Pharmacological Approach to Type 1 Diabetes in Adults

- Introduction

Insulin treatment is crucial for individuals with type 1 diabetes due to absent or near-absent β-cell function, which can lead to hyperglycemia, metabolic disturbances, and life-threatening tissue catabolism. The Diabetes Control and Complications Trial (DCCT) found that intensive therapy reduced A1C and improved long-term outcomes, but was associated with a higher rate of severe hypoglycemia. Insulin replacement plans typically consist of basal insulin, mealtime insulin, and correction insulin. Basal insulin analogs have longer duration of action and are associated with less hypoglycemia and weight gain. However, the cost and intensity of treatment may be prohibitive. Regular reassessment of insulin-taking behavior and adjustment of treatment plans are recommended. Individuals with type 1 diabetes require approximately 30-50% of their daily insulin as basal and the remainder as prandial, with total daily insulin requirements ranging from 0.4 to 1.0 units/kg/day. For examples of subcutaneous insulin treatment plans (Regimens) see annexes table 1.

Noninsulin Treatments for Type 1 Diabetes

Injectable and oral glucose-lowering medications have been studied for their efficacy as adjunct to insulin treatment of type 1 diabetes. Pramlintide is based on the naturally occurring β-cell peptide amylin and is approved for use in adults with type 1 diabetes. Clinical trials have demonstrated a modest reduction in A1C (0.3–0.4%) and modest weight loss (∼1 kg) with pramlintide Similar results have been reported for several agents currently approved only for the treatment of type 2 diabetes. The addition of metformin in adults with type 1 diabetes was associated with small reductions in body weight, insulin dose, and lipid levels but did not sustainably improve A1C. The largest clinical trials of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in type 1 diabetes have been conducted with Liraglutide 1.8 mg daily, and results showed modest A1C reductions (∼0.4%), decreases in weight (∼5 kg), and reductions in insulin doses . Similarly, sodium–glucose co-transporter 2 (SGLT2) inhibitors have been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C, reduced body weight, and improved blood pressure . However, SGLT2 inhibitor use in type 1 diabetes was associated with an increased rate of DKA. 

Surgical Treatment for Type 1 Diabetes

Pancreas and Islet Transplantation

Successful pancreas and islet transplantation can normalize glucose levels and mitigate microvascular complications of type 1 diabetes. However, people receiving these treatments require lifelong immunosuppression to prevent graft rejection and/or recurrence of autoimmune islet destruction. Given the potential adverse effects of immunosuppressive therapy, pancreas transplantation should be reserved for people with type 1 diabetes undergoing simultaneous kidney transplantation, following kidney transplantation, or for those with recurrent ketoacidosis or severe hypoglycemia despite intensive glycemic management.