MedicinemedRxiv
Ranked by formulaVerdict: NotableImmune Training with BCG therapy in Diabetes: Outcomes of a Phase 2 randomized clinical trial
BCG is a well recognized old generic drug that can mold the human immune system through Immune Training.
Key numbers
- 183.7% improvement over baseline in
Caveats
- Preprint; not yet peer reviewed.
VerdictWorth a reader's time today.
Abstract
BCG is a well recognized old generic drug that can mold the human immune system through Immune Training. Broad basic science studies support Immune Training, but formal randomized placebo control trials are frequently lacking for confirmation of human benefits. Here we report on a randomized, double-blind, placebo-controlled phase 2 trial with up to 8 years of follow-up. The primary outcome was mean percent change from baseline in HbA1c. At year 5, HbA1c in the BCG group was reduced from baseline by 7.04% (P=0.0006) and at year 8 by 12.84% (P=0.0001), whereas HbA1c did not change from baseline in the placebo group at either time point. Longitudinal percentage changes in HbA1c from baseline using mixed model repeated measures analysis with a comparison of BCG versus Placebo arms was significant (p=0.0017). This shows durable long term improvements lowering of HbA1c only with BCG immunotherapy. Secondary outcomes were also significant. There was a statistically significant reduction in average insulin dose only in the BCG-treated group (P=0.024). Glycemic improvements occurred without recovery of C-peptide from negligible baseline levels, suggesting no pancreas contribution. Blood sugar values obtained from continuous glucose monitoring (CGM) similarly showed BCG immunotherapy lowers blood sugars compared to the Placebo arm (P=0.0189). CGM data also showed BCG immunotherapy resulted in an up to 183.7% improvement over baseline in time spent in normoglycemia (blood sugar in the normal range of 70-99 mg/dL) (P=0.0391). A sensitivity analysis confirmed BCG specific reductions in HbA1c were robust and durable at least to Year 08 (P<0.0001). BCG was safe. These finding support improved blood sugar control through immune training of metabolism without a contribution of the pancreas even after long standing T1D. Trial registration: NCT02081326.
The editor's rubric
| Dimension | Level | Weight | What that level means |
|---|---|---|---|
| Leverage | ███░░ 3 | 10% | A method or resource many groups across the field will adopt within a year. |
| Magnitude | ███░░ 3 | 20% | Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem. |
| Evidence | ████░ 4 | 32% | Strong: large scale, preregistered, independently replicated, or a well-powered randomized trial. |
| Novelty | ██░░░ 2 | 8% | A new combination of known ideas. |
| Trajectory | ██░░░ 2 | 5% | Some room to improve with obvious engineering. |
| Stakes | ███░░ 3 | 25% | Meaningful benefit to many people within a few years. |
Editor’s rationale
Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: method (we report); gains (relative gain); novelty (open problem); design (randomized, blinded, placebo-controlled); verification (p-value, independent replication); stakes (major disease, prevention or cure). Red flags: derivative (comparative study).
How the score was computed
- Merit
- 6.4 / 10
- Adjusted merit
- 5.2 / 10
- Attention
- 0%
- Freshness
- 92%
- Citations0 (reference 20, via semantic-scholar, Oct 14, 2026, 06:17 UTC)