Efficacy and safety of the addition of sitagliptin to treatment of youth with type 2 diabetes and inadequate glycemic control on metformin without or with insulin.

Abstract

OBJECTIVE:

To assess the efficacy and safety of sitagliptin in youth with type 2 diabetes (T2D) inadequately controlled with metformin ± insulin.

STUDY DESIGN:

Data were pooled from two 54-week, double-blind, randomized, placebo-controlled studies of sitagliptin 100 mg daily or placebo added onto treatment of 10- to 17-year-old youth with T2D and inadequate glycemic control on metformin ± insulin. Participants (N = 220 randomized and treated) had HbA1c 6.5%-10% (7.0%-10% if on insulin), were overweight/obese at screening or diagnosis and negative for pancreatic autoantibodies. The primary endpoint was change from baseline in HbA1c at Week 20.

RESULTS:

Treatment groups were well balanced at baseline (mean HbA1c = 8.0%, BMI = 30.9 kg/m2 , age = 14.4 years [44.5% <15], 65.9% female). The dose of background metformin was >1500 mg/day for 71.8% of participants; 15.0% of participants were on insulin therapy. At Week 20, LS mean changes from baseline (95% CI) in HbA1c for sitagliptin/metformin and placebo/metformin were -0.58% (-0.94, -0.22) and -0.09% (-0.43, 0.26), respectively; difference = -0.49% (-0.90, -0.09), p = 0.018; at Week 54 the LS mean (95% CI) changes were 0.35% (-0.48, 1.19) and 0.73% (-0.08, 1.54), respectively. No meaningful differences between the adverse event profiles of the treatment groups emerged through Week 54.

CONCLUSIONS:

These results do not suggest that addition of sitagliptin to metformin provides durable improvement in glycemic control in youth with T2D. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01472367, NCT01760447; EudraCT: 2011-002529-23/2014-003583-20, 2012-004035-23).

• Authors: Muhammad Yazid Jalaludin, Asma Deeb, Philip Zeitler, Raymundo Garcia, Ron S Newfield, Yulia Samoilova, Carmen A Rosario, Naim Shehadeh, Chandan K Saha, Yilong Zhang, Martina Zilli, Lynn W Scherer, Raymond L H Lam, Gregory T Golm, Samuel S Engel, Keith D Kaufman, R Ravi Shankar
• Journal: Pediatric diabetes (Pediatr Diabetes) Vol. 23 Issue 2 Pg. 183-193 (03 2022) ISSN: 1399-5448 [Electronic] Denmark
• PMID: 34779103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Metformin
• Sitagliptin Phosphate

Topics

• Administration, Oral
• Adolescent
• Blood Glucose (analysis)
• Child
• Diabetes Mellitus, Type 2 (drug therapy, physiopathology)
• Double-Blind Method
• Drug Therapy, Combination (methods, statistics & numerical data)
• Female
• Glycated Hemoglobin (analysis)
• Humans
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Male
• Metformin (pharmacology, therapeutic use)
• Patient Safety (standards, statistics & numerical data)
• Sitagliptin Phosphate (pharmacology, therapeutic use)
• Treatment Outcome