Non-insulin drugs to treat hyperglycaemia in type 1 diabetes mellitus

Lancet Diabetes Endocrinol. 2016 Sep;4(9):766-780. doi: 10.1016/S2213-8587(16)00039-5. Epub 2016 Mar 9.


Insulin treatment of individuals with type 1 diabetes has shortcomings and many patients do not achieve glycaemic and metabolic targets. Consequently, the focus is on novel non-insulin therapeutic approaches that reduce hyperglycaemia and improve metabolic variables without increasing the risk of hypoglycaemia or other adverse events. Several therapies given in conjunction with insulin have been investigated in clinical trials, including pramlintide, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter inhibitors, metformin, sulfonylureas, and thiazolidinediones. These drugs have pleiotropic effects on glucose metabolism and different actions complementary to those of insulin-this Review reports the effects of these drugs on glycaemic control, glucose variability, hypoglycaemia, insulin requirements, and bodyweight. Existing studies are of short duration with few participants; evidence for the efficacy of concomitant treatments is scarce and largely clinically insignificant. A subgroup of patients with type 1 diabetes for whom non-insulin antidiabetic drugs could significantly benefit glycaemic control cannot yet be defined, but we suggest that obese patients prone to hypoglycaemia and patients with residual β-cell function are populations of interest for future trials.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / etiology
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use*
  • Islet Amyloid Polypeptide / therapeutic use
  • Metformin / therapeutic use
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use


  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Islet Amyloid Polypeptide
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Metformin
  • pramlintide