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Dnu3.5
Danuglipron Research
Mostly mechanism / observationalLimited safety
6 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Danuglipron studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2021–2025 with a typical study size of 411 participants.
Based on 6 studies · 1 meta-analysis · 4 RCTs · 1,288 total participants
Confidence
Moderate
By outcome
Glucose & glycemic control
Mostly mechanism / observational5 studies
Safety & tolerability
Mostly mechanism / observational5 studies
Weight & obesity
Mostly mechanism / observational4 studies
Active research area
6 studies in the last 5 years · Latest meta-analysis: 2023
20212025
1RCTn=411 · medium study2023
For all danuglipron doses, HbA1c and FPG were statistically significantly reduced at week 16 vs placebo, with HbA1c reductions up to a least squares mean difference vs placebo of -1.16%... for the 120-mg twice daily group... Body weight was statistically significantly reduced... -4.17 kg... for the 120-mg twice daily group.
Saxena AR, Frias JP, Brown LS, Gorman DN, Vasas S, Tsamandouras N, Birnbaum MJ. · JAMA Netw Open (2023)
Phase-2b double-blind, placebo-controlled RCT (n=411) in adults with type 2 diabetes; twice-daily oral danuglipron 2.5/10/40/80/120 mg vs placebo over 16 weeks with weekly dose escalation
Dose-dependent HbA1c reduction up to a placebo-adjusted -1.16% and fasting-glucose reduction up to -33.24 mg/dL at 120 mg BID
Body weight significantly reduced at the 80 mg (-2.04 kg) and 120 mg (-4.17 kg) doses vs placebo; 77% completed treatment
all danuglipron groups demonstrated statistically significant reductions with least squares mean percentage decreases from baseline ranging from -5.0%... to -12.9%... relative to placebo... Approximately 38% of participants discontinued treatment because of adverse events.
Buckeridge C, Cobain S, Bays HE, Matsuoka O, Fukushima Y, Halstead P, Tsamandouras N, Sherry N, Gorman DN, Saxena AR. · Diabetes Obes Metab (2025)
Phase-2b double-blind, placebo-controlled, dose-ranging RCT (n=628) in adults with obesity WITHOUT diabetes; twice-daily oral danuglipron 40-200 mg over 26 or 32 weeks
Placebo-adjusted weight loss ranged from -5.0% to -12.9% — clinically meaningful across all danuglipron groups
Only 39.3% completed treatment; ~38% discontinued for adverse events (mainly nausea and vomiting), unusually high attrition
Discontinuation from study medication occurred in 27.3% to 72.7% of participants across danuglipron groups versus 16.7% to 18.8% for placebo, most often due to adverse events.
Saxena AR, Frias JP, Gorman DN, Lopez RN, Andrawis N, Tsamandouras N, Birnbaum MJ. · Diabetes Obes Metab (2023)
Phase-2a double-blind, placebo-controlled RCT (n=151; T2D and obesity arms) comparing dose-escalation schemes of twice-daily danuglipron up to 200 mg BID over 12 weeks
HbA1c fell -1.04% to -1.57% (vs -0.32% placebo) and body weight -1.93 to -5.38 kg (vs -0.42 kg placebo) in T2D
Discontinuation was 27.3%-72.7% across danuglipron groups (vs 16.7%-18.8% placebo), most often from GI adverse events that tracked target dose not starting dose
In this study in T2D, danuglipron was generally well tolerated, with a safety profile consistent with the mechanism of action of GLP-1R agonism.
Saxena AR, Gorman DN, Esquejo RM, Bergman A, Chidsey K, Buckeridge C, Griffith DA, Kim AM. · Nat Med (2021)
Phase-1 multiple-ascending-dose, double-blind, placebo-controlled RCT (n=98) in type 2 diabetes on background metformin; danuglipron vs placebo over 28 days across eight cohorts
Primary outcomes were safety (adverse events, labs, vitals, ECG); most adverse events were mild, with nausea, dyspepsia and vomiting most common
Heart rate generally increased and systolic BP slightly decreased; no clinically meaningful lab or ECG findings
Novel GLP-1RAs led to significant reduction in HbA1c... (MD = -1.03%)... and significantly higher odds of gastrointestinal, treatment-emergent adverse events (OR = 2.57...) and adverse events leading to discontinuation (OR = 2.89...).
Karakasis P, Patoulias D, Pamporis K, Stachteas P, Bougioukas KI, Klisic A, Fragakis N, Rizzo M. · Metabolism (2023)
Systematic review and random-effects meta-analysis of 7 RCTs (n=1037) of the oral small-molecule GLP-1 agonists orforglipron and danuglipron in T2D and/or obesity
Significant HbA1c reduction (-1.03%) and weight reduction (-3.26 kg in T2D; -7.52 kg in obesity) vs controls; all RCTs low risk of bias (RoB2)
Neutral on severe hypoglycemia and serious adverse events, but ~2.57x higher GI adverse events and ~2.89x higher discontinuation vs controls
Herein, we describe the discovery of the orally bioavailable, small-molecule, GLP-1R agonist PF-06882961 (danuglipron)... a binding pocket requiring a primate-specific tryptophan 33 residue.
Griffith DA, Edmonds DJ, Fortin JP, Kalgutkar AS, Kuzmiski JB, Loria PM, Saxena AR, et al. · J Med Chem (2022)
Discovery and medicinal-chemistry paper for PF-06882961 (danuglipron): a 5-fluoropyrimidine chemotype optimized from a sensitized high-throughput screen
A cryo-EM structure and mutagenesis revealed a binding pocket requiring a primate-specific tryptophan-33 residue — explaining insulin increases in primates but not rodents
First single oral dose in healthy humans produced dose-proportional systemic exposure (NCT03309241)