When long-acting insulin is no longer enough: comparing the addition of liraglutide or short-acting insulin

This study compared the addition of the new drug liraglutide (Victoza) to the addition of short-acting insulin in type 2 diabetics already treated with long-acting insulin and metformin.

Type 2 diabetes is a progressive disease. In the beginning patients may be able to control their blood glucose (sugar) with lifestyle changes. However, they will most likely need glucose lowering medications, such as metformin (Glucophage), and eventually basal insulin (a long-acting insulin given once a day). As the disease progresses, insulin dosages will also need adjusting. The American Diabetes Association generally recommends adding bolus insulin (short-acting) prior to every meal, which can be a difficult transition for some patients. For some patients, adding a bolus insulin dose prior to the largest meal of the day may be sufficient for blood glucose (sugar) control.

Liraglutide is a new treatment for type 2 diabetes. It activates the Glucagon-like peptide-1 (GLP-1) receptor, which leads to increased release of insulin by the body. This type of therapy can be used in addition to basal insulin and metformin. However, adding liraglutide has not been compared to adding short-acting, bolus insulin before meals.

This study compared adding liraglutide or short-acting insulin (insulin aspart [NovoLog]) to long-acting basal insulin (insulin degludec [Tresiba]) and metformin. 177 patients were included in the study and followed for 26 weeks: 88 added liraglutide and 89 added insulin aspart. 236 patients using only insulin degludec were also included as a comparison group. HbA1c (average blood glucose levels over three months) and fasting glucose levels (glucose level after a period without food or drink) were measured throughout the trial. Patients also performed daily blood glucose monitoring. Adverse events and episodes of hypoglycemia (dangerously low blood glucose) were recorded.

The addition of liraglutide led to a 0.74% decrease in HbA1c levels from the start of the study to week 26, while the addition of insulin aspart led to a 0.39% decrease. The decrease in HbA1c levels was significantly greater in patients receiving liraglutide than those receiving insulin aspart (a 0.32% difference).

The number of patients who achieved HbA1c levels less than 7.0% did not differ between the two groups. However, patients receiving liraglutide were 13.79 times more likely to do so without experiencing hypoglycemia. There were not significant differences in fasting glucose levels between the two groups.

Patients in the liraglutide group lost an average of 2.8 kg (6.2 lbs), compared to the insulin aspart group, who gained an average of 0.9 kg (2 lbs). However, liraglutide led to more gastrointestinal side effects than insulin aspart.

Of the patients who continued treatment with only the long-acting insulin, 80.5% maintained an HbA1c of less than 7.0% at the end of 26 week, and 60.4% did so without experiencing hypoglycemia.

This study concluded that the addition of liraglutide to a treatment regimen of long-acting insulin and metformin can improve average blood glucose, with less hypoglycemia and more weight loss compared to the addition of a short-acting insulin.   

The study was sponsored by Novo Nordisk, who also developed the drug Liraglutide.