Evidence map›Paper›PMID 41715239›Full record

ReviewCardiovascular diabetology. Endocrinology reports2026

Efficacy and safety of orforglipron, an oral small-molecule GLP-1 receptor agonist, on cardiometabolic outcomes: a meta-analysis and systematic review.

Adir Alper, Gal Peleg, Adina Fagin, Priyansh Shah, Ishmum Chowdhury, Antony Gonzales, Robert Faillace

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Cardiovascular diabetology. Endocrinology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Adir AlperJacobi Medical Center, AECOM, 4857 Broadway, New York, NY, 10034, USA. alpera@nychhc.org.
Gal PelegMedStar Washington Hospital Center, Washington, DC, USA.
Adina FaginJacobi Medical Center, AECOM, 4857 Broadway, New York, NY, 10034, USA.
Priyansh ShahJacobi Medical Center, AECOM, 4857 Broadway, New York, NY, 10034, USA.
Ishmum ChowdhuryJacobi Medical Center, AECOM, 4857 Broadway, New York, NY, 10034, USA.
Antony GonzalesJacobi Medical Center, AECOM, 4857 Broadway, New York, NY, 10034, USA.
Robert FaillaceJacobi Medical Center, AECOM, 4857 Broadway, New York, NY, 10034, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundObesity and type 2 diabetes are the primary drivers of atherosclerotic cardiovascular disease (ASCVD), the leading cause of death worldwide. Injectable GLP-1 receptor agonists reduce major adverse cardiovascular events. Yet for many individuals, injection hesitancy remains a significant barrier to long-term adherence. Orforglipron is a novel once-daily oral non-peptide GLP-1 receptor agonist designed to provide comprehensive cardiometabolic risk reduction.

methodsPRISMA-compliant systematic review and meta-analysis (PROSPERO CRD420251229397) of placebo-controlled phase 2 and phase 3 trials of orforglipron. Random-effects models were used to pool mean differences (MD) and risk ratios (RR) with 95% confidence intervals.

resultsAcross four large trials, orforglipron produced dose-dependent, clinically meaningful improvements in major modifiable cardiovascular risk factor compared with placebo: body weight − 6.08% (95% CI − 7.68 to − 4.47; up to − 9.31% at higher doses), HbA1c − 0.85% (95% CI − 1.53 to − 0.18; up to − 1.36%), systolic blood pressure − 4.32 mmHg (95% CI − 5.61 to − 3.03; up to − 5.78 mmHg at 45 mg), LDL-cholesterol − 4.14% (95% CI − 6.38 to − 1.91), triglycerides − 10.90% (95% CI − 14.36 to − 7.43), VLDL-cholesterol − 10.81% (95% CI − 14.10 to − 7.51), and HDL-cholesterol + 3.31% (95% CI + 1.66 to + 4.97). Notably, heterogeneity was very low to absent (I² = 0%) for systolic blood pressure and all lipid outcomes. Gastrointestinal side effects were common but typical of the GLP-1 class (nausea RR 5.22, vomiting RR 3.24, eructation RR 6.80).

conclusionOrforglipron provides highly consistent reductions across the full spectrum of ASCVD risk factors, with effect sizes on lipids and blood pressure comparable to those linked to MACE reduction in trials of injectable GLP-1 receptor agonists. As a novel small-molecule GLP-1 agonist in its class, Orforglipron offers a transformative option for comprehensive cardiometabolic risk reduction and ASCVD prevention in patients with obesity and type 2 diabetes.

Indexed as

Cardiometabolic riskOral GLP-1 receptor agonistOrforglipronType 2 diabetes mellitus

Identifiers

PMID41715239
PMCPMC12922244

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.