Adjunctive glucose-lowering therapies may offer additional metabolic benefits for adults with type 1 diabetes mellitus (T1DM) who remain above glycemic targets despite insulin therapy. Findings presented at the ADA Scientific Sessions 2026 evaluated a sequential treatment strategy using semaglutide followed by dapagliflozin in overweight adults with T1DM.

The randomized study enrolled 78 adults with T1DM, body mass index (BMI) greater than 25 kg/m², and HbA1c between 7.5% and 11.0%. During the first 26 weeks, participants were randomized 2:1 to standard-of-care (SOC) insulin therapy with or without semaglutide, titrated to 1.0 mg weekly. During weeks 26 to 52, participants receiving semaglutide were further randomized to dapagliflozin 10 mg daily or placebo. The primary endpoint was change in HbA1c during the second treatment period.

Findings

• Semaglutide reduced HbA1c by 0.45% versus SOC during the first 26 weeks (95% CI, -0.78 to -0.13; P=0.0072).
• Body weight decreased by 10.2 kg with semaglutide compared with SOC (95% CI, -12.8 to -7.7; P<0.0001).
• During Period 2, dapagliflozin reduced HbA1c by an additional 0.46% versus placebo (95% CI, -0.78 to -0.14; P=0.003).
• No significant difference in body weight was observed between dapagliflozin and placebo during Period 2 (-1.0 kg; 95% CI, -2.72 to 0.66; P=0.2219).
• Over 52 weeks, participants assigned to semaglutide plus dapagliflozin achieved a greater reduction in HbA1c than those receiving SOC alone (difference, -0.36%; 95% CI, -0.67 to -0.05; P=0.0235).
• Level 2 hypoglycemia occurred more frequently with semaglutide than SOC during Period 1 (17 vs 9 events per patient-year; incidence rate ratio, 2.6; 95% CI, 1.4-5.0; P=0.0047), while one episode of ketoacidosis occurred in the placebo group during Period 2.

This study suggests that a sequential adjunctive strategy incorporating semaglutide and dapagliflozin may enhance metabolic management in overweight adults with T1DM receiving insulin therapy. The observed safety findings indicate that treatment intensification should be accompanied by careful monitoring and dose adjustment.