Short‐acting glucagon‐like peptide‐1 receptor agonists as add‐on to insulin therapy in type 1 diabetes: A review

A large proportion of patients with type 1 diabetes do not reach their glycaemic target of glycated hemoglobin (HbA1c) <7.0% (53 mmol/mol) and, furthermore, an increasing number of patients with type 1 diabetes are overweight and obese. Treatment of type 1 diabetes is based on insulin therapy, which is associated with well‐described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because of their glucagonostatic and extrapancreatic effects. So far, the focus has mainly been on the long‐acting GLP‐1RAs, but the risk–benefit ratio emerging from studies evaluating the effect of long‐acting GLP‐1RAs as adjunctive therapy to insulin therapy in patients with type 1 diabetes has been disappointing. This might be attributable to a lack of glucagonostatic effect of these long‐acting GLP‐1RAs in type 1 diabetes, alongside development of tachyphylaxis to GLP‐1‐induced retardation of gastric emptying. In contrast, the short‐acting GLP‐1RAs seem to have a preserved and sustained effect on glucagon secretion and gastric emptying in patients with type 1 diabetes, which could translate into effective lowering of postprandial glucose excursions; however, these observations regarding short‐acting GLP‐1RAs are all derived from small open‐label trials and should thus be interpreted with caution. In the present paper we review the potential role of GLP‐1RAs, in particular short‐acting GLP‐1RAs, as add‐on to insulin in the treatment of type 1 diabetes.