Comparison of a Ketogenic Diet Program to the ADA Standards of Care in Patients Living with Diabetes: A Randomised Crossover Trial

Background : Ketogenic diets have shown promise for glycaemic control, but studies on the added benefits of strict carbohydrate intake reduction among rigorously controlled patients remain limited. Methods : We conducted a pre-registered, open-label, randomised crossover trial comparing a ketogenic meal program (Glyvance™, <50 g carbohydrates/day) to meals based on the American Diabetes Association (ADA) recommendations (~190 g carbohydrates/day). The protocol consisted of a 2-day baseline, two 5-day dietary intervention periods, and a 2-day washout between periods. The primary outcome was daily mean glucose measured via continuous glucose monitoring. Secondary outcomes included time in range (70-180 mg/dL) and satiety. Data were analysed using linear mixed-effects models in both intention-to-treat and per-protocol analyses. All meals for both arms were provided, and adherence was defined as > 80% of the meals without any additional foods from what was provided. Results : In the intention-to-treat analysis (n=17), Glyvance™ significantly reduced daily mean glucose by 20 mg/dL compared to baseline (p<0.001). Contrastingly, the ADA diet did not show a significant effect. For patients with Pre-Diabetes and Type 2 Diabetes (n=11), Glyvance™ reduced glucose by 23 mg/dL (p<0.001) and the ADA diet by 9 mg/dL (p=0.01). In the per-protocol analysis, for patients with Pre-Diabetes and Type 2 Diabetes, both diets improved time in range, ^Glyvance™ (4.3%, p<0.001) and the ADA diet (2.4%, p=0.008). No diet-sequence effects were observed in any of the analyses. Conclusions : ^Glyvance™ , a door-delivered ketogenic meal program, achieved superior glycaemic outcomes compared to ADA-based meals in well-controlled patients living with diabetes and pre-diabetes. These findings support further research on its potential as an effective intervention for diabetes management.