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Original ArticleFree Preview

Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes

List of authors.
  • Silva A. Arslanian, M.D.,
  • Tamara Hannon, M.D.,
  • Philip Zeitler, M.D., Ph.D.,
  • Lily C. Chao, M.D.,
  • Claudia Boucher-Berry, M.D.,
  • Margarita Barrientos-Pérez, M.D.,
  • Elise Bismuth, M.D.,
  • Sergio Dib, M.D., Ph.D.,
  • Jang Ik Cho, Ph.D.,
  • and David Cox, Ph.D.
  • for the AWARD-PEDS Investigators*

Abstract

Background

The incidence of type 2 diabetes mellitus is increasing among youths. Once-weekly treatment with dulaglutide, a glucagon-like peptide-1 receptor agonist, may have efficacy with regard to glycemic control in youths with type 2 diabetes.

Methods

Download a PDF of the Research Summary.

In a double-blind, placebo-controlled, 26-week trial, we randomly assigned participants (10 to <18 years of age; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.75 mg, or dulaglutide at a dose of 1.5 mg. Participants were then included in a 26-week open-label extension study in which those who had received placebo began receiving dulaglutide at a weekly dose of 0.75 mg. The primary end point was the change from baseline in the glycated hemoglobin level at 26 weeks. Secondary end points included a glycated hemoglobin level of less than 7.0% and changes from baseline in the fasting glucose concentration and BMI. Safety was also assessed.

Results

A total of 154 participants underwent randomization. At 26 weeks, the mean glycated hemoglobin level had increased in the placebo group (0.6 percentage points) and had decreased in the dulaglutide groups (–0.6 percentage points in the 0.75-mg group and −0.9 percentage points in the 1.5-mg group, P<0.001 for both comparisons vs. placebo). At 26 weeks, a higher percentage of participants in the pooled dulaglutide groups than in the placebo group had a glycated hemoglobin level of less than 7.0% (51% vs. 14%, P<0.001). The fasting glucose concentration increased in the placebo group (17.1 mg per deciliter) and decreased in the pooled dulaglutide groups (−18.9 mg per deciliter, P<0.001), and there were no between-group differences in the change in BMI. The incidence of gastrointestinal adverse events was higher with dulaglutide therapy than with placebo. The safety profile of dulaglutide was consistent with that reported in adults.

Conclusions

Treatment with dulaglutide at a once-weekly dose of 0.75 mg or 1.5 mg was superior to placebo in improving glycemic control through 26 weeks among youths with type 2 diabetes who were being treated with or without metformin or basal insulin, without an effect on BMI. (Funded by Eli Lilly; AWARD-PEDS ClinicalTrials.gov number, NCT02963766.)

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Funding and Disclosures

Presented in part at the 82nd Scientific Sessions of the American Diabetes Association (June 3–7, 2022).

Supported by Eli Lilly.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on June 4, 2022, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank Pam Anderson, M.D. (retired from Eli Lilly), for contributions to the original trial design; Rachel Gregory, M.B.A. (of Eli Lilly), for contributions to clinical trial management; the site personnel who assisted with the trial; Emily K. Blue, Ph.D., and Ciara O’Neill, Ph.D. (both of Eli Lilly), for medical writing and editing assistance with an earlier version of the manuscript; and all the participants and their families.

Author Affiliations

From the Center for Pediatric Research in Obesity and Metabolism, Division of Pediatric Endocrinology, Diabetes, and Metabolism, University of Pittsburgh, School of Medicine, UPMC Children’s Hospital of Pittsburgh, Pittsburgh (S.A.A.); the Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children (T.H.), and Eli Lilly (J.I.C., D.C.) — both in Indianapolis; Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora (P.Z.); Children’s Hospital Los Angeles, Los Angeles (L.C.C.); the Department of Pediatric Endocrinology, University of Illinois Medical Center at Chicago, Chicago (C.B.-B.); the Division of Pediatric Endocrinology, Hospital Ángeles Puebla, Puebla City, Mexico (M.B.-P.); the Department of Pediatric Endocrinology, Assistance Publique–Hôpitaux de Paris, Robert Debré Hospital, Paris (E.B.); and the Diabetes Center of Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo (S.D.).

Dr. Arslanian can be contacted at or at the Division of Pediatric Endocrinology, Diabetes, and Metabolism, University of Pittsburgh, School of Medicine, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave., FOB 6th Fl., Pittsburgh, PA 15224.

A list of the AWARD-PEDS Investigators is provided in the Supplementary Appendix, available at NEJM.org.

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