985-P: Oral Semaglutide as Add-On to Insulin in T2D: PIONEER 8
Bibliographic record
Abstract
Patients (pts) with T2D uncontrolled on insulin ± metformin were randomized to oral semaglutide (sema) 3 mg (N=184), 7 mg (N=182) or 14 mg (N=181), or placebo (pbo; N=184) in a 52-week (week) double-blind trial (NCT03021187). Total daily insulin dose was reduced by an optional 20% and capped at baseline (BL) level for week 0-26 and freely adjustable for week 26-52. Endpoints were change from BL to week 26 in HbA1c (primary) and body weight (BW; confirmatory secondary). Two scientific questions were addressed by defining two estimands: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use), and a trial product estimand (on trial product without rescue medication use) in all randomized pts. Oral sema was superior to pbo in reducing HbA1c and BW at week 26 (treatment policy estimand). Significantly greater, dose-dependent HbA1c and BW reductions vs. pbo were achieved at week 26 and 52 (both estimands; Table). Total daily insulin dose was significantly reduced from BL with oral sema vs. pbo at week 26 (except 3 mg) and 52. The rate of hypoglycemia was not significantly different vs. pbo (Table). Most frequent AE with oral sema was nausea (11.4-23.2% of pts vs. 7.1% with pbo) and 7.1-13.3% of pts prematurely discontinued due to AEs (vs. 2.7% with pbo). As add-on to insulin ± metformin, oral sema had superior HbA1c and BW reductions vs. pbo at week 26. It also reduced insulin use by week 52 and was well tolerated without significantly increasing hypoglycemia rate. Disclosure B. Zinman: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. V.R. Aroda: Consultant; Self; ADOCIA, AstraZeneca, Becton, Dickinson and Company, Novo Nordisk Inc., Sanofi, Zafgen, Inc. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; AstraZeneca, Calibra Medical, Eisai Inc., Janssen Research & Development, Novo Nordisk Inc., Sanofi, Theracos, Inc. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc. B. Cariou: Board Member; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals. Consultant; Self; GENFIT, Sanofi-Aventis. Research Support; Self; Amgen Inc., Pfizer Inc. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Merck Sharp & Dohme Corp. S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. S.T. Hoff: Employee; Self; Novo Nordisk A/S. K. Pedersen: Employee; Self; Novo Nordisk A/S. M. Tarp-Johansen: Employee; Self; Novo Nordisk A/S. E. Araki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Novo Nordisk Inc., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi. Funding Novo Nordisk A/S
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".