天美传媒

Empagliflozin; Type 1 diabetes; Sglt2 inhibitor; Adjunct therapy; Insulin dose reduction; Diabetic ketoacidosis; Glycemic control; HbA1c; Weight loss; Multi-center trial

Introduction

Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β-cells, necessitating lifelong insulin therapy. Despite advances in insulin delivery systems and continuous glucose monitoring, many patients struggle to achieve optimal glycemic control without experiencing hypoglycemia or weight gain [1-5]. Adjunct therapies to insulin are increasingly explored to enhance glycemic outcomes and address metabolic comorbidities. Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor approved for Type 2 diabetes, has shown promise in improving glycemic control and reducing body weight by promoting urinary glucose excretion. However, its use in T1DM remains controversial due to the associated risk of diabetic ketoacidosis (DKA). This multi-center trial evaluates the safety and efficacy of empagliflozin as adjunct therapy to insulin in adults with T1DM [6-10].

Discussion

In this randomized, double-blind, placebo-controlled trial conducted across 12 diabetes care centers, 410 adults with T1DM were enrolled and assigned to receive either empagliflozin (10 mg/day or 25 mg/day) or placebo, in addition to their existing insulin regimen, for a duration of 26 weeks. Participants were aged 18–65 years, with a baseline HbA1c between 7.5% and 10%, and BMI > 22 kg/m². The primary endpoint was change in HbA1c from baseline. Secondary endpoints included changes in total daily insulin dose, body weight, time in range (CGM data), and incidence of adverse events, particularly DKA.

Empagliflozin use led to statistically significant reductions in HbA1c compared to placebo: −0.47% in the 10 mg group and −0.58% in the 25 mg group versus −0.12% in placebo. Time in range (70–180 mg/dL) improved by 10–14% in the treatment arms, and total daily insulin dose was reduced by an average of 14%. Additionally, participants experienced modest but clinically relevant weight loss (mean: −2.5 to −3.8 kg) in both empagliflozin groups.

However, the rate of confirmed or possible DKA was higher in the empagliflozin groups, especially among individuals with insulin reduction >20% or those using insulin pumps. Six DKA events occurred in the empagliflozin arms versus one in the placebo group. Other adverse events included increased frequency of urinary tract infections and genital mycotic infections, which were mostly mild to moderate in severity. Patients were educated throughout the study on ketone monitoring and hydration strategies to minimize DKA risk.

Subgroup analyses indicated that patients with higher baseline HbA1c or elevated BMI experienced the greatest benefit in glycemic control and weight reduction. Clinicians involved in the trial emphasized the need for strict patient selection, close ketone monitoring, and clear education on insulin dose adjustments when using empagliflozin in T1DM.

Conclusion

Empagliflozin as an adjunct therapy in adults with Type 1 diabetes significantly improves glycemic control, reduces insulin requirements, and promotes weight loss. However, the benefits are tempered by an increased risk of diabetic ketoacidosis, highlighting the importance of careful patient monitoring and education. While the findings support the therapeutic potential of SGLT2 inhibitors in T1DM, their use should be reserved for well-informed and closely supervised individuals. Future research should focus on refining dosing strategies, risk mitigation protocols, and long-term outcomes to determine the safest and most effective integration of empagliflozin into Type 1 diabetes care.

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