Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

Lu Y, Chen J, Guo Y, Ding H, Liu YL, Van Name MA, Sharifi M, Lu Y, Chen Y

Diabetes, obesity & metabolism16 Apr 2026Cited by 3 (Europe PMC)

PMID41992023PMCIDPMC13243969DOI10.1111/dom.70742PepBankPUB-41992023

Summary

AimsTo characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).Materials and methodsPubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity. The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure. Secondary outcomes included treatment effects for each individual CEI component.ResultsNineteen RCTs (N = 13 117) were analysed. Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%. CEI rankings were generally consistent across T2D and non-T2D subgroups. Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63).ConclusionsHigher-dose GLP-1 receptor mono-agonists, particularly semaglutide 7.2 mg and orforglipron 36 mg (Foundayo 17.2 mg tablet), demonstrated the most consistent multidimensional cardiometabolic improvements, although domain-specific differences were observed across agents.

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

Results from this study11

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

01HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, semaglutide 7.2 mg achieved the highest cardiometabolic efficacy index, 0.86.
In plain wordsIn adults with overweight or obesity, semaglutide 7.2 mg had the highest cardiometabolic efficacy index.
Peptide
Semaglutide
Outcome
Not applicableCardiometabolic efficacy index
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Studied dose
7.2 mgAs given in this study (human).
Measurements
cardiometabolic efficacy index
0.86
semaglutide 7.2 mg
Source sentences
Summary
Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%.
4 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Summary · context
The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure.
Summary · context
Nineteen RCTs (N = 13 117) were analysed.
Show in the study text Report a problemFND-4199202301
02HumanSystematic reviewEfficacy outcome
In non-T2D adults with overweight or obesity, oral semaglutide 25 mg had a CEI comparable to orforglipron 36 mg (0.63 versus 0.67).
In plain wordsIn adults with overweight or obesity without type 2 diabetes, oral semaglutide had a cardiometabolic index comparable to orforglipron.
Peptide
Semaglutide
Outcome
Not applicableCardiometabolic efficacy index
Study
n: not reported in source
Comparator
Orforglipron 36 mg
Analysis
Primary
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Studied dose
25 mg · oralAs given in this study (human).
Measurements
Cardiometabolic efficacy index
0.63
oral semaglutide 25 mg; non-T2D subgroup
Cardiometabolic efficacy index
0.67
orforglipron 36 mg; non-T2D subgroup
Source sentences
Summary
Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63).
4 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Summary · context
The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure.
Summary · context
Nineteen RCTs (N = 13 117) were analysed.
Show in the study text Report a problemFND-4199202303
03HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, semaglutide 2.4 mg achieved a cardiometabolic efficacy index of 0.66.
In plain wordsIn adults with overweight or obesity, semaglutide 2.4 mg had a cardiometabolic efficacy index of 0.66.
Peptide
Semaglutide
Outcome
Not applicableCardiometabolic efficacy index
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Studied dose
2.4 mgAs given in this study (human).
Measurements
cardiometabolic efficacy index
0.66
semaglutide 2.4 mg
Source sentences
Summary
Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%.
4 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Summary · context
The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure.
Summary · context
Nineteen RCTs (N = 13 117) were analysed.
Show in the study text Report a problemFND-4199202304
04HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, orforglipron 36 mg achieved a cardiometabolic efficacy index of 0.68.
In plain wordsIn adults with overweight or obesity, orforglipron 36 mg achieved a cardiometabolic efficacy index of 0.68.
Peptide
Orforglipron
Outcome
Not applicableCardiometabolic efficacy index
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Studied dose
36 mg · oralAs given in this study (human).
Measurements
Cardiometabolic efficacy index (CEI)
0.68 index (0 to 1)
orforglipron 36 mg, network meta-analysis
Source sentences
Summary
Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%.
2 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Show in the study text Report a problemFND-4199202308
05HumanSystematic reviewEfficacy outcome
In adults without diabetes, orforglipron 36 mg had a CEI comparable to oral semaglutide 25 mg, at 0.67 versus 0.63.
In plain wordsIn adults without diabetes, orforglipron 36 mg had a cardiometabolic index comparable to oral semaglutide 25 mg.
Peptide
Orforglipron
Outcome
No significant changeCEI in non-T2D adults
Study
n: not reported in source
Comparator
Oral semaglutide 25 mg
Analysis
Primary
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Studied dose
36 mg · oralAs given in this study (human).
Measurements
Cardiometabolic efficacy index (CEI)
0.67 index (0 to 1)
orforglipron 36 mg, non-T2D adults
Cardiometabolic efficacy index (CEI)
0.63 index (0 to 1)
oral semaglutide 25 mg comparator, non-T2D adults
Source sentences
Summary
Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63).
2 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Show in the study text Report a problemFND-4199202311
06HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, semaglutide 7.2 mg had placebo-adjusted weight reduction of at least 10%.
In plain wordsIn adults with overweight or obesity, semaglutide 7.2 mg reduced weight by at least 10% more than placebo.
Peptide
Semaglutide
Outcome
DecreasePlacebo-adjusted weight reduction
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
7.2 mgAs given in this study (human).
Measurements
placebo-adjusted weight reduction
≥ 10%
semaglutide 7.2 mg
Source sentences
Summary
Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%.
4 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Summary · context
Secondary outcomes included treatment effects for each individual CEI component.
Summary · context
Nineteen RCTs (N = 13 117) were analysed.
Show in the study text Report a problemFND-4199202302
07HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, semaglutide 2.4 mg had placebo-adjusted weight reduction of at least 10%.
In plain wordsIn adults with overweight or obesity, semaglutide 2.4 mg reduced weight by at least 10% more than placebo.
Peptide
Semaglutide
Outcome
DecreasePlacebo-adjusted weight reduction
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mgAs given in this study (human).
Measurements
Placebo-adjusted weight reduction
≥ 10%
semaglutide 2.4 mg; lower bound rather than a 10% point estimate
Source sentences
Summary
Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%.
4 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Summary · context
Secondary outcomes included treatment effects for each individual CEI component.
Summary · context
Nineteen RCTs (N = 13 117) were analysed.
Show in the study text Report a problemFND-4199202305
08HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity, orforglipron 36 mg achieved placebo-adjusted weight reduction ≥ 10%.
In plain wordsIn adults with overweight or obesity, orforglipron 36 mg reduced weight more than placebo.
Peptide
Orforglipron
Outcome
DecreasePlacebo-adjusted weight reduction
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
36 mg · oralAs given in this study (human).
Measurements
Placebo-adjusted weight reduction
≥ 10%
orforglipron 36 mg, network meta-analysis
Source sentences
Summary
Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%.
2 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Show in the study text Report a problemFND-4199202309

