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
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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: , 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).
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Affected young people have a more rapid deterioration in blood glucose levels, an attenuated response to diabetes medication, and more rapid development of diabetes complications.
“Affected young people have a more rapid deterioration in blood glucose levels, an attenuated response to diabetes medication, and more rapid development of diabetes complications (269 -273).”
From Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2022) · cites this paper as [273]
The Discussion (section 4; page not provided) describes a less durable response to metformin in youth, a greater decline in β-cell function than in adults, and differences in responses to antihyperglycemic medication. The Introduction (section 1; page not provided) notes an increased risk of early-onset complications, but does not establish that complications develop more rapidly. The claim also generalizes the medication response beyond the treatments discussed. (LLM, conf=0.84)
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Research works printed but not linked: 4
- Philip Zeitler is Editor-in-Chief of Pediatric Diabetes and did not participate in the review or editorial decisions related to this manuscript.
- Asma Deeb, Raymundo Garcia, Yulia Samoilova, Carmen A. Rosario, and Naim Shehadeh report no disclosures. AUTHOR CONTRIBUTIONS Muhammad Yazid Jalaludin, Asma Deeb, Philip Zeitler, Raymundo Garcia, Ron S. Newfield, Yulia Samoilova, Naim Shehadeh, Chandan K. Saha, Yilong Zhang, Carmen A. Rosario, Martina Zilli, Lynn W. Scherer, Raymond L. H. Lam, Gregory T. Golm, Samuel S. Engel, Keith D. Kaufman, and R. Ravi Shankar are responsible for the work described in this paper. Philip Zeitler, Yulia Samoilova, Chandan K. Saha, Yilong Zhang, Lynn W. Scherer, Gregory T. Golm, Samuel S. Engel, and Keith D. Kaufman conceived, designed, and/or planned the study. Muhammad Yazid Jalaludin, Asma Deeb, Philip Zeitler, Raymundo Garcia, Carmen A. Rosario, Martina Zilli, and Lynn W. Scherer acquired the data. Philip Zeitler, Yilong Zhang, and Raymond L. H. Lam analyzed the data. Muhammad Yazid Jalaludin, Asma Deeb, Philip Zeitler, Ron S. Newfield, Naim Shehadeh, Chandan K. Saha, Yilong Zhang, Martina Zilli, Gregory T. Golm, Samuel S. Engel, Keith D. Kaufman, and R. Ravi Shankar interpreted the results. Keith D. Kaufman drafted the manuscript. 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, and R. Ravi Shankar critically reviewed and/or revised the manuscript for important intellectual content. 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, and R. Ravi Shankar provided final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investi- gated and resolved. ETHICS STATEMENT Both studies (Sitagliptin Protocol 170, Clinical Trials.gov: NCT01472367, EudraCT: 2011-002529-23/2014-003583-20 and Sitagliptin Protocol 289, Clinical Trials.gov: NCT 01760447, EudraCT: 2012-004035-23) were conducted in accordance with principles of Good Clinical Practice and were approved by the appropriate institutional review boards and regula- tory agencies. Written informed consent was provided by the participant's parent or legal guardian, and assent was provided by the participant.
- Liang KY, Zeger SL. Longitudinal data analysis of continuous and dis- crete responses for pre-post designs. Indian J Stat. 2000;62: 134-148.
- The RISE Consortium. Effects of treatment of impaired glucose toler- ance or recently diagnosed type 2 diabetes with metformin alone or in combination with insulin Glargine on beta-cell function: compari- son of responses in youth and adults. Diabetes. 2019;68:1670-1680.
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- Authors
- Jalaludin, M. Y., Deeb, A., Zeitler, P., Garcia, R., Newfield, R. S., Samoilova, Y., Rosario, C. A., Shehadeh, N., Saha, C. K., Zhang, Y., Zilli, M., Scherer, L. W., Lam, R. L. H., Golm, G. T., Engel, S. S., Kaufman, K. D., & Shankar, R. R.
- Affiliations
- University of Malaya (MY)
- Sheikh Shakhbout Medical City (AE)
- Children's Hospital Colorado (US)
- Department of Internal Medicine and Clinical Endocrinology Centro de Estudios Clínicos y Especialidades Medicas (CECEM) Nuevo Leon Mexico
- University of California San Diego (US)
- Department of Pediatric Endocrinology and Diabetology Siberian State Medical University Tomsk Russia
- Department of Pediatric Endocrinology Hospital General Plaza de la Salud Santo Domingo Dominican Republic
- Rambam Health Care Campus (IL)
- Indiana University Indianapolis (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Shankar, R. Ravi
- ORCID
- Venue
- Pediatric Diabetes
- Publisher
- Wiley
- Published
- 2021-12-20
- Volume
- 23
- Issue
- 2
- Pages
- 183-193
- ISSN
- 1399-543X (ISSN-L)
- 1399-5448
- OpenAlex
- W3212080993
- Cited by
- 31
- References
- 42
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 10 · 2022: 4
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Pediatric Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Merck KGaA
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- sitagliptin, type 2 diabetes in youth, adolescents, glycemic control, HbA1c, metformin, insulin therapy, DPP-4 inhibitors, drug safety, treatment efficacy, overweight and obesity, adverse events, adjunctive therapy
- MeSH terms
- Sitagliptin Phosphate, Administration, Oral, Adolescent, Blood Glucose, Child, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Metformin, Treatment Outcome, Patient Safety
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