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Study · Systematic review · 2025

6 results

The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis.

Zhou J, Wang F, Li S

Frontiers in endocrinology10 Dec 2025Cited by 3 (Europe PMC)

PMID41450584 (opens in a new tab)PMCIDPMC12727569 (opens in a new tab)DOI10.3389/fendo.2025.1646956 (opens in a new tab)PepBankPUB-41450584
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Summary

ObjectiveThis study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.MethodsElectronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity. Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes.ResultsEight studies with low bias risk involving 1,454 participants were analysed. Meta-analysis results demonstrated that danuglipron significantly decreased HbA1c (mean difference [MD]: -0.90; 95% CI: -1.06, -0.74), FPG (MD: -24.66; 95% CI: -30.45, -18.86) and weight (MD: -2.17; 95% CI: -3.10, -1.23) and improved FPI (MD: 2.94; 95% CI: 1.50, 4.38). Orforglipron also showed significant positive effects on HbA1c (MD: -1.02; 95% CI: -1.18, -0.86), FPG (MD: -26.91; 95% CI: -31.05, -22.78), weight (MD: -6.28; 95% CI: -8.45, -4.11) and BMI (MD: -2.64; 95% CI: -3.38, -1.89). However, both danuglipron and orforglipron were associated with the occurrence of treatment-related adverse events and gastrointestinal adverse events (AEs).ConclusionThe oral GLP-1 RAs danuglipron and orforglipron are capable of improving blood glucose levels and reducing weight; however, they also pose an increased risk of gastrointestinal AEs. Further longitudinal studies are warranted to gain a deeper understanding of their efficacy, safety and tolerability.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In patients with diabetes or obesity, orforglipron significantly decreased HbA1c from baseline.

    In plain wordsOrforglipron significantly decreased HbA1c from baseline in patients with diabetes or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseHbA1c
    Study

    n: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Mean difference
    −1.02
    HbA1c
    95% CI of mean difference
    −1.18 to −0.86
    HbA1c

    Source sentences

    Summary
    Orforglipron also showed significant positive effects on HbA1c (MD: -1.02; 95% CI: -1.18, -0.86), FPG (MD: -26.91; 95% CI: -31.05, -22.78), weight (MD: -6.28; 95% CI: -8.45, -4.11) and BMI (MD: -2.64; 95% CI: -3.38, -1.89).
    3 context sentences
    Summary · context
    This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.
    Summary · context
    Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity.
    Summary · context
    Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes.
  2. 02HumanSystematic reviewEfficacy outcome

    In patients with diabetes or obesity, orforglipron significantly decreased fasting plasma glucose from baseline.

    In plain wordsOrforglipron significantly decreased fasting blood sugar from baseline in patients with diabetes or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseFasting plasma glucose
    Study

    n: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Mean difference
    −26.91
    FPG
    95% CI of mean difference
    −31.05 to −22.78
    FPG

    Source sentences

    Summary
    Orforglipron also showed significant positive effects on HbA1c (MD: -1.02; 95% CI: -1.18, -0.86), FPG (MD: -26.91; 95% CI: -31.05, -22.78), weight (MD: -6.28; 95% CI: -8.45, -4.11) and BMI (MD: -2.64; 95% CI: -3.38, -1.89).
    3 context sentences
    Summary · context
    This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.
    Summary · context
    Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity.
    Summary · context
    Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes.
  3. 03HumanSystematic reviewEfficacy outcome

    In patients with diabetes or obesity, orforglipron significantly decreased weight from baseline.

    In plain wordsOrforglipron significantly decreased weight from baseline in patients with diabetes or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseWeight
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Mean difference
    −6.28
    weight
    95% CI of mean difference
    −8.45 to −4.11
    weight, orforglipron, post-treatment versus baseline

    Source sentences

    Summary
    Orforglipron also showed significant positive effects on HbA1c (MD: -1.02; 95% CI: -1.18, -0.86), FPG (MD: -26.91; 95% CI: -31.05, -22.78), weight (MD: -6.28; 95% CI: -8.45, -4.11) and BMI (MD: -2.64; 95% CI: -3.38, -1.89).
    3 context sentences
    Summary · context
    This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.
    Summary · context
    Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity.
    Summary · context
    Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes.
  4. 04HumanSystematic reviewEfficacy outcome

    In patients with diabetes or obesity, orforglipron significantly decreased BMI from baseline.

    In plain wordsOrforglipron significantly decreased BMI from baseline in patients with diabetes or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseBMI
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Measurements

    Mean difference
    −2.64
    BMI
    95% CI of mean difference
    −3.38 to −1.89
    BMI, orforglipron, post-treatment versus baseline

    Source sentences

    Summary
    Orforglipron also showed significant positive effects on HbA1c (MD: -1.02; 95% CI: -1.18, -0.86), FPG (MD: -26.91; 95% CI: -31.05, -22.78), weight (MD: -6.28; 95% CI: -8.45, -4.11) and BMI (MD: -2.64; 95% CI: -3.38, -1.89).
    3 context sentences
    Summary · context
    This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.
    Summary · context
    Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity.
    Summary · context
    Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes.
  5. 05HumanSystematic reviewSafety outcome

    In patients with diabetes or obesity, orforglipron was associated with treatment-related adverse events.

    In plain wordsOrforglipron was linked to treatment-related adverse events in patients with diabetes or obesity.

    Peptide
    Orforglipron
    Outcome
    Not applicableTreatment-related adverse events
    Study

    n: not reported in source

    Outcome group
    Adverse events · Whole body
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Source sentences

    Summary
    However, both danuglipron and orforglipron were associated with the occurrence of treatment-related adverse events and gastrointestinal adverse events (AEs).
    3 context sentences
    Summary · context
    This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.
    Summary · context
    Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity.
    Summary · context
    Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes.
  6. 06HumanSystematic reviewSafety outcome

    In patients with diabetes or obesity, orforglipron was associated with gastrointestinal adverse events.

    In plain wordsOrforglipron was linked to digestive adverse events in patients with diabetes or obesity.

    Peptide
    Orforglipron
    Outcome
    Not applicableGastrointestinal adverse events
    Study

    n: not reported in source

    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    Dose not stated · oralAs given in this study (human).

    Source sentences

    Summary
    However, both danuglipron and orforglipron were associated with the occurrence of treatment-related adverse events and gastrointestinal adverse events (AEs).
    3 context sentences
    Summary · context
    This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.
    Summary · context
    Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron/orforglipron in patients with T2DM and/or obesity.
    Summary · context
    Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-/fixed-effects models, alongside safety outcomes.

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.

  1. Version 2Current

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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