N=566
Treated
Naive to the drug
Naive to the drug
Clinical Pearls · 2026
Metabolic and Prolactin Outcomes After 52 Weeks of Xanomeline-Trospium
EMERGENT-5
52
Weeks
Open-label
Open-label
228.1
Days mean exposure
About 33 weeks
About 33 weeks
48.9%
Completed
51.1% discontinued
51.1% discontinued
−2.2kg
Mean weight change
At week 52
At week 52
−2.5µg/L
Mean prolactin change
At week 52
At week 52
The question:Weight, lipids and prolactin are monitored during long-term antipsychotic treatment. What did 52 weeks of xanomeline-trospium show across these measures?
About the trial. EMERGENT-5 was open-label and single-arm, with no placebo or active comparator. Laboratory and safety outcomes were reported descriptively and no formal statistical testing was performed, so no P values or confidence intervals exist for any value shown.
Participants Above Each Laboratory Threshold
Baseline n = 557 to 566; week 52 n = 269 to 277
Laboratory threshold
Baseline
Week 52
Difference
Total cholesterol >200 mg/dL
35.3%
31.0%
−4.3%
Triglycerides ≥150 mg/dL
16.4%
12.3%
−4.1%
Glucose ≥100 mg/dL
5.1%
7.6%
+2.5%
HbA1c >7%
5.0%
4.5%
−0.5%
The week-52 denominators are smaller because 51.1% of participants discontinued before week 52. The difference column therefore compares two cross-sectional proportions rather than a within-participant change. These descriptive findings do not establish a treatment effect.
Weight Change
Mean changes at week 52
26.4% lost
≥7%
≥7%
Of body weight
146 of 554
6.9% gained
≥7%
≥7%
Of body weight
38 of 554
−2.2 kg
Mean weight change
SD 6.3
−0.7
Mean BMI change
SD 2.1
Baseline weight 88.7 kg and BMI 29.8 kg/m². The ≥7% figures represent changes occurring at any point after baseline, not necessarily at week 52, and were calculated for the 554 participants with a post-baseline weight. Nausea and vomiting were the most common treatment-emergent events, at 23.1% and 20.3%, and the trial did not test whether the weight change reflects a metabolic effect of treatment or gastrointestinal intolerance.
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Clinical Pearls · 2026
Prolactin, Motor Symptoms and Adverse Events
Prolactin, movement scales and treatment-emergent events over 52 weeks. N=566.
Prolactin
No baseline prolactin value and no proportion above the upper limit of normal were reported
−2.5 µg/L
Mean change to week 52
SD 11.8 µg/L
3 of 566
Increased prolactin, as an event
0.5%
5
Post-baseline sampling visits
Weeks 4, 16, 24, 40, 52
Mean prolactin did not increase over 52 weeks. The SD of 11.8 µg/L is larger than the mean change itself, so the group mean does not exclude increases in individual participants. Without a reported baseline, the change cannot be judged against a starting level. The single-arm design does not establish a prolactin-lowering treatment effect.
Treatment-Related Metabolic, Lipid and Prolactin Events
N = 566
Event
Participants
Proportion
Increased prolactin
3
0.5%
Increased HbA1c
3
0.5%
Decreased HDL
1
0.2%
Hypertriglyceridemia
1
0.2%
This panel covers metabolic, lipid and prolactin events only. It is not the trial's overall adverse-event profile.
Movement Scale Changes and EPS Events
Over 52 weeks, N=566
Movement scale
Mean (SD)
Simpson-Angus Scale
−0.3 (1.0)
Barnes Akathisia Scale
−0.2 (1.0)
Abnormal Involuntary Movement Scale
−0.1 (0.8)
EPS event
Participants
Akathisia
7
Tardive dyskinesia
2
Dyskinesia
1
Mean movement-scale scores changed little over 52 weeks, by 0.3 points or less against SDs of 0.8 to 1.0, and the uncontrolled design does not permit attribution of these changes to treatment.
