What are the adjunctive therapies, other than insulin, for type 1 diabetes mellitus (Type 1 DM)?

Adjunctive Therapies for Type 1 Diabetes Mellitus

Pramlintide is the only FDA-approved non-insulin adjunctive therapy for type 1 diabetes mellitus (T1DM) patients who have failed to achieve desired glucose control despite optimal insulin therapy. 1, 2

Primary Treatment: Insulin Therapy

• Insulin remains the mainstay of therapy for T1DM due to absent or near-absent β-cell function 3
• Most patients should be treated with multiple daily injections (MDI) of prandial and basal insulin or continuous subcutaneous insulin infusion (CSII) 3
• Rapid-acting insulin analogs are recommended over human insulins to reduce hypoglycemia risk 3
• Patients should be educated on matching prandial insulin doses to carbohydrate intake, premeal blood glucose levels, and anticipated physical activity 3

FDA-Approved Adjunctive Therapy: Pramlintide

• Pramlintide is an injectable amylin analog indicated as adjunctive treatment for T1DM patients who have failed to achieve desired glucose control despite optimal insulin therapy 2
• Mechanism of action: delays gastric emptying, blunts pancreatic glucagon secretion, and enhances satiety 3, 1, 4
• When initiating pramlintide, mealtime insulin doses must be reduced by 50% to minimize the risk of severe hypoglycemia 2, 4
• For T1DM patients, pramlintide should be initiated at 15 mcg subcutaneously before major meals, with gradual titration to 30,45, or 60 mcg as tolerated 2
• Pramlintide should be administered as a separate injection from insulin and should not be mixed with any insulin 2

Pramlintide Considerations and Cautions

• Severe hypoglycemia risk is highest within 3 hours following pramlintide injection 2
• Nausea is a common side effect; dose should be increased only when no clinically significant nausea has occurred for at least 3 days 2
• If significant nausea persists at 45 or 60 mcg, the dose should be decreased to 30 mcg; if 30 mcg is not tolerated, discontinuation should be considered 2
• Pramlintide is contraindicated in patients with hypoglycemia unawareness or recurrent severe hypoglycemia 2

Investigational Adjunctive Therapies (Not FDA-Approved for T1DM)

Metformin

• May reduce insulin requirements (by approximately 6.6 units/day) and lead to small reductions in weight and lipid levels 3, 1
• Does not significantly improve glycemic control in T1DM (absolute A1C reduction of only 0.11%, not statistically significant) 3, 1
• May be considered for overweight/obese T1DM patients with insulin resistance 1, 4

GLP-1 Receptor Agonists

• Not FDA-approved for T1DM but being studied in this population 3, 1
• Liraglutide has shown some benefit in T1DM patients over 52 weeks but was associated with increased adverse events 3, 1
• Potential benefits include weight loss and reduced insulin requirements 1, 4
• Risks include increased hypoglycemia when used with insulin and potential for ketosis 1, 4

SGLT-2 Inhibitors

• Provide insulin-independent glucose lowering by increasing urinary glucose excretion 1
• Major concern is increased risk of euglycemic diabetic ketoacidosis in T1DM patients 1, 4
• Not FDA-approved for T1DM use 1

Clinical Decision-Making Algorithm

1. Optimize insulin therapy first (MDI or CSII) with appropriate education on dose adjustments 3
2. If glycemic targets are not achieved despite optimal insulin therapy:
   • Consider adding pramlintide if patient has adequate hypoglycemia awareness and can adhere to complex regimen 2
   • Reduce mealtime insulin by 50% when initiating pramlintide 2
   • Start at 15 mcg before meals and titrate slowly based on tolerance 2
3. For overweight/obese T1DM patients with signs of insulin resistance:
   • Consider off-label metformin use for its effects on weight and insulin requirements 3, 1

Monitoring Recommendations

• Monitor blood glucose frequently when initiating any adjunctive therapy, particularly before and after meals 2
• Assess for hypoglycemia, especially within 3 hours after pramlintide injection 2
• Evaluate for gastrointestinal side effects, particularly nausea with pramlintide 2
• For off-label therapies, monitor for specific risks (e.g., ketosis with SGLT-2 inhibitors) 1, 4