The bacillus Calmette-Guérin (BCG) vaccine is one of the oldest vaccines in the world, developed for tuberculosis (TB) protection and for early stage bladder cancer therapy. BCG is an attenuated version of the virulent Mycobacterium bovis. BCG also shows promise as treatment for numerous inflammatory and autoimmune diseases. In patients with long-term type 1 diabetes, the TB vaccine BCG lowers blood sugar levels to near-normal after three years.

Follow-up of participants in clinical trials of a generic vaccine to reverse advanced type 1 diabetes finds significant clinical benefits, including restoration of near-normal blood sugar levels. Three years after receiving two administrations of the BCG vaccine four weeks apart, all members of a group of adults with longstanding type 1 diabetes showed an improvement in HbA1c to near normal levels – an improvement that persisted for the following five years.

On a randomized 8 years long prospective examination of type 1 diabetic subjects with long-term disease who received two doses of the BCG vaccine. After 3 years, BCG lowered hemoglobin A1c to near normal levels for the next 5 years. The BCG impact on blood sugars appeared to be driven by a novel systemic and blood sugar lowering mechanism in diabetes.

The study from the Massachusetts General Hospital (MGH) research team – reports that the effects of BCG vaccine on blood sugar control appear to depend on a totally novel metabolic mechanism that increases cellular consumption of glucose.

“This is clinical validation of the potential to stably lower blood sugars to near normal levels with a safe vaccine, even in patients with longstanding disease,” says Dr Denise Faustman, director of the MGH Immunobiology Laboratory, principal investigator of BCG clinical trials at MGH. “In addition to the clinical outcomes, we now have a clear understanding of the mechanisms through which limited BCG vaccine doses can make permanent, beneficial changes to the immune system and lower blood sugars in type 1 diabetes.”

Used for almost a century to prevent tuberculosis, BCG has been known for more than 30 years to boost production of a cytokine called tumor necrosis factor (TNF), which may be beneficial in autoimmune diseases both by eliminating the autoreactive T cells that attack an individual’s tissues – in the case of type 1 diabetes, pancreatic islets – and by inducing production of regulatory T cells (T-regs) that could prevent an autoimmune reaction. Dr Faustman’s team first reported in 2001 that inducing TNF production could cure type 1 diabetes in mice, but since TNF dosing is toxic in humans, clinical trials have utilised BCG for its ability to elevate TNF levels safely.

Initial clinical trial results two doses of BCG spaced four weeks apart led to reductions in autoreactive T cells, an increase in T-regs and what turned out to be a transient increase in insulin production. But by the end of that short, 20-week trial, there was no reduction in HbA1c, the established measure of blood sugar levels over time. An extension and expansion of that trial with long-term follow-up, the current results are based on data from 282 human study participants – 52 with type 1 diabetes who participated in the BCG clinical trials and 230 who contributed blood samples for mechanistic studies.

Regular monitoring of clinical trial participants found that HbA1c levels of those receiving BCG had dropped by more than 10 percent at three years after treatment and by more than 18 percent at four years. That reduction was maintained over the next four years, with treated participants having an average HbA1c of 6.65, close to the 6.5 considered the threshold for diabetes diagnosis, and with no reports of severe hypoglycemia. Participants in the placebo group and in a comparison group of patients receiving no treatment experienced consistent HbA1c elevations over the same eight-year time period.