Comparative efficacy and safety of glucose-lowering drugs in children and adolescents with type 2 diabetes: A systematic review and network meta-analysis

Wu, Sijia; He, Yangkun; Wu, Yongbo; Ji, Yiman; Hou, Lei; Liu, Xinhui; Ge, Yilei; Yu, Yuanyuan; Yu, Yifan; Wang, Yun; Qian, Fengtong; Luo, Qingxin; Feng, Yue; Feng, Yuanjing; Wang, Danny J.J.; Huo, Meiling; Li, Hongkai; Xue, Fuzhong

doi:10.3389/fendo.2022.897776

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…Although DPP-4is are not approved for use in the pediatric population, a recent study conducted in youths (aged 10-17 years) with type 2 diabetes found that sitagliptin was generally well tolerated and had a safety profile similar to that reported in adults (48). Safety of DPP-4is for the treatment of type 2 diabetes in children and adolescents was also confirmed in a recent meta-analysis (49).…”

Section: Discussionmentioning

confidence: 81%

Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

Pinheiro,

Arruda

et al. 2023

Archives of Endocrinology and Metabolism

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Objective:The occurrence of partial remission (honeymoon phase) in type 1 diabetes (T1D) has been associated with a reduced risk of chronic microvascular complications of diabetes. We have published case reports showing that a combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3 (VIDPP-4i) can prolong the honeymoon phase in patients with new-onset T1D. In the present case-control study, we investigated the frequency of occurrence of clinical remission (CR) in patients with new-onset T1D after VIDPP-4i treatment. Subjects and methods: In this case-control study, we collected data spanning 10 years from medical records of 46 patients (23 females) recently diagnosed with T1D. Overall, 27 participants with CR (insulin dose-adjusted glycated hemoglobin [IDAA1c] ≤ 9) at 12 or 24 months composed the case group, and 19 participants without CR served as the control group. Chi-square with Yates correction was used to analyze the association between VIDPP-4i use and CR, and odds ratio (OR) was used to determine the chance of CR due to VIDPP-4i treatment exposure. Results: In all, 37 patients (80.4%) experienced CR at some time over 24 months. The mean CR duration was 13.15 ± 9.91 months. Treatment with VIDPP-4i was significantly associated with CR. At 24 months, the OR of CR after VIDPP-4i exposure was 9.0 (95% confidence interval [CI] 2.21-30.18, p = 0.0036). Additionally, 9 (33.6%) and 4 (14.8%) patients in the VIDPP-4i group experienced insulin-free CR at 12 and 24 months, respectively. Conclusion: Therapy with VIDPP-4i was associated with a higher frequency and duration of the honeymoon phase. Randomized controlled trials are needed to confirm these findings.

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Section: Discussionmentioning

confidence: 81%

Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

Pinheiro,

Arruda

et al. 2023

Archives of Endocrinology and Metabolism

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“…An exponential increase in the prevalence of obesity among adults and kids following the coronavirus disease 2019 (COVID 19) pandemic has contributed to the increased prevalence of T2DM in children. A network meta-analysis published in 2022 highlighted that metformin, saxagliptin, linagliptin, exenatide, liraglutide and dapagliflozin have been evaluated in different clinical trials in children with T2DM and advocated for the use of the saxagliptin metformin combination to treat T2DM in children [ 27 ]. Saxagliptin use has decreased significantly in adults with T2DM following the issue of a black box warning for heart failure [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…A network meta-analysis published in 2022 highlighted that metformin, saxagliptin, linagliptin, exenatide, liraglutide and dapagliflozin have been evaluated in different clinical trials in children with T2DM and advocated for the use of the saxagliptin metformin combination to treat T2DM in children. 27) Saxagliptin use has decreased significantly in adults with T2DM following the issue of a black box warning for heart failure. 28) Since then, many more studies have been published on oral antidiabetes medication use in children, especially SGLT2i like empagliflozin.…”

Section: Discussionmentioning

confidence: 99%

Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in children and young adults: a systematic review and meta-analysis

Nagendra,

Dutta,

Girijashankar

et al. 2024

Ann Pediatr Endocrinol Metab

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Purpose: Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap.Methods: Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events.Results: From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93–3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08–2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01–8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44–12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21–96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24–26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, β-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05–0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001).Conclusion: SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.

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“…An evaluation of the efficacy and safety of several glucose-lowering medications provides additional options for YODM management. Compared to FDA-approved drugs, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy, indicating the top ten treatment methods for YODM in individuals aged 10–17: saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide-2 mcg, sitagliptin+metformin, linagliptin-5 mg, linagliptin-1 mg, metformin, and exenatide-5/10 mcg ( 149 ).…”

Section: Comprehensive Management Strategies For Yodm From the Perspe...mentioning

confidence: 99%

Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance

Jia,

Zhang,

Zhang

et al. 2024

Front. Endocrinol.

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With changes in lifestyle behaviors, including dietary structure and habits, the prevalence of Youth-onset Type 2 Diabetes Mellitus (YODM) has increased 2 to 3 times compared to 30 years ago. YODM patients experience complications earlier, progress faster, and exhibit more severe symptoms. However, limited and inconclusive direct evidence, coupled with poor patient compliance, poses challenges in the clinical management of YODM. Apart from the continuous decline in pancreatic β-cell function and quantity, tissue-specific insulin resistance (IR) is also a typical characteristic of YODM. The main mechanisms of IR in YODM involve different aspects such as obesity, dietary imbalance, abnormal substance metabolism, chronic inflammation, oxidative stress, and hormonal fluctuations during adolescence. For the comprehensive management of YODM, besides achieving good control of blood glucose levels, it may be necessary to apply the most appropriate methods considering the uniqueness of the patient population and the specifics of the disease. Early identification and detection of the disease are crucial. Precise screening of patients with well-functioning pancreatic insulin β-cells, primarily characterized by IR and obesity, represents the population most likely to achieve diabetes remission or reversal through lifestyle modifications, medications, or even surgical interventions. Additionally, considering potential emotional disorders or the impact of adolescent hormones in these patients, health education for patients and caregivers is essential to make them aware of the long-term benefits of well-controlled blood glucose. In conclusion, adopting comprehensive management measures to achieve diabetes remission or reversal is the ideal goal. Controlling high blood glucose, obesity, and other risk factors related to diabetes complications is the next priority to delay the occurrence and progression of complications. A comprehensive perspective on IR provides insights and references for identifying YODM and its management strategies.

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Comparative efficacy and safety of glucose-lowering drugs in children and adolescents with type 2 diabetes: A systematic review and network meta-analysis

Cited by 7 publications

References 39 publications

Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in children and young adults: a systematic review and meta-analysis

Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance

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