Century-Old BCG Tuberculosis Vaccine Shows Promise in Reducing Insulin Use in Type 1 and LADA Diabetes
Key Insights
Two phase II trials show the BCG vaccine reduced insulin use and improved blood sugar control in people with type 1 diabetes (search) and latent autoimmune diabetes in adults (search) (LADA).
In childhood-onset type 1 diabetes (search), vaccinated patients saw HbA1c drop from 7.84% to 7.30% over five years and spent up to 183% more time in a healthy blood sugar range.
In the LADA trial, BCG preserved or partially restored insulin production, while the placebo group required 22% more insulin over five years.
A tuberculosis vaccine first developed in the 1920s may offer a new therapeutic avenue for people with autoimmune forms of diabetes, according to results from two phase II clinical trials presented at the annual meeting of the American Diabetes Association in New Orleans on June 5–7.
The Bacillus Calmette-Guérin (BCG) vaccine, which contains a weakened version of Mycobacterium bovis, reduced insulin requirements and improved blood sugar control in both childhood-onset type 1 diabetes (search) and latent autoimmune diabetes in adults (search) (LADA), researchers led by Dr. Denise Faustman of Massachusetts General Hospital reported.
"The results exceeded my expectations," Faustman told Live Science.
Distinct Benefits Across Two Diabetes Populations
The trials tracked the effect of six BCG doses administered over five years in two separate patient groups.
In the first trial, 34 adults with childhood-onset type 1 diabetes (search) received the BCG vaccine while 24 received placebo. By five or more years post-vaccination, the BCG group demonstrated measurable improvements in blood sugar levels and reduced insulin use compared to placebo. Hemoglobin A1c (search) (HbA1c) in the vaccinated group fell from an average of 7.84% at baseline to 7.30% five years later — a drop of 0.54%, which exceeds the 0.5% threshold historically considered clinically meaningful for therapy approval. The vaccinated group also spent up to 183% more time in a healthy blood sugar range than at the start of the trial, without experiencing more episodes of dangerously low blood sugar than the unvaccinated group.
The second trial enrolled 95 adults with LADA, also known as "type 1.5" diabetes, an adult-onset autoimmune form distinct from type 2 diabetes. Of these, 68 received BCG and 27 received placebo. While the vaccine did not measurably lower blood sugar readings, it appeared to slow disease progression: vaccinated patients showed preserved — and in some cases, partially restored — insulin production over five years, as measured by C-peptide levels. Insulin use in the BCG group decreased by an average of nearly 3% over the trial period, whereas the placebo group required 22% more insulin at the five-year mark than at baseline.
Proposed Mechanisms
The researchers hypothesize two distinct mechanisms depending on the patient population. In LADA, blood samples from vaccinated participants carried lower levels of two key antibodies that drive the autoimmune attack on insulin-producing β-cells, suggesting BCG may protect remaining insulin-making cells from immune destruction.
In childhood-onset diabetes, where participants had little or no residual insulin production at baseline, Faustman and colleagues point to a mechanism they proposed in a 2018 study: BCG vaccinations shift regulatory T cells from a fat-burning state toward a sugar-burning state, enabling these immune cells to pull glucose from the blood while stopping once blood sugar normalizes, thereby preventing dangerous crashes.
"This opens your eyes to a whole new way to think about people with diabetes, and getting good blood-sugar control without a new device or new machine," Faustman said.
Cautious Reception and Next Steps
The findings have drawn both enthusiasm and skepticism. Dr. Gillian Goddard, a board-certified endocrinologist at NYU Langone Health who was not involved in the studies, noted that "the new data suggests that BCG could reduce insulin resistance and decrease the amount of insulin needed in patients with both late-onset and juvenile-onset type 1 diabetes (search)." She added that "these are phase 2 trials so further trials will be needed to fully understand the benefits of BCG in Type 1 diabetes, but it could be another tool in our arsenal for improving the lives of patients with type 1 diabetes."
Others urge caution. Dr. John Buse, an endocrinologist at the University of North Carolina School of Medicine, noted that the history of type 1 diabetes (search) research "is littered with losers and no blockbuster successes" and cautioned that improvements seen in these small trials may not hold up in a larger study. "It would take a big program to develop proof and that is probably the biggest barrier to finding out whether it is in fact useful," Buse said.
Åke Lernmark, a diabetes researcher at Lund University in Sweden, commented that "the importance of this study is that they demonstrate that, by activating the immune system with the vaccine, they are able to downregulate the autoimmunity." Immunologist Mihai Netea at Radboud University in Nijmegen, the Netherlands, added: "The data in LADA are very nicely in line with those old mouse studies. I find this very exciting and interesting."
Faustman's team has now studied over 350 adults, following individual participants for up to eight years, and another trial involving 250 children is currently underway. "This is the next step to prove this safe, affordable and durable drug can work on all stages of T1D," she said.
The only FDA-approved drug that delays insulin dependence is teplizumab, which is given early in the disease before patients need insulin. BCG, by contrast, may offer benefits even to patients who have already been on insulin for years, Goddard noted. Buse suggested that regardless of BCG's ultimate role, the "path of the future" lies in combination approaches that treat diabetes on multiple fronts simultaneously.