a week. Those in the combined group will be asked to do both. All participants will be monitored closely throughout the 12-week period, with regular phone calls and/or emails.

Conditions

Type 2 Diabetes Mellitus in Obese

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VLCD only

Participants in this group will be placed on a very-low calorie diet with a daily energy intake limit of 800 kilocalories. 600 kilocalories will be made up of total meal replacement products supplied by Lighterlife UK. The remaining 200 kilocalories will be flexible for participants to add additional vegetables to supplement the total meal replacement products, allowing some variety to the diet.

Group Type: ACTIVE_COMPARATOR

Very-low Calorie Diet

Intervention Type: DIETARY_SUPPLEMENT

Total meal replacement with a limit of 800 kilocalories per day

Semaglutide only

Participants will be asked to self-administer the GLP-1 agonist Semaglutide weekly, as per clinical practice. They will be asked to start at 0.25mg and increase every two weeks (if tolerated) to the maintenance dose of 1mg, which they will continue until the end of the study.

Group Type: ACTIVE_COMPARATOR

Semaglutide Pen Injector [Ozempic]

Intervention Type: DRUG

Glucagon-like peptide 1 (GLP-1) receptor agonist

Combined VLCD plus Semaglutide

Participants in this group will both partake in the VLCD, and take the weekly dose of Semaglutide (as described above).

Group Type: EXPERIMENTAL

Semaglutide Pen Injector [Ozempic]

Intervention Type: DRUG

Glucagon-like peptide 1 (GLP-1) receptor agonist

Very-low Calorie Diet

Intervention Type: DIETARY_SUPPLEMENT

Total meal replacement with a limit of 800 kilocalories per day

Interventions

Semaglutide Pen Injector [Ozempic]

Glucagon-like peptide 1 (GLP-1) receptor agonist

Intervention Type: DRUG

Very-low Calorie Diet

Total meal replacement with a limit of 800 kilocalories per day

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Confirmed Type 2 Diabetes Mellitus
• Body mass index > 27kg·m-2
• Eligible for VLCD, Semaglutide (or both), within routine practice
• Ability to provide informed consent

Exclusion Criteria

• BMI > 50kg·m-2
• Current pregnancy or breastfeeding, or intention to fall pregnant within the next 3 months
• Uncontrolled hypertension (blood pressure >200/120mmHg)
• Current treatment with insulin
• Current or recent use of GLP-1 agonists
• Previous adverse reaction to a GLP-1 agonist
• Current or recent involvement in a VLCD programme (within the last 12 months)
• History of >5% weight loss within the preceding 12 months
• Ingestion of exogenous D2O within the preceding 12 months
• Background of clinically significant cardiovascular, cerebrovascular or respiratory disease, neurological disorders or musculoskeletal problems
• History of malignancy undergoing current treatment or palliation
• History of any medical condition contraindicating the use of GLP-1 agonist medication
• Any other medical condition deemed by the investigators to preclude inclusion into the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Iskandar Idris

Role: PRINCIPAL_INVESTIGATOR

Professor in Diabetes and Vascular Medicine & Honorary Consultant

Locations

University of Nottingham, Royal Derby Hospital Centre

Derby, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Facility Contacts

Philip Atherton, BSc MSc PhD

Role: primary

philip.atherton@nottingham.ac.uk

01332724622

Other Identifiers

21031

Identifier Type: -

Identifier Source: org_study_id