Similar studies

An observational atlas linked GLP-1 receptor agonists to dozens of outcomes beyond glucose, weight and the heart. We pooled the serious adverse events that 234 placebo-controlled trials, with 161309 participants, posted to ClinicalTrials.gov, coded blind to the results under a registered plan. Reports of serious bacterial infection (ratio 0.88, confidence interval 0.83 to 0.93) and pneumonia (0.87) were less frequent on the drugs, as were pneumonia counted in people and death. The reductions held under random effects, with any trial left out, if infection terms overlapped within participants as all serious events do in each comparison, and in trials not coded as recording only on treatment. Of the atlas's associations with enough events to test, the trials found three in its direction with no difference from it detected, contradicted none, and left most inconclusive, among them every neurological and psychiatric one; its large hazard of drug-induced pancreatitis concerns a subtype the trials don't separate.

• Published, Reproduced.Published, Reproduced: Of the 539 interventional studies of GLP-1 receptor agonists with results on ClinicalTrials.gov on 2026-10-12, 234 randomized trials compare a GLP-1 receptor agonist with placebo, in 257 comparisons with 161,309 participants in their adverse-event tables (93,765 on the drugs and 67,544 on placebo). In them, reports of serious gallbladder and biliary disease, counting a participant once for each of the outcome's terms they had, are more frequent on the drugs (Mantel-Haenszel ratio 1.38, 95% CI 1.21 to 1.57), and so are reports of serious nausea and vomiting (2.02, 1.52 to 2.68), as the trials' own publications and the drugs' labels lead one to expect.
• Published, Reproduced.Published, Reproduced: Reports of serious bacterial infection, counting a participant once for each of the outcome's terms they had, are less frequent on GLP-1 receptor agonists in these trials (2,409 among 93,765 participants against 2,532 among 67,544 on placebo; Mantel-Haenszel ratio 0.88, 95% CI 0.83 to 0.93, q < 0.001), and so are reports of serious pneumonia (1,442 against 1,568; 0.87, 0.81 to 0.93, q = 0.0020); both stay significant under random effects and with any single trial left out. Counted in participants, pneumonia under its own preferred term, which no group reports in more than one row, is less frequent (807 against 880; 0.86, 0.79 to 0.95). If infection terms overlapped within a participant as all serious terms do in the same arm of the same comparison, bacterial infection would be 0.89 (0.82 to 0.97).
• Published, Reproduced.Published, Reproduced: In the registered scan without hypotheses of 27 organ systems and 518 preferred terms, with the same variance as the other claims, four organ systems (cardiac disorders; infections and infestations; metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders) and two preferred terms (acute myocardial infarction and cellulitis) are lower on the drugs with q < 0.05 in a random half of the trials and p < 0.05 in the held-out half, and one organ system, hepatobiliary disorders, is higher (1.36 in the first half, 1.24 in the second), as the gallbladder positive control leads one to expect. Among those lower are serious infection reports as a whole (0.88 and 0.89) and cellulitis (0.64 and 0.75); cardiac disorders and myocardial infarction are events many trials record as adjudicated end points rather than in these tables.

6 more claims

Whether antidepressants raise suicidal behaviour in adults is disputed: the FDA's pooled trials found no increase past young adulthood, and re-analyses of approval data on newer drugs found more suicide attempts. We tested this in the serious adverse events placebo-controlled trials posted to ClinicalTrials.gov, under a registered plan. This version corrects the first, which counted a participant listed under two of an outcome's terms twice. With the posted tables and the trials' public reports, serious suicidal behaviour affected 43 adults on antidepressants and 17 to 18 on placebo (risk ratio 1.86 to 1.96): nominally significant, but at the least favourable count not after the registered correction for two endpoints. Without the trials the re-analyses also used, the excess is similar but less certain. Pediatric trials showed more serious suicidality on antidepressants, as the FDA found. These data lean toward more suicidal behaviour in adults but cannot establish it.

• Published, Reproduced.Published, Reproduced: Of the 932 interventional studies naming an antidepressant with results posted on ClinicalTrials.gov on 2026-10-13, 393 randomized trials compare an antidepressant with placebo in 413 comparisons with 99,730 participants at risk in their adverse-event tables. In the 306 adult trials that randomized participants from the start (71,643 participants), nausea is more frequent on antidepressants in the 207 comparisons whose non-serious tables list it (57,580 participants; Mantel-Haenszel risk ratio 2.08, 95% CI 1.98 to 2.18), as these drugs' known side effects predict.

