Poorly Controlled Type 2 Diabetes and GLP-1 RA

November 20, 2015
Leah Lawrence

What happens when T2DM patients on daily insulin add a GLP-1 receptor agonist to their treatment?

Patients with type 2 diabetes (T2DM) who were taking multiple daily insulin injections were able to successfully lower their HbA1c and decrease their insulin dose with the use of the glucagon-like peptide (GLP)-1 receptor agonist liraglutide, according to the results of a study published in BMJ.

Liraglutide was associated with a 1.5% reduction in HbA1c and helped patients to lower their body weight by 3.8 kg compared with placebo, the study showed.

“Improved glycemic control was obtained despite a lowering of insulin doses by 15.8 units in the liraglutide group compared with controls and without any increased risk of hypoglycaemia,” wrote Marcus Lind, of the Institute of Medicine, University of Gothenburg, Sweden, and colleagues.

According to the study, patients with poorly controlled T2DM are often treated with multiple daily insulin injections, a treatment that is associated with weight gain. Lind and colleagues conducted this study to determine if adjunct treatment with liraglutide could lower glucose levels and decrease body weight in patients with T2DM requiring multiple daily injections.

The study included 124 participants with poorly controlled T2DM defined as HbA1c of 7.5% or greater. All patients had a BMI between 27.5 and 45 kg/m2 and required multiple daily insulin injections. The participants were randomly assigned to liraglutide or placebo.

The primary endpoint of the study was the change in HbA1c from baseline to week 24. Patients assigned liraglutide had a mean reduction of 16.9 mmol/mol (1.5% HbA1c) compared with 4.57 mmol/mol (0.4% HbA1c) for placebo (P<0.001). In addition, significantly more patients assigned liraglutide reached an HbA1c of less than 7% (42.9% vs. 5.1%; P<0.001).

Participants assigned to liraglutide had a mean reduction in body weight of 3.8 kg compared with no reduction among participants assigned placebo (P<0.001). Treatment with liraglutide also resulted in a mean reduction in daily insulin dose of 18.1 units compared with 2.3 units for patients assigned placebo (P<0.001).

“Besides improvement in glycemic control and weight reduction, participants experiencing large fluctuations in glucose levels could benefit from the addition of liraglutide to their treatment regimen,” the researchers wrote. “In our study, the standard deviation of glucose levels was significantly reduced after treatment with liraglutide.”

No severe hypoglycemic events occurred in either group and no difference in symptomatic or asymptomatic non-severe hypoglycemia occurred.

“Importantly, the aim of the current trial was to study the effects of adding liraglutide to multiple daily insulin injections and continuing regular treatment of people with type 2 diabetes. Hence insulin doses were not adjusted by investigators except for safety, although participants were instructed to continue to adjust doses,” the researchers wrote. “Thus the results of the present study may differ from those of a trial using a treat to target design, where insulin doses can be optimized by investigators simultaneous to adding liraglutide.”

Reference: Lind M, et al. Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections: randomized clinical trial (MDI Liraglutide trial). BMJ. 2015;351:h5364.