Pharmacologic adjunctive to insulin therapies in type 1 diabetes: The journey has just begun

Table 1 Advantages and pitfalls of the use of various therapeutic classes as adjunctive treatments in type 1 diabetes

Therapeutic class	Advantages	Pitfalls
Biguanides (metformin)	Optimal effects on body weight, lipid concentrations and insulin dose	Effect on HbA1C not sustainable over time. Potentially greater risk of hypoglycemia
DPP-4 inhibitors	Immunoregulatory actions. Potential role in preserving beta-cell function. Good safety profile	Non-significant effect on HbA1C
GLP-1 agonists	Significant reductions in HbA1C, body weight and insulin dose (particularly bolus doses)	Greater risk of hypoglycemia and DKA
Amylin analogues (pramlintide)	FDA approved. Significant reductions in HbA1C, body weight and insulin dose (particularly bolus doses)	It should be subcutaneously administered 3-4 times/d
SGLT-2 inhibitors	Optimal effects on HbA1C, body weight, insulin dose and glycemic variability. They do not increase risk of hypoglycemia	Increased risk of DKA and genital tract infections
Thiazolidinediones	Reduction in HbA1C and insulin dose in insulin-resistant T1D patients	Weight gain. Not effective in lean patients

HbA1_C: Glycated hemoglobin A1_C; DPP-4: Dipeptidyl peptidase-4; GLP-1: Glucagon-like peptide-1; FDA: United States Food and Drug Administration; SGLT-2: Sodium-glucose co-transporter 2; T1D: Type 1 diabetes; DKA: Diabetic ketoacidosis.