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Study · Randomized controlled trial · 2025

8 results

Treatment with orforglipron, an oral glucagon like peptide-1 receptor agonist, is associated with improvements of CV risk biomarkers in participants with type 2 diabetes or obesity without diabetes.

Wharton S, Rosenstock J, Konige M, Lin Y, Duffin K, Wilson J, Banerjee H, Pirro V, Kazda C, Mather K

Cardiovascular diabetology6 Jun 2025Cited by 16 (Europe PMC)

PMID40481478 (opens in a new tab)PMCIDPMC12142847 (opens in a new tab)DOI10.1186/s12933-025-02781-x (opens in a new tab)PepBankPUB-40481478
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Summary

BackgroundOrforglipron, a novel oral, non-peptide glucagon like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving body weight reduction and glycemic control. However, its potential benefits in improving cardiovascular (CV) risk factors have yet to be determined. We assessed the effect of orforglipron in participants with type 2 diabetes (T2D) and/or overweight or obesity on blood pressure, lipid, and inflammatory biomarkers associated with risk for major adverse cardiovascular events.MethodsUsing data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers. For the T2D study, participants mean age 59 years, 40% were assigned female at birth with a mean HbA1c of 8.1% and mean BMI of 35.3 kg/m2; they received once daily orforglipron doses (3, 12, 24, 36, or 45 mg) or once weekly subcutaneous dulaglutide 1.5 mg, or placebo. In the obesity study, participants had a mean age 54 years, 60% were assigned female at birth, and mean BMI was 37.9 kg/m2; they received once daily orforglipron (12, 24, 36, or 45 mg) or placebo. The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure, lipids (cholesterol, triglycerides, Apolipoprotein B (ApoB), Apolipoprotein C3 (ApoC3), N-terminal pro-b-type natriuretic peptide (NT-pro-BNP), and inflammatory biomarkers (high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6)) were assessed.ResultsSignificant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity. In both studies, improvements in blood pressure, lipid parameters, and most of the evaluated biomarkers were of similar magnitude after treatment with 12 mg orforglipron as with 24, 36, and 45 mg.ConclusionOrforglipron treatment was associated with beneficial changes in CV risk markers in participants with T2D and in participants with overweight/obesity without T2D. (Clinicaltrials.gov: NCT05048719, NCT05051579).
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

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

  1. 01HumanRandomized controlled trialEfficacy outcome

    In participants with diabetes or overweight or obesity, orforglipron decreased blood pressure versus placebo.

    In plain wordsOrforglipron decreased blood pressure versus placebo in participants with diabetes or overweight or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseBlood pressure
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Blood pressure · Cardiovascular
    Studied dose
    Dose not stated · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure
  2. 02HumanRandomized controlled trialEfficacy outcome

    In participants with diabetes or overweight or obesity, orforglipron decreased LDL cholesterol versus placebo.

    In plain wordsOrforglipron decreased LDL cholesterol versus placebo in participants with diabetes or overweight or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseLDL cholesterol
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    Dose not stated · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure
  3. 03HumanRandomized controlled trialEfficacy outcome

    In participants with diabetes or overweight or obesity, orforglipron decreased triglycerides versus placebo.

    In plain wordsOrforglipron decreased triglycerides versus placebo in participants with diabetes or overweight or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseTriglycerides
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    Dose not stated · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure
  4. 04HumanRandomized controlled trialEfficacy outcome

    In participants with diabetes or overweight or obesity, orforglipron decreased ApoB versus placebo.

    In plain wordsOrforglipron decreased ApoB versus placebo in participants with diabetes or overweight or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseApoB
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    Dose not stated · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure
  5. 05HumanRandomized controlled trialEfficacy outcome

    In participants with diabetes or overweight or obesity, orforglipron decreased ApoC3 versus placebo.

    In plain wordsOrforglipron decreased ApoC3 versus placebo in participants with diabetes or overweight or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreaseApoC3
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    Dose not stated · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure
  6. 06HumanRandomized controlled trialEfficacy outcome

    In participants with diabetes or overweight or obesity, orforglipron decreased hsCRP versus placebo.

    In plain wordsOrforglipron decreased the inflammation marker hsCRP versus placebo in participants with diabetes or overweight or obesity.

    Peptide
    Orforglipron
    Outcome
    DecreasehsCRP
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    Significant placebo-adjusted decreases from baseline in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, ApoB, ApoC3, and hsCRP were observed following orforglipron treatment in participants with T2D and/or overweight or obesity.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure
  7. 07HumanRandomized controlled trialEfficacy outcome

    In both studies, blood pressure improved similarly with 12 mg orforglipron and with 24, 36, and 45 mg.

    In plain wordsIn both studies, blood pressure improved similarly with 12 mg orforglipron and with 24, 36, and 45 mg.

    Peptide
    Orforglipron
    Outcome
    No significant changeBlood pressure dose comparison
    Study

    n: not reported in source

    Comparator
    24, 36, and 45 mg orforglipron
    Analysis
    Exploratory
    Outcome group
    Blood pressure · Cardiovascular
    Studied dose
    12 mg · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    In both studies, improvements in blood pressure, lipid parameters, and most of the evaluated biomarkers were of similar magnitude after treatment with 12 mg orforglipron as with 24, 36, and 45 mg.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure
  8. 08HumanRandomized controlled trialEfficacy outcome

    In both studies, lipid parameters improved similarly with 12 mg orforglipron and with 24, 36, and 45 mg.

    In plain wordsIn both studies, lipid parameters improved similarly with 12 mg orforglipron and with 24, 36, and 45 mg.

    Peptide
    Orforglipron
    Outcome
    No significant changeLipid parameter dose comparison
    Study

    n: not reported in source

    Comparator
    24, 36, and 45 mg orforglipron
    Analysis
    Exploratory
    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    12 mg · oral · 26 weeks (T2D study) or 36 weeks (obesity study)As given in this study (human).

    Source sentences

    Summary
    In both studies, improvements in blood pressure, lipid parameters, and most of the evaluated biomarkers were of similar magnitude after treatment with 12 mg orforglipron as with 24, 36, and 45 mg.
    2 context sentences
    Summary · context
    Using data from participants with available samples from Phase 2 trials of orforglipron in participants with T2D (N = 361) or with overweight or obesity without diabetes mellitus (N = 234), we performed an exploratory analysis of changes in CV risk markers.
    Summary · context
    The change from baseline at 26 weeks (T2D study) or 36 weeks (obesity study) in blood pressure

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

Registered trials2

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

2 trials · 2 completed · 2 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2Results postedNCT05051579

A Study of LY3502970 in Participants With Obesity or Overweight With Weight-related Comorbidities

Eli Lilly and Companyn = 27229 Sept 2021 to 22 Nov 2022

Obesity · Overweight and Obesity

Trial pageClinicalTrials.govUpdated 13 Sept 2023
CompletedPhase 2Results postedNCT05048719

A Study of LY3502970 in Participants With Type 2 Diabetes Mellitus

Eli Lilly and Companyn = 38315 Sept 2021 to 30 Sept 2022

Type 2 Diabetes

Trial pageClinicalTrials.govUpdated 17 Oct 2023

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 3Current

    21 Oct 2026, 18:59 UTC

    Study data updated · source update from Europe PMC

  2. Version 2

    14 Oct 2026, 05:02 UTC

    Study results updated

  3. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

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Terms as the source lists them.

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