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NotablePeer-reviewedVideo

An Oral GLP-1 Pill Delivers Injectable-Level Weight Loss

A once-daily small-molecule drug cut body weight by double digits in a large phase 3 obesity trial.

BySean Wharton, Louis J. Aronne, Adam Stefański, Nasreen Alfaris, Andreea Ciudin, Koutaro Yokote and 2 others

York University · McMaster University · Weill Cornell Medicine · Eli Lilly (United States) and 4 more

What it is

In a phase 3 trial of 3,127 adults with obesity but not diabetes, once-daily oral orforglipron produced a mean weight change of -11.2% at the top 36 mg dose over 72 weeks, compared with -2.1% for placebo. At that dose 54.6% of patients lost at least 10% of body weight and 18.4% lost at least 20%. Being a non-peptide small molecule, it can be made and taken as a simple pill rather than an injection.

Why it matters

Existing GLP-1 drugs are injectable peptides that are costly and supply-constrained. Orforglipron is the first oral small-molecule GLP-1 agonist to succeed in phase 3, reaching efficacy in the range of injectables while cutting mean body weight by -11.2% at the top dose versus -2.1% on placebo. A daily pill that is cheaper to manufacture could widen access to metabolic therapy dramatically.

Underlined numbers link to their source. Every metric and quoted figure is listed under Sources and data below.

Filed underobesity, GLP-1, metabolic, phase-3, drug

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A short explainer of this result.

Scored 2026-09-30How scoring works

The Frontier Score, in full

How this entry's score is built, term by term. Open any pillar to see each sub-metric's raw value, how it maps to 0 to 100, and the record that holds it.
Evidence 83Impact 88Novelty 46
The three pillars as one shape: a result strong on every axis fills the triangle.
How the Frontier Score is calculated for this breakthrough
TermScoreWeightPoints
EvidenceHow established and verifiable the result is.83× 0.2520.7
ImpactHow much the result matters, judged field-relative and by current momentum.88× 0.2521.9
NoveltyHow genuinely new the result is, and how fast-moving.46× 0.5023.0
Weighted pillars65.6
Frontier recency12 months since publication× 0.67
IntegrityNot retracted× 1
Frontier Score44
Confidence: Settled. Established evidence: about 127 citations across 5 independent indices. Corroborated beyond citations (1 clinical trial).Established evidence: about 127 citations across 5 independent indices. Corroborated beyond citations (1 clinical trial).

