Saxagliptin/dapagliflozin is non‐inferior to insulin glargine in terms of β‐cell function in subjects with latent autoimmune diabetes in adults: A 12‐month, randomized, comparator‐controlled pilot study

Aim: To compare the efficacy and safety of saxagliptin/dapagliflozin and insulin glargine in people with latent autoimmune diabetes in adults (LADA). Methods: In this phase 2b multicentre, open-label, comparator-controlled, parallel-group, non-inferiority study, we randomly assigned 33 people with LADA who had a fasting C-peptide concentration >= 0.2 nmol/L (0.6 ng/mL) to receive 1-year daily treatment with either the combination of saxagliptin (5 mg) plus dapagliflozin (10 mg) or insulin glargine (starting dose: 10 IU), both on top of metformin. The primary outcome was the 2-h mixed meal-stimulated C-peptide area under the curve (AUC), measured 12 months after randomization. Secondary outcomes were glycated haemoglobin (HbA1c) levels, change in body mass index (BMI), and hypoglycaemic events. Results: In the modified intention-to-treat analysis, the primary outcome was similar in participants assigned to saxagliptin/dapagliflozin or to insulin glargine (median C-peptide AUC: 152.0 ng*min/mL [95% confidence interval {CI} 68.2; 357.4] vs. 122.2 ng*min/mL [95% CI 84.3; 255.8]; p for noninferiority = 0.0087). Participants randomized to saxagliptin/dapagliflozin lost more weight than those randomized to insulin glargine (median BMI change at the end of the study: -0.4 kg/m(2) [95% CI -1.6; -0.3] vs. +0.4 kg/m(2) [95% CI -0.3; +1.1]; p = 0.0076). No differences in HbA1c or in the number of participants experiencing hypoglycaemic events were found. Conclusions: Saxagliptin/dapagliflozin was non-inferior to glargine in terms of beta-cell function in this 12-month, small, phase 2b study, enrolling people with LADA with still viable endogenous insulin production. Weight loss was greater with saxagliptin/dapagliflozin, with no differences in glycaemic control or hypoglycaemic risk.