Five selected reports cover early oral and subcutaneous amycretin studies, later phase 2 diabetes reports using the name zenagamtide, and a renal-function pharmacokinetic study. The two phase 2 reports describe separate route cohorts within one registered protocol.12345
Bottom line from this bounded source set
Early trials reported weight reductions but were designed primarily to assess safety and tolerability. Later zenagamtide studies reported improved glycated hemoglobin in type 2 diabetes. Gastrointestinal adverse events and study discontinuations matter when interpreting these findings.1234
Reviewed study record
Oral amycretin: first-in-human study
Design
A blinded randomized placebo-controlled phase 1 study contained several escalating-exposure parts.1
Population
The study enrolled 144 adults with overweight or obesity across its parts.1
Outcomes reported
Treatment-emergent adverse events were reported in 89 participants and were mild or moderate; gastrointestinal events were common.1
Limitations
Safety was the primary endpoint; weight-related measures were exploratory. Small cohorts and short follow-up do not establish long-term clinical benefit or safety.1
Reviewed study record
Subcutaneous amycretin: phase 1b/2a study
Design
A randomized placebo-controlled multipart study assessed safety and secondary body-weight changes over up to 36 weeks.2
Population
The study randomized 125 adults with overweight or obesity at one research center.2
Outcomes reported
Estimated weight reductions were greater with amycretin. Gastrointestinal events were common, and the authors reported many study withdrawals.2
Limitations
Primary endpoints concerned adverse events. Small cohorts, different observation lengths and substantial attrition limit comparisons and interpretation of weight estimates.2
Reviewed study record
Oral zenagamtide: phase 2 diabetes cohort
Design
A blinded randomized placebo-controlled study assessed 36-week glycated hemoglobin change under NCT06542874.3
Population
This report included 186 adults with type 2 diabetes receiving metformin with or without an SGLT2 inhibitor.3
Outcomes reported
All three active groups improved glycated hemoglobin compared with placebo. Gastrointestinal events were common; seven participants in active groups had serious adverse events.3
Limitations
The primary analysis used on-treatment data without rescue medication. Glycemic improvement does not establish reduction in long-term complications; this cohort shares a protocol with the subcutaneous report.3
Reviewed study record
Subcutaneous zenagamtide: phase 2 diabetes cohort
Design
A blinded randomized placebo-controlled study assessed 36-week glycated hemoglobin change under NCT06542874.4
Population
This route cohort randomized 262 adults with type 2 diabetes; 261 received treatment.4
Outcomes reported
Active groups improved glycated hemoglobin compared with placebo. Gastrointestinal adverse events were common; serious adverse events were reported in active and placebo groups.4
Limitations
This is a route cohort within the same protocol as the oral report, not evidence from an unrelated replication. Follow-up and surrogate endpoints limit conclusions about long-term outcomes.4
Reviewed study record
Renal-function pharmacokinetic study
Design
A single-exposure study compared pharmacokinetics across renal-function groups with four weeks of follow-up, registered as NCT06559527.5
Population
Forty-two adults participated: 14 with normal renal function and seven each with mild, moderate or severe impairment or end-stage renal disease.5
Outcomes reported
The authors reported broadly comparable exposure measurements across groups. Treatment-emergent adverse events occurred in 30 of 42 participants; none were serious or severe, and most were mild gastrointestinal events.5
Limitations
Small groups, one exposure and short follow-up do not establish long-term safety or therapeutic benefit in people with kidney disease. The report does not support individualized treatment recommendations.5
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1016/s0140-6736(25)01176-6. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1016/s0140-6736(25)01185-7. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1016/s0140-6736(26)01247-x. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1016/s0140-6736(26)01248-1. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1111/dom.71096. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