NEW YORK (Reuters Health) – Dapagliflozin can help children, adolescents and young adults with type 2 diabetes improve their hemoglobin A1c levels when added to other anti-diabetes therapies, according to a randomized controlled trial.
“Despite multiple agents across several drug classes available to adults with type 2 diabetes, treatment of young people with type 2 diabetes is complex and approved treatment options are considerably more limited,” Dr. William Tamborlane of Yale University School of Medicine, in New Haven, Connecticut, and colleagues say in The Lancet Diabetes & Endocrinology.
“The results of this phase 3 study show that oral treatment with dapagliflozin represents an additional treatment option for young people with type 2 diabetes,” they write.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin reduce the risk of heart and kidney disease in adults with type 2 diabetes, but these drugs are not approved in the U.S. for people younger than 18 years.
The study by Dr. Tamborlane and colleagues is the first placebo-controlled, randomized, phase-3 trial of dapagliflozin added to metformin, insulin or both in young people aged 10 to 24 years (mean age, 16.1 years) with type 2 diabetes and HbA1c between 6.5% and 11%.
Thirty-nine participants were randomly allocated to add dapagliflozin 10 mg once daily and 33 to matching placebo during a 24-week double-blind period, which was followed by a 28-week open-label safety extension in which all 72 participants received dapagliflozin.
The addition of dapagliflozin did not lead to a significant difference in HbA1c concentration versus placebo at 24 weeks in the intention-to-treat analysis (mean change in HbA1c, -0.25% vs. 0.50%; P=0.10).
However, a prespecified analysis of protocol-compliant participants showed a statistically significant decrease in HbA1c with add-on dapagliflozin versus placebo (mean change, -0.51% vs. 0.62%; P=0.012).
“The incongruent results between the intention-to-treat and compliance-based analyses are not unexpected, since young people have several barriers to medical adherence (including high rates of depression and poor motivation),” Dr. Kalie Tommerdahl of the University of Colorado School of Medicine, in Aurora, and colleagues point out in a comment published with the study.
Subgroup analyses suggested a benefit of dapagliflozin on HbA1c regardless of baseline characteristics such as race, HbA1c concentration, sex, and type of background therapy.
“In contrast with adult trials, no statistically significant effects were noted in this study for secondary endpoints, including changes in BMI or blood pressure. These differences might be ascribed, partly, to normal growth fluctuations related to puberty or the low baseline prevalence of hypertension in this trial,” the comment authors point out.
No new safety signals emerged, and there was a low risk of severe hypoglycemia and no episodes of diabetic ketoacidosis.
Dr. Tamborlane and colleagues say a unique aspect of this study was the inclusion of a subset of young adults aged 18 to 24 years, “an age range consistently under-represented in clinical trials of adults with type 2 diabetes.”
“With an increasing population of young people with type 2 diabetes, there is an unmet need for additional treatment options that are effective, well tolerated, and easy to administer. Therefore, our results suggest that dapagliflozin is the first oral glucose-lowering therapy since metformin to show a clinically relevant decrease in HbA1c concentration and acceptable safety in young people with type 2 diabetes,” the study team concludes.
“Considering the kidney protective effects of SGLT2 inhibition, a limitation of the trial by Tamborlane and colleagues was the absence of serial measures of albuminuria and estimated glomerular filtration rate (eGFR),” write Dr. Tommerdahl and co-authors.
“Ongoing SGLT2 inhibitor trials in young people with type 2 diabetes that include changes in albuminuria and eGFR as additional endpoints will help establish the efficacy of SGLT2 inhibitors in mitigating diabetic kidney disease risk in this population,” they add.
The study was funded by AstraZeneca. Several authors have disclosed financial relationships with the company.
SOURCE: https://bit.ly/3vns9WD and https://bit.ly/37SdRoK The Lancet Diabetes & Endocrinology, online April 1, 2022.
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