SAT-LB025 Analysis of Benefit/Risk in the Subgroup of Patients with BMI of >=27 Kg/m(2) in the Dapagliflozin DEPICT-1 and -2 Trials in Type 1 Diabetes

Sodium glucose co-transporter-2 inhibitor (SGLT-2i) adjunct therapies have been studied in phase 3 programs for use in people with type 1 diabetes (T1D) and are currently under regulatory review for approval in adults in North America, Europe, and Japan. The DEPICT-1 and -2 programs assessed dapagliflozin (DAPA) 5 and 10 mg in adults with T1D. Treatment with DAPA in people with T1D resulted in important benefits with a manageable risk profile, though there was a higher incidence of events adjudicated as definite DKA in those receiving DAPA. During the 52-week study period, in the total population, the proportion of patients with events adjudicated as definite DKA events was 4.0% and 1.1% in the DAPA 5 mg and PBO groups, with incidence rates of 4.6 and 1.3 per 100 patient years, respectively. However, in the subgroup of patients with BMI ≥27 kg/m², the proportion of patients with events adjudicated as definite DKA was reduced to 1.8% and 1.0%, with incidence rates per 100 patient-years of 1.9 and 1.2 in the DAPA 5 mg and PBO groups, respectively. Efficacy endpoint results for the subgroup with BMI ≥27 kg/m(2) were similar to the overall population. After 24 weeks of treatment, HbA1c decreased from a baseline mean of 8.43 to 7.98% in the 5 mg group vs. 8.40 to 8.38% for PBO, with a PBO-corrected difference of –0.43% (95% CI –0.55, –0.31). Mean insulin dose decreased from 72.07 to 64.65 IU in the 5 mg group vs. 70.90 to 70.37 IU for PBO, with a PBO-corrected difference of –10.24 IU (95% CI –13.52, –6.84). Mean body weight decreased from 91.22 to 88.54 kg in the 5 mg group vs. 92.89 to 93.15 kg for PBO, with a PBO-corrected difference of –2.89 kg (95% CI –3.43, –2.36). As assessed by continuous glucose monitoring, mean interstitial glucose decreased from 192.52 to 176.19 mg/dL in the 5 mg group vs. 191.25 to 192.38 mg/dL for PBO, with a PBO-corrected difference of –16.81 mg/dL (95% CI –21.37, –12.25). Mean amplitude of glycemic excursions, a measure of glucose variability, decreased from 169.10 to 148.78 mg/dL in the 5 mg group vs. 164.94 to 163.71 mg/dL for PBO, with a PBO-corrected difference of –17.48 mg/dL (95% CI –22.28, –12.67). Mean time in the target glycemic range (glucose >70 and <180 mg/dL) increased from 44.17% to 53.65% in the 5 mg group vs. 44.67% to 44.44% for PBO, with a PBO-corrected difference of +9.69% (95% CI +7.61, +11.77) without increasing time in a hypoglycemic state (glucose <70 mg/dL). The proportion of patients achieving a reduction in HbA1c ≥0.5% without experiencing severe hypoglycemia was 47.2% in the 5 mg group vs. 21.3% for PBO, with 3.52 (95% CI 2.39, 5.21) greater odds of achieving this endpoint in those receiving 5 mg. In summary, while the benefit/risk profile of DAPA is favorable in the entire T1D study population, in this post-hoc analysis the benefit/risk appeared to be further enhanced in the subgroup of patients with BMI ≥27 kg/m² receiving DAPA 5 mg. Funded by AstraZeneca. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.