Contemporary Clinical Trials Communications · Nov 2026

Non-Sugar Sweetener Consumption and Glycemic Control in Middle-aged and Older Adults with Prediabetes: Background, Design, and Methods of a Controlled Feeding Trial

By Boone JT, Capra BT, Davy BM et al.

Type 2 diabetes (T2D) and prediabetes are rising globally and constitute a significant metabolic disease burden. Development of these conditions involves insulin resistance, declining β-cell function, chronic low-grade inflammation, and gut microbiome disruption. Middle-aged and older adults comprise over one-third of individuals with T2D and 50% of those with prediabetes. Non-sugar sweeteners (NSS) are widely promoted as a strategy to reduce added sugar intake and help manage blood glucose concentrations. Adults with or at risk for T2D are among the highest users of NSS. However, the impact of NSS on glucose homeostasis remains unclear due to heterogeneity across trials, including short duration, inconsistent dosing, predominantly healthy participants, and infrequent assessment of individual NSS, which limits the ability to establish clear intake recommendations. To address these gaps, two three-arm randomized controlled feeding trials were designed to test four NSS. Adults aged ≥40 years with prediabetes will follow a 6-week standardized eucaloric diet reflecting typical U.S. intake, which includes a 2-week lead-in diet followed by a 4-week intervention period. In Trial 1, participants will be randomized to one of two intervention groups (sucralose or aspartame) or a control group receiving no NSS. In Trial 2, participants will be randomized to one of two intervention groups (acesulfame potassium or saccharin) or a control group receiving no NSS. The intervention groups will receive the respective NSS at 25% of the FDA-established acceptable daily intake (ADI), adjusted for body weight (mg/kg). The primary outcome for both trials is 24-hour glycemic control and insulin sensitivity in response to intake of specific NSS types compared with an identical control condition. Secondary outcomes include markers of inflammation (e.g., TNF-α and MCP-1) and changes in gut microbiome composition.

doi.org/10.1016/j.conctc.2026.101707 Open access Interventions