A multi-center randomized controlled trial conducted across six teaching hospitals in Chile, Argentina, and Uruguay has produced results that the diabetes research community is describing as remarkable. The MATE-DM trial (Mate as Adjunctive Therapy in Early Diabetes Management) enrolled 720 adults with pre-diabetes or newly diagnosed Type 2 diabetes and demonstrated that standardized yerba mate extract supplementation, taken alongside standard dietary counseling, reduced glycated hemoglobin (HbA1c) levels by 0.8 percentage points over 24 weeks — an effect size comparable to metformin, the current first-line pharmaceutical treatment.
The trial, whose results were published in The New England Journal of Medicine in February 2026, represents the largest and most rigorously designed clinical study ever conducted on yerba mate's metabolic effects. Participants were randomized to receive either a standardized mate extract capsule containing 500 milligrams of total polyphenols (equivalent to approximately three cups of traditionally prepared mate) or an identical placebo capsule, taken three times daily with meals.
Primary and Secondary Outcomes
The primary endpoint — change in HbA1c from baseline to 24 weeks — showed a mean reduction of 0.81 percentage points in the mate group versus 0.23 points in the placebo group (p < 0.0001). For context, metformin typically produces HbA1c reductions of 0.5 to 1.5 percentage points depending on baseline severity. Notably, 38 percent of participants in the mate group achieved HbA1c values below the diabetic threshold of 6.5 percent by week 24, compared to 12 percent in the placebo group.
Secondary outcomes were equally encouraging. Fasting plasma glucose decreased by an average of 22 mg/dL in the mate group. HOMA-IR, a measure of insulin resistance, improved by 18 percent. Body weight decreased by a mean of 2.3 kilograms in the mate group versus 0.7 kilograms in the placebo group, suggesting that mate's effects on glycemic control may be partially mediated through improved body composition and energy metabolism.
These results suggest that yerba mate has the potential to serve as a first-line adjunctive therapy in the management of pre-diabetes and early Type 2 diabetes. The safety profile was excellent — no serious adverse events were attributed to the intervention — and the effect size was clinically meaningful by any standard.
Mechanism of Action
The research team identified two primary mechanisms underlying mate's glycemic effects. First, chlorogenic acid — the predominant polyphenol in Ilex paraguariensis — inhibits the enzyme glucose-6-phosphatase in the liver, reducing hepatic glucose output. This is the same pathway targeted by metformin, explaining the comparable effect sizes. Second, mate's saponin compounds were shown to enhance the expression of the GLUT-4 glucose transporter in skeletal muscle tissue, improving peripheral glucose uptake by approximately 24 percent — a mechanism distinct from metformin and potentially synergistic.
The MATE-DM trial has already catalyzed a Phase III confirmatory study, designed in accordance with FDA guidelines, that will enroll 2,400 participants across 20 sites in Latin America, Europe, and the United States. If the results are replicated, yerba mate extract could become the first plant-derived supplement to receive regulatory approval as an adjunctive diabetes medication — a milestone that would have profound implications for both the pharmaceutical industry and the yerba mate market.