[Why is a combination of basal insulin with a GLP-1 receptor agonist useful in many patients with type 2 diabetes?]

Background: In 2015, the combination of basal insulin and GLP-1 receptor agonist (RA) was incorporated into the guideline recommendations for type 2 diabetes as an option for the last escalation step. The two antidiabetics to be injected subcutaneously are complementary regarding their respective main effects and limitations. Basal insulin is predominantly active between meals and in the fasting state, whereas the main action of GLP-1 RA consists in preventing an excessive postprandial blood glucose increase. Moreover, GLP-1 RA is characterised by a low intrinsic risk of hypoglycaemia, body weight reduction and a positive impact on cardiovascular risk factors. Unlike GLP-1 RA, no upper dose limits are defined for basal insulin. However, initiation of insulin therapy is associated with disadvantages in terms of hypoglycaemia and weight increase. Therefore, patients achieving their treatment goals with GLP-1 RA alone are better treated without insulin.
Method: In a review, study results on combinations of basal insulin and GLP-1-RA versus comparative therapies are presented.
Results: Most of the studies were carried out in patients pre-treated with basal insulin. The add-on of GLP-1 RA was commonly associated with significant reductions of body weight and also resulted in additional HbA _1c reductions compared with an increase of the basal insulin dose. The add-on of a short acting insulin to an existing basal insulin therapy enabled similar HbA _1c reductions to the add-on of a GLP-1 RA, but simultaneously increased the number of episodes of hypoglycaemia and might lead to more unfavourable body weight developments. A fixed combination of insulin degludec and liraglutide (IDegLira) showed an effective and rather steady blood glucose reduction in a 24-hour interval vs. basal insulin or GLP-1 RA alone.
Conclusions: Combinations of basal insulin and a GLP-1 RA improve glycaemic control in many patients with type 2 diabetes without any significant increase of the risk of hypoglycaemia and without weight gain, especially compared to a dose increase of the basal insulin or add-on of a short-acting insulin.