Effects of <scp>CB1R</scp> inverse agonist, <scp>INV</scp> ‐202, in patients with features of metabolic syndrome. A randomized, placebo‐controlled, double‐blind phase 1b study
Bibliographic record
Abstract
Abstract Aims To evaluate the clinical safety, tolerability, and pharmacokinetic and pharmacodynamic profile of the novel cannabinoid receptor‐1 (CB1R) inverse agonist, INV‐202, in adults with features of metabolic syndrome. Materials and Methods This was a multicentre, randomized, double‐blind, placebo‐controlled, 28‐day repeat‐dose (INV‐202 [25 mg] or placebo, once‐daily oral tablet), parallel‐group study in 37 participants aged 18 to 65 years (46% female, mean age 55 years, glycated haemoglobin 5.7% [39 mmol/mol], body mass index [BMI] 38.1 kg/m 2 ) with features of metabolic syndrome and glucose intolerance. An oral glucose tolerance test (OGTT) was performed at baseline and at the end of the study. Lipid profiles, weight, waist circumference and biomarkers were assessed weekly. Statistical comparisons were performed post hoc. Results INV‐202 was well tolerated with no serious or severe treatment‐emergent adverse events; the most common events related to known effects of CB1R blockade in the gastrointestinal tract. INV‐202 produced a significant mean weight loss of 3.5 kg (3.3% compared with placebo participants who gained a mean 0.6 kg [0.5%]). INV‐202 also exhibited significant reductions in waist circumference and BMI ( P ≤ 0.03). There was no significant difference in OGTT 0‐ to 3‐hour area under the curve for INV‐202 versus placebo: least squares mean 29.38 versus 30.25 h*mmol/L, with an INV‐202: placebo ratio of 97.1% (95% confidence interval 90.2, 105.6; P = 0.43). Conclusions INV‐202 was well tolerated, producing a signal for rapid weight loss with improvements in other metabolic syndrome markers in this population. These findings support further exploration and long‐term assessment of cardiometabolic effects.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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".