Studies that did not test the peptide alone3

In this study, the peptide 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 the peptide.

09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, pooled GLP-1 receptor mono-agonist CEI rankings were generally consistent across T2D and non-T2D subgroups.
In plain wordsIn adults with overweight or obesity, pooled GLP-1 drug rankings were generally consistent between people with and without type 2 diabetes.
Peptide
Semaglutide
Outcome
Not applicableConsistency of cardiometabolic efficacy index rankings across diabetes subgroups
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Source sentences
Summary
CEI rankings were generally consistent across T2D and non-T2D subgroups.
4 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Summary · context
The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure.
Summary · context
Nineteen RCTs (N = 13 117) were analysed.
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-4199202306
10HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, pooled GLP-1 receptor mono-agonist CEI rankings were generally consistent across T2D and non-T2D subgroups.
In plain wordsIn adults with overweight or obesity, pooled GLP-1 drug rankings were generally consistent between people with and without type 2 diabetes.
Peptide
Liraglutide
Outcome
Not applicableConsistency of cardiometabolic efficacy index rankings across diabetes subgroups
Study
n: not reported in source
Analysis
Primary
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Source sentences
Summary
CEI rankings were generally consistent across T2D and non-T2D subgroups.
4 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
Summary · context
The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure.
Summary · context
Nineteen RCTs (N = 13 117) were analysed.
In this study, Liraglutide 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 Liraglutide.
Show in the study text Report a problemFND-4199202307
11HumanNot a test of Orforglipron aloneSystematic reviewEfficacy outcome
In adults with overweight or obesity, GLP-1 mono-agonist CEI rankings were generally consistent across diabetes subgroups.
In plain wordsIn adults with overweight or obesity, pooled drug rankings were generally consistent across diabetes subgroups.
Peptide
Orforglipron
Outcome
No significant changeCEI subgroup rankings
Study
n: not reported in source
Comparator
T2D versus non-T2D subgroups
Outcome group
Cardiometabolic risk factors · Metabolic and weight
Source sentences
Summary
CEI rankings were generally consistent across T2D and non-T2D subgroups.
2 context sentences(design, population, supporting numbers)
Summary · context
To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).
Summary · context
PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity.
In this study, Orforglipron 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 Orforglipron.
Show in the study text Report a problemFND-4199202310

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.

Versions 5 to 16Current
28 Oct 2026, 02:03 UTC
The same notice was added 12 times, first on 14 Oct 2026, 05:02 UTC. The status did not change between them.
Study results updated
Version 4
14 Oct 2026, 01:46 UTC
Study data updated · source update from Europe PMC
Version 3
12 Oct 2026, 11:11 UTC
Study results updated
Version 2
9 Oct 2026, 03:06 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

Summary

Results from this study11

Studies that did not test the peptide alone3

Version history

Subjects

Publication types

MeSH terms

Keywords