Adverse Events and Discontinuation
N = 566
82.3%
Had at least one treatment-emergent adverse event
23.1%
Nausea
Most common event
20.3%
Vomiting
Second most common
18.0%
Constipation
Third most common
Adverse events were the most common reason for discontinuation, at 17.0% of the cohort, followed by withdrawn consent at 16.4%. The three shown are the most frequently reported; this section reports event frequency, not the full safety profile or the adverse reactions in the approved labeling.
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Clinical Pearls · 2026
Findings, Design Limits and Sources
What the trial observed, what its design cannot establish, and the cited sources.
What the Data Show
As observed, not as established
Metabolic measures moved in both directions
Cholesterol, triglyceride and HbA1c proportions above threshold were lower at week 52. The proportion with glucose ≥100 mg/dL rose from 5.1% to 7.6%.
Weight decreased on average
Mean change −2.2 kg from a baseline of 88.7 kg. 26.4% lost ≥7% and 6.9% gained ≥7% at any point after baseline. The direction cannot be attributed to a metabolic effect of treatment.
Mean prolactin did not increase
Mean change −2.5 µg/L with an SD of 11.8 µg/L, and increased prolactin was reported as an event in 3 of 566. No baseline value and no proportion above the upper limit of normal were reported.
Movement-scale changes were small
Mean changes of 0.3 points or less against SDs of 0.8 to 1.0. Akathisia in 7 participants, tardive dyskinesia in 2 and dyskinesia in 1.
What the Data Cannot Show
Design limits
Direction, not cause
No value shown establishes a treatment effect, and none establishes that xanomeline-trospium is metabolically superior to other antipsychotics. The trial can show which way a measure moved, not why.
Half the cohort did not reach week 52
51.1% discontinued before week 52 and 277 completed the treatment period, so the week-52 laboratory proportions reflect 269 to 277 participants. No week-52 n was reported for weight, prolactin or the movement scales. Mean exposure was 228.1 days, about 33 weeks, against a nominal 52. Differential dropout may account for part of the observed direction.
Two explanations are not separable
Every participant entered from prior antipsychotic treatment, so withdrawal of a previous agent may account for part of the change. Nausea and vomiting were the trial's most common treatment-emergent events, so weight loss may reflect gastrointestinal intolerance. Neither explanation was tested, and the single-arm design offers no way to weigh one against the other.
Clinical pearl
Among adults with schizophrenia who remained on xanomeline-trospium for 52 weeks, group-level weight, lipid and prolactin measures did not worsen, and the proportion with glucose ≥100 mg/dL rose from 5.1% to 7.6%. Because the trial had no comparator and no statistical testing, this describes what happened in one cohort rather than a metabolic advantage over other agents, and it describes only the participants who completed.
Sources and Disclosures
Financial support. Financial support was provided by Bristol Myers Squibb. Psychiatrist.com independently developed the content and maintained final editorial control.
EMERGENT-5 analysis. Every figure in this summary is an observed proportion or mean carried over from the source without further analysis. Safety observations are limited to 52 weeks of open-label treatment in adults with schizophrenia. The authors of the cited trial include employees and consultants of the manufacturer of xanomeline-trospium.
Regulatory status. Xanomeline-trospium is approved for the treatment of schizophrenia in adults. The trials supporting that approval were 5 weeks in duration, and the approved labeling does not address weight, lipids, glucose, HbA1c or prolactin. Consult the full prescribing information for the approved use, the warnings and precautions, and the complete safety profile.
Sources: Kaul I, Claxton A, Chaturvedi S, Patel T, Wu H, Sawchak S, Sauder C. Long-term efficacy, safety and tolerability of xanomeline and trospium chloride in schizophrenia: a 52-week, open-label trial (EMERGENT-5). Schizophr Res. 2026;288:86–94 (NCT04820309). US prescribing information for xanomeline and trospium chloride capsules, which supports the regulatory status statement. Review the original sources for full detail.
This "Clinical Pearls" summary is based on the cited sources and is not intended to replace independent medical judgment or individualized patient care. © 2026 Physicians Postgraduate Press, Inc.
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