Evidence that small fMRI studies overstate effects comes mostly from reported peaks, which are inflated by selection whatever the sample size. We asked the question with a whole-brain measure that has no peak selection. For each published (DOI-linked), group-level, unthresholded task-fMRI T or Z map on NeuroVault (Gorgolewski et al. 2015), we estimated the root-mean-square standardized effect over a fixed grey-matter mask from the mean squared statistic. We then regressed its log on log N with map-type, smoothing, upload-year and paradigm fixed effects plus a random intercept per collection. Everything was preregistered (prereg:f7ecdaf6…) on a frozen map list. After QC and de-duplication, 1245 maps from 200 collections were analysed. The slope was β = -0.101387 (CI -0.272087 to 0.069313), so the locked decision is inconclusive. There is no significant small-study inflation, and steep slopes are excluded. The data cannot rule out a modest slope at the preregistered boundary.

• Published, Reproduced.Published, Reproduced: Across 1,245 QC-passing, de-duplicated, published (DOI-linked) group-level unthresholded task-fMRI T/Z maps from 200 NeuroVault collections (N 10–1,369), the preregistered mixed model of log whole-brain rms standardized effect (grey-matter mask) on log N gives beta = -0.101387 (95% CI -0.272087 to 0.069313): no statistically significant small-study inflation of whole-brain effect sizes; slopes steeper than about -0.27 are excluded, but the preregistered refutation bound (-0.10) is not, so the locked decision is inconclusive.

An account of depression as accumulated physical load distributed across body systems predicts that each system's state tracks the symptoms it produces, that bodily measures relate to somatic symptoms beyond mood, and that socially distributed load appears somatically. We tested these predictions in a registered analysis of 14722 adults in the US National Health and Nutrition Examination Survey (NHANES), relating limitation in load-bearing tasks, slow bowel transit, body mass index (BMI), an allostatic load index and income to PHQ-9 depressive symptom items. Load-bearing limitation, BMI and allostatic load related to somatic symptoms beyond cognitive-affective ones, and more than to cognitive-affective symptoms beyond somatic ones. But the predicted system-specific pattern did not appear: load-bearing limitation tracked sleep, energy and appetite (0.2946) far more than slow transit did (0.0404). Low income related more to cognitive-affective than to somatic symptoms (difference -0.0996). Bodily load is linked to somatic depression generally, not system by system.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: In 14722 NHANES 2005-2010 adults, limitation in load-bearing tasks is associated with the PHQ-9 psychomotor item more than slow bowel transit is (age-, sex- and cycle-adjusted partial Spearman 0.2038 vs 0.0296), but also with the sleep, energy and appetite items more than slow transit is (0.2946 vs 0.0404; difference -0.2542, 95% CI -0.2762 to -0.2312), so the predicted double dissociation between a structural and a transport system does not appear.

How often do stars like the Sun release superflares of $10^{34}$ erg or more? A recent Kepler analysis found once per century, far more often than earlier ones. We tested this with TESS: a pre-registered search of the two-minute light curves of 32908 stars selected as that analysis selected its Sun-like stars, with flares of known energy injected into every light curve to measure what it finds. It counted 78 superflares where the once-per-century rate predicts 23.4: 3.33 times that rate (interval 2.63 to 4.15), one per 33 years per star, far above the earlier rates. Every planned subset and sensitivity analysis gives a ratio above one. An exploratory emulation of the Kepler search suggests its correction for missed flares, measured with the profile it injected, understates the rate of flares shaped as assumed here by a factor of 1.79 between $10^{34}$ and $10^{35}$ erg; its published rates don't follow from its own figures, so how much of the gap is Kepler's remains open. All of it rests on the stars selected and the flare energies and shapes assumed.

• Published.Published: In 94,747 TESS 2-minute light curves of 32,908 stars of 5000 to 6500 K with absolute G magnitudes of 4 to 6 and RUWE below 1.4 (5,605 star-years), the pre-registered search, with its SAP test corrected after registration to require the uncorrected flux to rise, counted 78 flares of bolometric energy 10^34 erg or more where the rate Vasilyev et al. (2024) measured with Kepler predicts 23.4 under the search's measured completeness and the assumed flare durations: 3.33 times that rate (95% CI 2.63 to 4.15), about once per 33 years per star; the registered code counted 79 (3.37 times, 2.67 to 4.20).