Lifestyle interventions remain the treatment of choice in pediatric obesity, but concomitant pharmacotherapy may be beneficial in some patients. Orlistat should be considered as second-line therapy for pediatric obesity. Evidence suggests that other diabetes and antiepileptic medications may also provide weight-loss benefits, but safety should be further evaluated.
Demonstrated secondary benefits in addition to efficacy may make GLP-1 agonists and DPP-4 inhibitors a more favorable option than other second-line T2DM therapies.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in combination with insulin to manage type 2 diabetes mellitus, and four agents are currently approved for this indication: exenatide, liraglutide, dulaglutide, and albiglutide. The distinctive properties of GLP-1 RAs-potential hemoglobin A1c (A1C) reduction, weight loss, potential to reduce insulin doses, and lower hypoglycemia risk-have made these agents potential treatment options for patients with type 1 diabetes mellitus (T1DM) as well. These positive effects are due to glucose-dependent insulin secretion, reduced glucagon secretion, increased satiety, and delayed gastric emptying. Patients with T1DM are unable to suppress glucagon during meals, which contributes to postprandial hyperglycemia and may be improved with GLP-1 therapy. In this review, we evaluated the available literature on the clinical efficacy and safety of GLP-1 RAs in patients with T1DM. We conducted a search of the PubMed (1966-May 2016) and Ovid (1946-May 2016) databases. Abstracts presented at the scientific and clinical sessions of the American Diabetes Association and the American Association of Clinical Endocrinologists were also searched. The references of the published articles were also reviewed to identify additional studies appropriate for inclusion. All identified articles published in English were evaluated. Studies were included if they evaluated the clinical use or safety of GLP-1 RAs in patients with T1DM. Twelve studies were included, with four evaluating exenatide, one evaluating exenatide extended release, and seven evaluating liraglutide. Both exenatide and liraglutide showed significant reductions in hemoglobin A1C, plasma glucose concentration, body weight, and insulin doses when administered to patients with T1DM already receiving insulin therapy, without increasing the occurrence of hypoglycemia. Adverse effects were mostly gastrointestinal in nature but were mild and transient. Patients who may benefit most are those experiencing adverse effects from insulin, those not at their A1C goal but hypoglycemia prevents insulin titration, and those who may benefit from weight loss.
Type 1 diabetes mellitus (T1DM) is characterized by relative or absolute insulin deficiency. Despite treatment with insulin therapy, glycemic goals are not always met, and insulin therapy is sometimes limited by adverse effects, including hypoglycemia and weight gain. Several adjunctive therapies have been evaluated in combination with insulin in patients with T1DM to improve glycemic control while minimizing adverse effects. Pramlintide, an amylin analog, can improve glycemic control, primarily through lowering postprandial blood glucose levels. Patients may experience weight loss and an increased risk of hypoglycemia and require additional mealtime injections. Metformin provides an inexpensive, oral treatment option and may reduce blood glucose, especially in overweight or obese patients with minimal risk of hypoglycemia. Metformin may be more effective in patients with impaired insulin sensitivity. Glucagon-like peptide-1 receptor agonists reduce primarily postprandial blood glucose and insulin dose and promote weight loss. They are expensive, cause transient nausea, may increase risk of hypoglycemia and require additional injections. Sodium–glucose transport-2 inhibitors improve glycemic control, promote weight loss and have low risk of hypoglycemia with appropriate insulin adjustment; however, these agents may increase the risk of diabetic ketoacidosis in patients with T1DM. Patient-specific characteristics should be considered when selecting adjunctive therapy for patients with T1DM. Close monitoring, insulin dose adjustments and patient education are all important to ensure safe and effective use of these agents.
Lixisenatide provides an additional GLP-1RA option, which may have more postprandial blood glucose-lowering effects than the other agents in the class because of its shorter half-life and effects on delaying gastric emptying.
Data Sources: A PubMed (1966 to October 2018) search was conducted using the following keywords: nebivolol, valsartan, and hypertension (HTN). Additional sources were identified by references. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacology, pharmacokinetics, efficacy, safety, or place in therapy of nebivolol/valsartan in human subjects. Data Synthesis: Most patients with HTN require combination therapy; however, β-adrenergic antagonists and AII type 1 receptor blockers have been considered less effective because of overlapping mechanisms of action. A phase III, randomized trial demonstrated that nebivolol/valsartan produced statistically significant blood pressure (BP) lowering as compared with monotherapy with the individual components or placebo. Substudy analyses confirmed this among subgroups and demonstrated that nebivolol/valsartan decreased plasma renin and aldosterone levels. One trial reported continued BP lowering at 52 weeks. Another study showed that nebivolol/valsartan had similar additivity scores as compared with other antihypertensive combinations. Relevance to Patient Care and Clinical Practice: This review discusses drug information, efficacy, and safety of nebivolol/valsartan and discusses its clinical relevance as a novel combination product in managing patients with HTN. Conclusion: Nebivolol/valsartan combination may offer a benefit to patients with an indication for both classes who desire to decrease pill burden. Although BP lowering was statistically significant in comparison to the individual components as monotherapy, the combination does not offer clinically significant benefits that would elevate its place in HTN management.
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