Low-Carbohydrate Diet Compared with Canagliflozin for the Treatment of Diabetes-A Randomized Noninferiority Trial

Aims and Introduction: A low-carbohydrate diet (LCD) is effective for glycemic control in patients with diabetes. However, most previous studies have compared LCD with a low-fat or low-calorie diet. In this study, we used canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, as the positive control drug and aimed to establish the non-inferiority of LCD to canagliflozin in terms of blood glucose control. Methods: We conducted a 3-month, multicenter, randomized, open-label, parallel-controlled clinical trial involving patients with type 2 diabetes. Participants were randomly assigned in a 1:1 ratio to receive canagliflozin (100 mg/day) or LCD (carbohydrate intake < 20% of the total energy intake). The primary outcome was the change in HbA1c level, and the secondary outcomes were Continuous Glucose Monitoring (CGM)-measured time in the target glucose range of 3.9-10 mmol/L and the cost of antidiabetic agents. Results: In total, 121 participants from three hospitals were enrolled; 61 were administered canagliflozin and 60 were administered LCD. After the 3-month intervention, the mean change in HbA1c levels was -1.76% with canagliflozin and -2.23% with LCD (estimated difference, -0.47%; 95% confidence interval [CI], -0.85-0.08; P = 0.0180). Time in range (TIR) increased from 48.96% at baseline to 80.21% at 3 months in the canagliflozin group and from 52.08% to 93.75% in the LCD group. The TIR in the LCD group was significantly higher than that in the canagliflozin group (P = 0.0026). Additionally, in the LCD group, 10 of 52 patients who had been using antidiabetic drugs (19.2%) discontinued one oral antidiabetic drug or reduced their insulin doses. Conclusions: Our study showed that LCD was non-inferior to canagliflozin in glycemic control. Patients in the LCD group showed greater decline of HbA1c levels and higher TIR than those in the canagliflozin group. LCD reduced the cost of antidiabetic drugs. Disclosure Y. Gu: None. X. Xia: None. M. Xu: None. L. Li: None. J. Yin: None. Funding National Natural Science Foundation of China (82070885); Shanghai Municipal Education Commission (20172025); Xuhui Joint Research Projects on Important Diseases (XHLHGG202110)