Adjunctive therapy for glucose control in patients with type 1 diabetes

Abstract

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.

Characterizing the weight-glycemia phenotypes of type 1 diabetes in youth and young adulthood

“…Clinical recommendations for individuals with HbA1c levels above target may differ based on weight status, especially given the complicated physiologic relationships between weight and glycemia 31. For example, approaches for under or normal weight individuals with elevated HbA1c may be centered on insulin intensification, while approaches for overweight individuals could balance the glycemic benefits of insulin intensification with the potential for weight gain via concurrent behavioral, pharmacological, or surgical interventions 32. Although the American Diabetes Association Standards of Care currently state that the risks and benefits of agents adjunctive to insulin therapy in T1D require further evaluation, early studies have shown improvements in glycemic control as well as body weight associated with metformin, GLP1-receptor agonists, and SGLT-2 inhibitors 32 33.…”

“…For example, approaches for under or normal weight individuals with elevated HbA1c may be centered on insulin intensification, while approaches for overweight individuals could balance the glycemic benefits of insulin intensification with the potential for weight gain via concurrent behavioral, pharmacological, or surgical interventions 32. Although the American Diabetes Association Standards of Care currently state that the risks and benefits of agents adjunctive to insulin therapy in T1D require further evaluation, early studies have shown improvements in glycemic control as well as body weight associated with metformin, GLP1-receptor agonists, and SGLT-2 inhibitors 32 33. Subgroups with adequate glycemic control and overweight or obesity may be specifically targeted for more intensive behavioral modifications such as dietary interventions to address obesity with special attention towards avoiding hypoglycemia associated with decreased caloric or carbohydrate intake 31.…”

“…Ultimately, larger and intentionally designed trials will be required to move from understanding observational phenotypes to devising their therapeutic approaches. In particular, as the treatment landscape of T1D expands to include novel non-insulin adjuvants32 as well as hybrid closed loop and fully automated insulin delivery systems,34 capturing treatment response across subgroups both in terms of changes in body weight and glycemic control will provide critical data to inform how phenotypes may be modified to better predict heterogeneity in response to specific treatment approaches.…”

Incretins today: multiple effects and therapeutic potential

“…Ряд пилотных работ с применением инкретиновой модели терапии при СД 1 типа был весьма оптимистичен [49,50]. В патогенезе поздних осложнений СД 1 типа, в частности диабетической нефропатии, с успехом изучались и протекторные негликемические эффекты ГПП-1, включая даже тех пациентов, которые получали заместительную почечную терапию программным гемодиализом или перенесли трансплантацию почки [51].…”

Understanding of type 1 diabetes mellitus: what we know and where we go

“…Although insulin technology and its administration have shown remarkable advances, individuals with T1DM have continued difficulties in maintaining target glucose levels and sometimes suffer AE, such as severe hypoglycemia and weight gain [ 61 ]. Therefore, the evaluation of adjunctive therapies in individuals with T1DM is required.…”