intranasal spray. The dosing and type of glucagon prescribed is age- and insurance- dependent. Evidence-Based Practice: Pediatric patients with newly diag- nosed type 2 diabetes are often initiated on insulin therapy. A recent study analyzed data from the Pediatric Diabetes Con- sortium, focusing on youth who were initiated on insulin then switched to intensive lifestyle intervention or metformin alone (Wolf et al., 2022). The primary endpoint was the time to treat- ment failure, which was defined as the need to restart insulin or metformin. A total of 183 participants with a mean age of 15 years were included in the analysis, and 54% of these pa- tients experienced treatment failure. In the subset of patients who were switched to intensive lifestyle intervention alone, 81% were restarted on insulin or metformin. Study authors identified that a higher hemoglobin A1C at study enrollment was a risk factor for treatment failure. These findings emphasize the im - portance of closely monitoring patients weaned off of insulin therapy, especially those with higher hemoglobin A1C values at diagnosis. The study also highlights the need for novel thera- pies to treat type 2 diabetes in children and adolescents. In addition to metformin and insulin, other medications have recently been approved for the treatment of T2DM in pediatric patients (ADA et al., 2022g). Liraglutide is a long-acting gluca- gon-like peptide-1 (GLP- 1) receptor agonist that works to lower blood glucose via several mechanisms (Lexicomp, 2022). Gluca- gon-like peptide-1 is an incretin hormone, which is secreted from the intestine upon ingestion of glucose. Analogs of GLP-1 increase glucose-dependent insulin secretion, decrease inappropriate glu- cagon secretion, increase pancreatic ß-cell growth, slow gastric emptying, and decrease food intake. Liraglutide is administered as a 0.6-mg once-daily subcutaneous injection and is increased weekly to achieve glycemic control, typically to a maximum daily dose of 1.8 mg. It is approved for use in children 10 years of age and older, similar to metformin. Also, like metformin, gastroin- testinal symptoms are the most common dose-limiting adverse effects, and these symptoms appear to decrease over time. Other notable adverse effects include acute kidney injury, which may be related to dehydration secondary to gastrointestinal symptoms, and hypersensitivity reactions, including angioedema and ana- Julia presents to her endocrinology office visit with a hemoglobin A1C that is above goal despite lifestyle changes and a pharmaco- logic regimen of metformin with insulin. What options does she have to improve her glycemic control? Discussion All patients should be encouraged to continue making lifestyle changes to promote a healthy weight. While Julia seems to have made significant improvements, she should ensure she is incor - porating moderate-intensity exercises of adequate duration each day of the week, including aerobic and strengthening activities. In addition, her nutrition should be reviewed to ensure the family home cooking incorporates a balanced, appropriately portioned diet with fruits and vegetables. While these lifestyle changes will be beneficial for weight loss and diabetes management, she will Monitoring Blood glucose monitoring depends on the patient’s pharmaco- therapy and subsequent risk of hypoglycemia (ADA et al., 2022g). At a minimum, glycemic status, typically via HbA1C, should be measured and assessed every three months. Values above the HbA1C goal may indicate nonadherence or the need for more intensive therapy. Many patients with T2DM require closer moni- toring of blood glucose levels, secondary to insulin treatment or acute illness. Rather than every-3-month HbA1C, blood glucose can be measured on a daily or hourly basis with blood glucose meters. Case study: Julia Question
phylaxis. In animal studies, thyroid C-cell tumors were noted, but these findings are undetermined in humans. Due to this potential risk, patients with a personal or family history of medullary thy- roid carcinoma or multiple endocrine neoplasia syndrome type 2 should avoid GLP-1 therapy. Other reported adverse reactions include gallbladder disease and pancreatitis, but these are not fully understood and the frequency in pediatric patients is not characterized. In clinical trials, patients receiving liraglutide along with basal insulin therapy were able to reduce their insulin doses by approximately 20% after titration to goal. Exenatide, another analog of the hormone incretin, is available in an extended-release formulation (Lexicomp, 2022). It is admin- istered as a 2-mg dose subcutaneously on a weekly basis. This medication was recently approved in children 10 years of age and older. Common adverse effects are mainly gastrointestinal or lo- calized at the injection site. A warning regarding risk of thyroid carcinomas exists, as this is a noted class effect in animal studies. Other adult-approved GLP-1 receptor agonists are undergoing study in pediatrics, but approval is pending. Evidence-Based Practice: In an international randomized study of patients age 10 to <18 years with type 2 diabetes, patients on standard of care therapy were given once weekly exenati- de or placebo (Tamborlane, Bishai, et al., 2022). Standard of care therapy included nutrition therapy and exercise alone or in combination with metformin and/or insulin for at least 2 months prior to enrollment. After 24 weeks of therapy, the mean be- tween-group difference in hemoglobin A1C was 0.85%, in favor of exenatide. Although there was a relatively small sample size, the findings support improved glycemic control when exenati - de was utilized as add-on therapy. Patients receiving metformin and/or GLP-1 receptor agonist ther- apy who are also receiving basal insulin may need therapy modi- fications. For those who are meeting targets for glycemic control, insulin can be tapered by 10%–30% every few days over several weeks (ADA et al., 2022g). For those who are not meeting their goals, multiple daily injections with rapid-acting insulin may need to be added. This may include prandial bolus doses or use of an insulin pump, similar to management of T1DM. also require intensification of her pharmacologic therapy to de - crease her hemoglobin A1C. The highest recommended daily dose of metformin is 2,000 mg, so this therapy is maximized. Her insulin can be titrated to effect with either an increase in her bas- al dose or the addition of intermittent bolus doses. While effec- tive, multiple daily doses of insulin can be burdensome and may place the patient at increased risk of hypoglycemia. Alternatively, a glucagon-like peptide-1 receptor agonist can be added to her therapy. Since she requires an approximate 1.3% reduction in her hemoglobin A1C, glycemic control may be possible without addi- tional insulin. Approved options for her age are either once-daily liraglutide or once-weekly exenatide. If started on one of these two medications, her blood glucose should be closely monitored in the event that she requires a basal insulin reduction over the weeks following initiation. Traditional methods of glucose monitoring require a lancing de- vice, lancets, test strips, and a blood glucose meter (ADA et al., 2022f). Meters and test strips must be compatible for use, which often depends on the brand name, and test strips should be rou- tinely checked for expiration. Specific instructions vary per manu - facturer, but generally steps are similar across product types. First, the patient should wash their hands and dry them well. This limits interference with the reading and increases accuracy of the result. Alternatively, an alcohol pad can be used to wipe the finger clean. Once the user’s hands are clean, they can insert a test strip into the port of the blood glucose meter in preparation for the blood
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