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Adjunct-to-insulin therapy using SGLT2 inhibitors in youth with type 1 diabetes: a randomized controlled trial

Farid H Mahmud1, Petter Bjornstad2,3,4, Cheril Clarson5

  • 1Hospital for Sick Children, Hospital for Sick Children Research Institute and University of Toronto, Toronto, Ontario, Canada. farid.mahmud@sickkids.ca.

Nature Medicine
|June 6, 2025
PubMed

Insights

Dapagliflozin, an SGLT2 inhibitor, reduced kidney filtration and improved glycemic control in adolescents with type 1 diabetes. This study found dapagliflozin safe and effective as an adjunct to insulin therapy.

Area of Science:

  • Nephrology
  • Endocrinology
  • Clinical Trials

Background:

  • Sodium glucose co-transporter 2 inhibitors (SGLT2i) are known to slow chronic kidney disease (CKD) progression in type 2 diabetes.
  • The efficacy and safety of SGLT2i in type 1 diabetes (T1D) require further investigation, particularly concerning kidney function and glycemic control in adolescents.

Purpose of the Study:

  • To evaluate the effect of dapagliflozin as an adjunct to insulin therapy on measured glomerular filtration rate (mGFR) in adolescents with T1D.
  • To assess the impact of dapagliflozin on glycemic control, body weight, and safety outcomes, including diabetic ketoacidosis (DKA), in this population.

Main Methods:

  • A 22-week, double-blind, randomized, placebo-controlled trial (ATTEMPT) involving 98 adolescents (12-21 years) with T1D.
  • Participants received either dapagliflozin 5 mg or placebo, alongside standard insulin therapy, with mandatory ketone monitoring and DKA risk education.
  • Primary outcome was the change in mGFR assessed by iohexol clearance.

Main Results:

  • Dapagliflozin significantly reduced mGFR by 8.8 ml/min/1.73 m² compared to placebo (P < 0.0001).
  • Greater mGFR reduction was observed in participants with higher baseline mGFR (r = -0.58, P < 0.0001).
  • Improvements were noted in HbA1c (decreased by 0.47%), time in range (increased by 9.0%), and body weight (decreased by 2.8 kg) with dapagliflozin. No significant difference in insulin dose was observed. Adverse events were similar, with one mild DKA case in the dapagliflozin group.

Conclusions:

  • Dapagliflozin, when used as an adjunct to insulin in youth with T1D, effectively reduces mGFR and improves glycemic control.
  • The treatment demonstrated a favorable safety profile when combined with diligent ketone monitoring and DKA risk mitigation strategies.

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