Type 2 Diabetes Mellitus in ObesePhase 4SemVLCDNCT05606471
Glucagon-like Peptide-1 Agonism With Very Low Calorie Diets
A Phase 4 study testing Semaglutide Pen Injector [Ozempic] and Very-low Calorie Diet in people with Type 2 Diabetes Mellitus in Obese, run by University of Nottingham at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus in Obese
- What is being tested?
- Semaglutide Pen Injector [Ozempic] and Very-low Calorie Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Sep 2021to 28 Jul 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University of Nottingham, Royal Derby Hospital Centre
Derby, DE22 3DT
Philip Atherton, BSc MSc PhD, 01332724622, philip.atherton@nottingham.ac.uk
Iskandar Idris
About this study
Official title: The Anabolic Effects of GLP-1 Agonism to Prevent Lean Muscle Losses During Very-low Calorie Diets (VLCDs) for Weight Loss
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.
Read more
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:
- Semaglutide only
- VLCD only
- 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
- Being tested
- Semaglutide Pen Injector [Ozempic], Very-low Calorie Diet
- Keywords
- Type 2 diabetes, Obesity, GLP-1, Semaglutide, VLCD
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide Pen Injector [Ozempic]Drug
Glucagon-like peptide 1 (GLP-1) receptor agonist
Very-low Calorie DietDietary supplement
Total meal replacement with a limit of 800 kilocalories per day
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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). Receives: Drug: Semaglutide Pen Injector [Ozempic]; Dietary Supplement: Very-low Calorie Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle protein synthesis rate
Measuring the rate of skeletal muscle growth in vivo by determining the rate of deuterium incorporation into muscle
Measured: 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
Measured: 6 weeks
Secondary outcomes (11)
Skeletal muscle mass
Determined from DXA scanning (measured in kg and percentage of total body weight) and novel techniques using rate of appearance of a creatine tracer in urine after an initial bolus
Measured: 12 weeks
Fat mass
Determined from DXA scanning (measured in kg and percentage of total body weight)
Measured: 12 weeks
Total body weight
Measured in kg
Measured: 12 weeks
Whole body insulin sensitivity
Determined using the intravenous glucose tolerance test and measures of fasting insulin \& glucose
Measured: 12 weeks
Pancreatic beta cell function
Determined using the intravenous glucose tolerance test and measures of fasting insulin \& glucose
Measured: 12 weeks
Skeletal muscle strength
Determined from maximal voluntary contraction (MVC) of left knee extension
Measured: 12 weeks
Skeletal neuromuscular function
Assessed using measurement of force stability during electromyography
Measured: 12 weeks
Gross skeletal muscle function
Measured using a short battery of physical performance tests (SBPPT) to give an overall score of skeletal gross skeletal muscle function (scored out of 12)
Measured: 12 weeks
Right vastus lateralis muscle thickness
Determined from muscle ultrasonography
Measured: 12 weeks
Right vastus lateralis muscle cross sectional area (CSA)
Determined from muscle ultrasonography
Measured: 12 weeks
Right vastus lateralis muscle fibre pennation angle
Determined from muscle ultrasonography
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2022
- Study start15 Sep 2021
- Primary completion28 Jul 2023 (estimated)
- Study completion28 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes Mellitus in ObeseStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Responsible party
- Sponsor
- Investigators
- Iskandar Idris, Principal investigator, Professor in Diabetes and Vascular Medicine & Honorary Consultant
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05606471
- Sponsor's protocol ID
- 21031
- Acronym
- SemVLCD
- Status last verified
- Oct 2022
- First submitted
- 23 May 2022
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Langer HT, Gilmore NK, Hayden CMT, Roux J, Bariohay B, Rouquet T, Awada M, Marcotorchino J, Bournot L, Nunn E, Titchenell PM, Liskiewicz D, Muller TD, Anyiam O, Atherton PJ, Idris I, Hentschel A, Roos A, Haritonow N, Norman K, Muller-Werdan U, Baar K. Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans. Cell Rep Med. 2026 Mar 17;7(3):102665. doi: 10.1016/j.xcrm.2026.102665.
PubMed 41850248
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Anabolic Effects of GLP-1 Agonism to Prevent Lean Muscle Losses During Very-low Calorie Diets (VLCDs) for Weight Loss
- ClinicalTrials.gov ID
- NCT05606471
- Acronym / sponsor ID
- SemVLCD / 21031
- Conditions
- Type 2 Diabetes Mellitus in Obese
- Keywords
- Type 2 diabetes, Obesity, GLP-1, Semaglutide, VLCD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 28 Jul 2023 (estimated)
- Study completion
- 28 Jul 2023 (estimated)
- First posted
- 4 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Semaglutide only
- VLCD only
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VLCD only | Active comparator | Dietary Supplement: Very-low Calorie DietParticipants 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. |
| Semaglutide only | Active comparator | Drug: Semaglutide Pen Injector [Ozempic]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. |
| Combined VLCD plus Semaglutide | Experimental | Drug: Semaglutide Pen Injector [Ozempic], Dietary Supplement: Very-low Calorie DietParticipants in this group will both partake in the VLCD, and take the weekly dose of Semaglutide (as described above). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide Pen Injector [Ozempic]Glucagon-like peptide 1 (GLP-1) receptor agonist | Drug | Combined VLCD plus Semaglutide, Semaglutide only |
| Very-low Calorie DietTotal meal replacement with a limit of 800 kilocalories per day | Dietary supplement | Combined VLCD plus Semaglutide, VLCD only |
Primary outcome
Muscle protein synthesis rate
Time frame: 6 weeks
Measuring the rate of skeletal muscle growth in vivo by determining the rate of deuterium incorporation into muscle
Muscle protein breakdown rate
Time frame: 6 weeks
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
11 secondary outcomes
Skeletal muscle mass
Time frame: 12 weeks
Fat mass
Time frame: 12 weeks
Total body weight
Time frame: 12 weeks
Whole body insulin sensitivity
Time frame: 12 weeks
Pancreatic beta cell function
Time frame: 12 weeks
Skeletal muscle strength
Time frame: 12 weeks
Skeletal neuromuscular function
Time frame: 12 weeks
Gross skeletal muscle function
Time frame: 12 weeks
Right vastus lateralis muscle thickness
Time frame: 12 weeks
Right vastus lateralis muscle cross sectional area (CSA)
Time frame: 12 weeks
Right vastus lateralis muscle fibre pennation angle
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Derived from this study: PubMed 41850248Langer HT, Gilmore NK, Hayden CMT, Roux J, Bariohay B, Rouquet T, Awada M, Marcotorchino J, Bournot L, Nunn E, Titchenell PM, Liskiewicz D, Muller TD, Anyiam O, Atherton PJ, Idris I, Hentschel A, Roos A, Haritonow N, Norman K, Muller-Werdan U, Baar K. Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans. Cell Rep Med. 2026 Mar 17;7(3):102665. doi: 10.1016/j.xcrm.2026.102665.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
University of Nottingham, Royal Derby Hospital Centre
Derby, United Kingdom
Iskandar Idris principal investigator
Professor in Diabetes and Vascular Medicine & Honorary Consultant
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Semaglutide Pen Injector [Ozempic] and Very-low Calorie Diet in people with Type 2 Diabetes Mellitus in Obese, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle protein synthesis rate (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05606471, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.