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

NCT05606471 | Unknown Phase 4

• 1 other identifier: 21031
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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. 1.Semaglutide only
2. 2.VLCD only
3. 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.

Conditions

Type 2 Diabetes Mellitus in Obese

Keywords

Type 2 diabetes; Obesity; GLP-1; Semaglutide; VLCD

Outcome Measures

Primary Outcomes (2)

• Muscle protein synthesis rate

  Measuring the rate of skeletal muscle growth in vivo by determining the rate of deuterium incorporation into muscle

  6 weeks

• Muscle protein breakdown rate

  Measuring the rate of breakdown of skeletal muscle in vivo using the rate of appearance of deuterium-labelled 3-methyl-histidine in blood after an initial oral bolus

  6 weeks

Secondary Outcomes (11)

• Skeletal muscle mass

  12 weeks

• Fat mass

  12 weeks

• Total body weight

  12 weeks

• Whole body insulin sensitivity

  12 weeks

• Pancreatic beta cell function

  12 weeks

Study Arms (3)

VLCD only

ACTIVE COMPARATOR

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.

Dietary Supplement: Very-low Calorie Diet

Semaglutide only

ACTIVE COMPARATOR

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.

Drug: Semaglutide Pen Injector [Ozempic]

Combined VLCD plus Semaglutide

EXPERIMENTAL

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

Drug: Semaglutide Pen Injector [Ozempic]; Dietary Supplement: Very-low Calorie Diet

Interventions

Semaglutide Pen Injector [Ozempic] DRUG

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

Combined VLCD plus Semaglutide; Semaglutide only

Very-low Calorie Diet DIETARY_SUPPLEMENT

Total meal replacement with a limit of 800 kilocalories per day

Combined VLCD plus Semaglutide; VLCD only

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nottingham: lead
• Medical Research Council: collaborator

Study Sites (1)

University of Nottingham, Royal Derby Hospital Centre

Derby, DE22 3DT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Iskandar Idris

  Professor in Diabetes and Vascular Medicine & Honorary Consultant

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: November 4, 2022
• Study Start: September 15, 2021
• Primary Completion: July 28, 2023
• Study Completion: July 28, 2023
• Last Updated: November 4, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)