Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus.

Anyiam O, Phillips B, Quinn K, Wilkinson D, Smith K, Atherton P, Idris I

Clinical nutrition (Edinburgh, Scotland)2 Jul 2024Cited by 35 (Europe PMC)

PMID38996661DOI10.1016/j.clnu.2024.06.034PepBankPUB-38996661

Publisher page PubMedAsk about this study

Summary

Background & aimsVery-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes.MethodsThirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR.ResultsSignificantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01).ConclusionVLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study15

8 results from studies that gave the peptide. 8 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, HbA1c fell significantly from baseline in the semaglutide-alone group over 12 weeks.
In plain wordsIn adults with type 2 diabetes, HbA1c fell over 12 weeks in the group that took semaglutide alone.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666101
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, fasting glucose fell significantly from baseline in the semaglutide-alone group over 12 weeks.
In plain wordsIn adults with type 2 diabetes, fasting glucose fell over 12 weeks in the group that took semaglutide alone.
Peptide
Semaglutide
Outcome
DecreaseFasting glucose change
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666102
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, fasting insulin did not improve in the semaglutide-alone group over 12 weeks; it improved only in the VLCD and combination groups.
In plain wordsIn adults with type 2 diabetes, fasting insulin did not improve with semaglutide alone over 12 weeks.
Peptide
Semaglutide
Outcome
No significant changeFasting insulin change
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666103
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, HOMA-IR did not improve in the semaglutide-alone group over 12 weeks; it improved only in the VLCD and combination groups.
In plain wordsIn adults with type 2 diabetes, estimated insulin resistance did not improve with semaglutide alone over 12 weeks.
Peptide
Semaglutide
Outcome
No significant changeHOMA-IR change
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666104
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, the insulin first phase response during IVGTT increased in the semaglutide-alone group over 12 weeks.
In plain wordsIn adults with type 2 diabetes, a measure of beta-cell insulin response rose over 12 weeks in the group that took semaglutide alone.
Peptide
Semaglutide
Outcome
IncreaseInsulin first phase response during IVGTT
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Source sentences
Summary
Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01).
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666105
06HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, weight loss with semaglutide alone over 12 weeks was 5.4 percentage points smaller than with a very-low calorie diet.
In plain wordsIn adults with type 2 diabetes, semaglutide alone gave less weight loss over 12 weeks than a very-low calorie diet.
Peptide
Semaglutide
Outcome
DecreaseWeight loss versus VLCD
Study
n: not reported in source
Comparator
800 kcal/day VLCD
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Measurements
Weight loss difference (VLCD minus semaglutide)
5.4 percentage points
VLCD vs semaglutide
Source sentences
Summary
VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both).
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666106
07HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, fat mass fell less with semaglutide alone than with a very-low calorie diet over 12 weeks.
In plain wordsIn adults with type 2 diabetes, semaglutide alone reduced body fat less than a very-low calorie diet did.
Peptide
Semaglutide
Outcome
DecreaseFat mass reduction versus VLCD and combination
Study
n: not reported in source
Comparator
800 kcal/day VLCD
Outcome group
Body composition · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Source sentences
Summary
Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both).
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666107
08HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, adding semaglutide to a very-low calorie diet gave a significantly greater increase in the insulin first phase response than the diet alone.
In plain wordsIn adults with type 2 diabetes, adding semaglutide to a very-low calorie diet improved a beta-cell insulin response more than the diet alone.
Peptide
Semaglutide
Outcome
IncreaseInsulin first phase response: combination versus VLCD alone
Study
n: not reported in source
Comparator
800 kcal/day VLCD alone
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Source sentences
Summary
Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01).
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
Show in the study text Report a problemFND-3899666108

Studies that did not test the peptide alone7

In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semaglutide.

09HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, semaglutide plus a very-low calorie diet gave 7 percentage points greater weight loss than semaglutide alone over 12 weeks.
In plain wordsIn adults with type 2 diabetes, semaglutide plus a very-low calorie diet gave more weight loss than semaglutide alone.
Peptide
Semaglutide
Outcome
DecreaseWeight loss: combination versus semaglutide alone
Study
n: not reported in source
Comparator
Semaglutide alone
Outcome group
Body weight · Metabolic and weight
Measurements
Weight loss difference (combination minus semaglutide)
7 percentage points
combination vs semaglutide
Source sentences
Summary
VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both).
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3899666109
10HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, HbA1c fell significantly from baseline with semaglutide plus a very-low calorie diet over 12 weeks.
In plain wordsIn adults with type 2 diabetes, HbA1c fell over 12 weeks with semaglutide plus a very-low calorie diet.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change with the combination
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3899666110
11HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, fasting glucose fell significantly from baseline with semaglutide plus a very-low calorie diet over 12 weeks.
In plain wordsIn adults with type 2 diabetes, fasting glucose fell over 12 weeks with semaglutide plus a very-low calorie diet.
Peptide
Semaglutide
Outcome
DecreaseFasting glucose change with the combination
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3899666111
12HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, fasting insulin improved with semaglutide plus a very-low calorie diet over 12 weeks.
In plain wordsIn adults with type 2 diabetes, fasting insulin improved with semaglutide plus a very-low calorie diet.
Peptide
Semaglutide
Outcome
Direction not reportedFasting insulin change with the combination
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3899666112
13HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, HOMA-IR improved with semaglutide plus a very-low calorie diet over 12 weeks.
In plain wordsIn adults with type 2 diabetes, estimated insulin resistance improved with semaglutide plus a very-low calorie diet.
Peptide
Semaglutide
Outcome
Direction not reportedHOMA-IR change with the combination
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only.
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3899666113
14HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, the insulin first phase response during IVGTT increased with semaglutide plus a very-low calorie diet over 12 weeks.
In plain wordsIn adults with type 2 diabetes, a beta-cell insulin response rose with semaglutide plus a very-low calorie diet.
Peptide
Semaglutide
Outcome
IncreaseInsulin first phase response with the combination
Study
n: not reported in source
Comparator
Baseline
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01).
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3899666114
15HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, semaglutide plus a very-low calorie diet reduced fat mass more than semaglutide alone over 12 weeks.
In plain wordsIn adults with type 2 diabetes, semaglutide plus a very-low calorie diet reduced body fat more than semaglutide alone.
Peptide
Semaglutide
Outcome
DecreaseFat mass reduction: combination versus semaglutide alone
Study
n: not reported in source
Comparator
Semaglutide alone
Outcome group
Body composition · Metabolic and weight
Source sentences
Summary
Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both).
1 context sentence(design, population, supporting numbers)
Summary · context
Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m^-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3899666115

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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