Effects of Stevia rebaudiana supplementation on glycemic, lipid, and liver markers in type 2 diabetic patients: a randomized controlled trial

Diabetes mellitus has become a global health issue, and antidiabetic drugs often cause adverse outcomes. Stevia rebaudiana is a natural sweetener with potential antihyperglycemic, antihyperlipidemic, and hepatoprotective effects. The study aimed to evaluate the 7-day and 60-day intervention effects of stevia leaf powder (SLP) capsules on glycemic control, lipid profile and liver enzymes in patients with type 2 diabetes mellitus (T2DM). A randomized controlled trial was conducted among 144 participants with T2DM (84 men and 60 women; 25–35 years). Participants were first assigned to a 7-day or a 60-day cohort ( n = 72 each) and then randomized 1:1 within each cohort, yielding four groups ( n = 36 each): 7-day study groups; control (T 0S ) and experimental (T 1S ) evaluated on day 0 and day 7, and 60-day study groups; control (T 0L ) and experimental (T 1L ) assessed on day 0, 30, and 60. The control groups received a balanced diet with conventional therapy, whereas the experimental groups received SLP capsule supplementation (1000 mg/day) in addition to a balanced diet with conventional therapy. Outcomes included fasting, postprandial glucose, glucose tolerance, glycated hemoglobin A1c (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), ​alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the 7-day cohort, fasting blood glucose at day 7 was lower in the SLP group than in the control group (between-group mean difference [MD] = 3.85 mg/dL; 95% CI: 2.57–5.13; t = 6.01; p < 0.001; Cohen’s d = 1.42), whereas no significant between-group differences were observed for the other parameters. In the 60-day cohort, significant Group × Time interactions indicated greater improvements in the SLP group than in the control group, most pronounced for fasting blood glucose (F = 323.80, p < 0.001, η² = 0.822), HbA1c (F = 124.11, p < 0.001, η² = 0.640), and glucose tolerance (F = 204.61, p < 0.001, η² = 0.745), followed by lipid and liver markers. Supplementation with SLP capsules (1000 mg/day), alongside conventional therapy, was associated with favorable changes in selected metabolic markers in the 60-day cohort. These preliminary findings suggest the potential of SLP as an adjunct to conventional T2DM management; however, the generalizability of the findings may be limited by the restricted age range, predominantly normal BMI profile, and single-centre recruitment. Furthermore, the absence of a placebo control, lack of quantitative dietary composition data, absence of quantitative steviol glycoside characterization, and lack of objective verification of adherence warrant cautious interpretation of the findings. The HbA1c results should also be interpreted cautiously given the 60-day intervention period. Larger, longer-duration randomized controlled trials are needed to confirm these preliminary findings. Clinical trial registered at URL: https://clinicaltrials.gov/study/NCT06645002 with trial number NCT06645002 on 16-10-2024. The pathways shown in this abstract represent proposed mechanisms based on previous literature and are provided for conceptual interpretation. TRPM5, AMPK, PPAR, and NF-κB pathways were not directly evaluated in the present study.