Objective: To study the efficacy and safety of metreleptin therapy in patients with suboptimally controlled type 1 diabetes mellitus (T1DM).

Research design and methods: After a baseline period of 4 weeks, five female and three male patients with T1DM (mean age 33 years, BMI 23.8 kg/m²) received metreleptin (0.08 mg/kg/day in females and 0.04 mg/kg/day in males) subcutaneously twice daily for 20 weeks followed by an off-therapy period of 4 weeks.

Results: Metreleptin therapy did not lower HbA_1c significantly compared with the baseline value (mean difference -0.19% [-2.0 mmol/mol] and -0.04% [-0.5 mmol/mol] at 12 and 20 weeks, respectively). Mean body weight reduced significantly by 2.6 and 4.7 kg (P = 0.003) and daily insulin dose by 12.6% and 15.0% at week 12 and 20 (P = 0.006), respectively.

Conclusions: Metreleptin is safe but may not be efficacious in improving glycemic control in patients with T1DM, although it reduces body weight and daily insulin dose modestly.