Background Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. Current guidelines don’t recommend TB preventive therapy (TPT) for people with DM due to an absence of evidence.

Methods PROTID is the first randomized, double-blind trial to evaluate the efficacy and safety of 12 weekly doses of rifapentine/isoniazid (3HP) as TPT in people with DM who have latent tuberculosis infection (LTBI, n=3000), with a parallel cohort (n=1000) to measure TB risk in individuals with DM tested negative for LTBI. PROTID, run in Uganda and Tanzania, will also examine optimal ways of screening for active and latent TB, evaluate quality of DM and DM-TB care, establish cost-effectiveness and population impact, and archive samples for pathophysiological studies.

Results As of May 2023, 1890 participants have been screened, of whom 56.2% were LTBI-test positive, 8.5% HIV-infected, 0.5% diagnosed with TB disease and 4.9% reported previous TB. 740 participants (39.2%) have been enrolled in the trial, and 377 in the parallel cohort. Among those screened (mean age 55.8 years, 71.7% female), the mean duration of DM was 8.8 years; 38.2% were overweight and 32.2% obese, with 26.8% on insulin and a mean HbA1c of 9.4%. Further characterization showed hypertension (62.7%), myocardial infarction (1.0%), stroke (3.4%), foot amputations (5.0%), visual loss (60.9%), and peripheral neuropathy (76.9%).

Conclusion PROTID will provide essential evidence regarding prevention of DM-associated TB, and DM care in sub-Saharan Africa. Its initial results show a high burden of TB and LTBI and common HIV co-infection among people with DM in Tanzania and Uganda. DM is characterized by inadequate glycemic control and frequent complications, underlining the need for interventions to improve access and quality of DM care.