Every sub-metric, traced to its source

Evidence83
Evidence sub-metrics
Sub-metricRaw value0 to 100WeightPointsSource
Peer review & venueWhether the work has cleared peer review, and how selective its venue is. Peer review is necessary but not sufficient: before citations accrue, a fresh result in the most selective venues (Nature, Science, Cell, NEJM, the Lancet, PNAS, Physical Review Letters/X) is a stronger evidence signal than one in a legitimate but very high-volume mega-journal, which in turn outranks a preprint that has not been reviewed at all.Maps to 0 to 100: Peer-reviewed article graded by venue prestige: flagship 100, elite-family 90, high-volume mega-journal 78. Review 90, book 70, dataset 60, preprint 45, other 55.Peer-reviewed1000.3030.0OpenAlex type / primary_location / source
CorroborationIndependent corroboration that the result is real and being taken up, read as the BREADTH of agreement rather than the size of the citation pile. Counts how many of the five independent citation indices (OpenAlex, Crossref, Semantic Scholar, OpenCitations, Europe PMC) report the work at all, plus orthogonal, non-citation lines of corroboration: entry into the encyclopedia, registered clinical trials, released datasets or software, public funding on record, and technical-community discussion. Citation MAGNITUDE is deliberately judged under Impact, not here, so Evidence and Impact measure genuinely different things instead of both rewarding the same citation pile twice.Maps to 0 to 100: Starts at 28 and rises with each of the five independent citation indices that agree the work is cited (+9 each) and each orthogonal non-citation corroboration line (+6 each: Wikipedia, clinical trials, open datasets or software, public funding, community discussion). Capped at 100.5 of 5 citation indices agree, 1 independent non-citation line790.3023.7OpenAlex, Crossref, Semantic Scholar, OpenCitations, Europe PMC, DataCite, NIH RePORTER, Wikipedia, Hacker News count of agreeing indices + orthogonal reach
VerifiabilityHow openly the result can be read, reused, and reproduced. Rewards open access, a permissive reuse license (CC-BY/CC0), a green repository copy anyone can archive, openly minable full text, and released datasets or software a reader can actually run. Cross-checked across OpenAlex, Unpaywall, Europe PMC, and DataCite.Maps to 0 to 100: Closed 45; open access 80+; a permissive CC license 100; a repository copy, open full text, or a released dataset/software artifact each raise the floor.Closed access450.209.0OpenAlex, Unpaywall, Europe PMC, DataCite is_oa / license / has_repository_copy / open datasets
IntegrityRetraction and post-publication correction status. A retracted result is not evidence of anything and collapses the whole Frontier Score; a correction or expression of concern is a softer flag. Read across OpenAlex and Crossref (both update-to and updated-by notices).Maps to 0 to 100: Clean 100; a correction or expression of concern 75; retracted 0. Flagged if OpenAlex OR Crossref records the notice.No retraction or concern on record1000.2020.0OpenAlex, Crossref is_retracted / update-to / updated-by
Impact88
Impact sub-metrics
Sub-metricRaw value0 to 100WeightPointsSource
Field-normalized impactImpact relative to the world average for the same field, year, and type, so a small field and a large field are judged fairly. Triangulates three independent field-normalized measures: OpenAlex's Field-Weighted Citation Impact, its citation percentile within the exact field-and-year cohort, and the NIH iCite Relative Citation Ratio. 1.0x is average; the percentile is the share of same-field, same-year work it out-cites.Maps to 0 to 100: Each ratio (1.0 = field average) maps 1.0 to 50, 3.0 to 75, 9.0 to 90; the field+year percentile maps directly (top 1% -> ~99). The available measures are averaged. Falls back to a saturating citation count when none is available yet.86.2x FWCI, 32.1x RCR, top 0.0% of field-year vs field990.4544.4OpenAlex, NIH iCite fwci / citation_normalized_percentile / relative_citation_ratio
Influential citationsCitations that genuinely build on the work rather than mention it in passing (Semantic Scholar's influential-citation measure). A sharper signal of real impact than a raw count.Maps to 0 to 100: Saturating: 15 influential citations maps to 50. Falls back to a fraction of consensus citations when unavailable.23 influential610.2012.1Semantic Scholar influentialCitationCount
Citation velocityCitations received in the trailing twelve months, judged as a rate rather than a lifetime total. Momentum is what a frontier index cares about: a result being taken up fast right now is landing, whether its lifetime pile is large or still small. Where an expected field citation rate is known, the momentum is also read relative to it, so a fast-moving result in a quiet field is not overlooked.Maps to 0 to 100: Saturating: 30 citations in the last twelve months maps to 50. When NIH iCite provides the field's expected rate, this is blended evenly with the ratio of observed to expected momentum.154 in last 12 months (18.4x field rate)890.3531.3OpenAlex, NIH iCite counts_by_year / field_citation_rate
Novelty46
Novelty sub-metrics
Sub-metricRaw value0 to 100WeightPointsSource
Conceptual noveltyHow genuinely new the contribution is, measured at publication from the work's OWN content, not its date: how atypical its combination of research areas is versus all prior work, and whether it builds on a broad, deep base rather than only the newest papers in a fast-moving area. This is what separates a real advance from a recent-but-commodity result, and it needs no forward citations, so it is stable for brand-new work. An honestly noisy proxy (even state-of-the-art novelty measures agree only moderately with expert judgment), so it carries bounded weight and never drives the ranking alone.Maps to 0 to 100: Blends two publication-time signals, each 0-100: an atypical-combination score (how unusual the pairing of the work's research topics is versus the prior literature, by pointwise mutual information) and a foundational-reach score (median age and depth of the work's references). The stronger signal weighs 0.62, the weaker 0.38. When neither is measurable (a work too thin in topics or references), the pillar renormalizes over its recency signals instead.Bariatric Surgery and Outcomes x Pharmacology and Obesity Treatment (4,860 prior works made this pairing); builds on refs a median 2.2y deep260.4511.6OpenAlex topics + referenced_works (publication-time)
RecencyHow recently the work appeared. The frontier is now, so newer scores higher.Maps to 0 to 100: Exponential decay with a 12-month half-life from the publication date.12 months old490.3014.6OpenAlex publication_date
Attention accelerationWhether attention is rising: citations in the latest full year versus the year before. Accelerating interest signals an active, opening frontier.Maps to 0 to 100: Latest/prior-year ratio: 1x maps to 50, 2x to 75, 4x to 100. Unknown is neutral.4.0x rising1000.1010.0OpenAlex counts_by_year
Edge of reviewPreprints and brand-new work sit ahead of the peer-review process. That earns novelty here (while it is discounted under Evidence), because it is where the frontier forms first.Maps to 0 to 100: Preprint 95, article <6 months 80, article <18 months 65, else 45.Peer-reviewed record650.159.8OpenAlex type / publication_date
ProvenanceAll sources

Sources and data

Every number behind this entry, grouped by the source that holds it: up to five citation indices cross-checked, field-normalized impact, then real-world reach (Wikipedia, community discussion, clinical trials, released data and public funding) where it exists. Each value links to its record.

OpenAlex

Primary record
Total citations
163
Field-weighted citation impact
86.2x field average
Citation percentile
Top 0.1% of its field-year
Citations, recent 12 months
154
Publication date
2025-09-16

Crossref

Citations
170
Works it builds on
27
Funders on record
1

Semantic Scholar

Citations, all versions
127
Influential citations
23

OpenCitations

Citations
30

Europe PMC

Citations
65

NIH iCite

Relative Citation Ratio
32.08x field average
Potential to translate
95%
Cited by clinical articles
12

ClinicalTrials.gov

Registered clinical trials
1 (to phase 3)

Figures quoted in the write-up

FigureValueSource
Weight change, 36 mg dose (Mean change from baseline to week 72)-11.2%New England Journal of Medicine
Weight change, placebo (Mean change over same period)-2.1%New England Journal of Medicine
Lost 10%+ body weight (36 mg) (vs 12.9% on placebo)54.6%New England Journal of Medicine
Lost 20%+ body weight (36 mg) (vs 2.8% on placebo)18.4%New England Journal of Medicine
Patients randomized (Multinational, double-blind)3,127New England Journal of Medicine
Trial duration (Adjunct to diet and activity)72 weeksNew England Journal of Medicine
Biomedicine & HealthThe whole field

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