Clinical Overview: Oral Diabetes Medications in Children

The incidence of newly diagnosed type 2 diabetes in children continues to rise. The SEARCH for Diabetes in Youth study found that between 2002 and 2015, the rate of new cases of type 2 diabetes in children increased by 4.8% per year.¹

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Despite the surge in new cases, the treatment options in this population remain limited. To date, there are 3 oral medications that have been approved by the FDA: metformin (Glumetza, others), empagliflozin (Jardiance), and empagliflozin/metformin hydrochloride (Synjardy).

These medications are used along with diet and exercise to improve glycemic control in children 10 years of age and older with type 2 diabetes.²

Metformin

In December 2000, the FDA approved metformin as the first and only oral therapy for the treatment of type 2 diabetes in pediatric patients. Metformin is now considered first line treatment as monotherapy in children with metabolic stability, including HbA1c <8.5% and blood glucose levels <250 mg/dL, or as combination therapy with basal insulin in the presence of symptomatic hyperglycemia with an HbA1c >8.5% and blood glucose >250 mg/dL.³

The benefits of metformin in this population were shown in the Metformin in Obese Children and Adolescents (MOCA) trial, in which randomized participants received either metformin or placebo for 6 months.⁴ The study found that metformin was associated with a significant reduction in BMI from 37.1 (6.35) kg/m² at baseline to 36.56 (6.56) kg/m² at 3 months compared with placebo. Furthermore, researchers found a reduction in fasting glucose at 3 months from 4.83 (0.46) mmol/liter to 4.79 (0.46) mmol/liter in the metformin group compared with placebo.

Both reductions in body mass index and fasting glucose levels were sustained at 6 months.⁴ During the MOCA trial, metformin was well-tolerated, and no unexpected serious adverse event (AE) occurred other than the known AEs of metformin related to the gastrointestinal tract.⁴

The trial found that metformin is clinically useful and safe in tackling obesity and insulin resistance in children.

Jardiance and Synjardy

In June 2023, the SGLT2 inhibitors Jardiance and Synjardy were approved by the FDA to treat type 2 diabetes in children.² SGLT2 inhibitors are a novel class of antidiabetic drugs that reduce blood glucose levels by causing glucose to be excreted in the urine. Empagliflozin is the active ingredient in both Jardiance and Synjardy; however, Synjardy also contains metformin.

The efficacy and safety of empagliflozin in patients with type 2 diabetes who are 10 to 18 years of age were evaluated in the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO) trial.⁵

The trial found that the mean HbA1c change from baseline at week 26 was -0.84% in the empagliflozin group versus placebo.⁶ Patients treated with empagliflozin also had reductions in fasting plasma glucose.²

This confirmed that the use of empagliflozin resulted in clinically relevant reductions in HbA1c.⁶ AEs in the empagliflozin group were similar to those reported in adults, such as urinary tract infections and female fungal infections.²

The importance for pharmacists of the recent approvals of Jardiance and Synjardy in children 10 years of age and older

Pharmacists play a crucial role in providing appropriate counseling and education for children diagnosed with chronic conditions, such as type 2 diabetes. In 2016, a qualitative study was conducted to explore the perspectives of children regarding their perceptions on pharmacist-provided counseling.

The study showed that children were comfortable and receptive to pharmacists educating them about their medicines.⁷ In addition, researchers found that children relied on pharmacists to explain to them how medications affect the human body.⁷

Ultimately, pharmacists are the medication experts, making them well suited to educate children about their medicines.⁷

References

1. Rates of New Diagnosed Cases of Type 1 and Type 2 Diabetes Continue to Rise Among Children, Teens. Centers for Disease Control and Prevention. December 30, 2022. Accessed July 12, 2023. https://www.cdc.gov/diabetes/research/reports/children-diabetes-rates-rise.html.
2. FDA Approves New Class of Medicines to Treat Pediatric Type 2 Diabetes. FDA. News release. June 20, 2023. Accessed July 12, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-class-medicines-treat-pediatric-type-2-diabetes.
3. Alfaraidi H, Samaan MC. Metformin therapy in pediatric type 2 diabetes mellitus and its comorbidities: A review. Front Endocrinol (Lausanne). 2023; 13:1072879. Published Feb 6, 2023. Accessed July 12, 2023. doi:10.3389/fendo.2022.1072879.
4. D. Kendall and others, Metformin in Obese Children and Adolescents: The MOCA Trial, The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 1, January 1 2013, pages 322–329. Accessed July 12, 2023. https://doi.org/10.1210/jc.2012-2710.
5. Boehringer Ingelheim. Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO)TM. ClinicalTrials.gov. June 13, 2023. Accessed July 12, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03429543.
6. Laffel LM, Danne T, Klingensmith GJ, et al. Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial. Lancet Diabetes Endocrinol. 2023;11(3):169-181. Accessed July 12, 2023. doi:10.1016/S2213-8587(22)00387-4.
7. Abraham O, Brothers A, Alexander DS, Carpenter DM. Pediatric medication use experiences and patient counseling in community pharmacies: Perspectives of children and parents. Journal of the American Pharmacists Association. November 11, 2016. Accessed July 12, 2023. https://www.sciencedirect.com/science/article/pii/S1544319116308068.