Safety and efficacy of adding liraglutide and insulin detemir to metformin in patients with type 2 diabetes mellitus

This study evaluated whether a combination of metformin, liraglutide, and insulin detemir is a safe and effective treatment for patients with type 2 diabetes mellitus (T2DM).

Patients with T2DM do not produce enough insulin (or are resistant to insulin) to break down the glucose they take in from food, therefore the glucose builds up in the bloodstream. Metformin (Glucophage) and sulfonylureas (glyburide, glipizide) are usually the first drugs used for the treatment of T2DM patients. However, T2DM is a progressive disease, which means other treatments are eventually needed to help control glucose levels. Currently, there are no specific guidelines for the sequence in which other drugs should be used in addition to metformin. While injected insulin is one choice, another family of drugs that has been considered is glucagon-like peptide-1 receptor agonists (GLP-1RAs). These drugs lower blood glucose by increasing insulin release from the pancreas. The current study examines the long-term safety and efficacy of adding a GLP-1RA (liraglutide) along with insulin detemir (Levemir) to metformin treatment in patients with T2DM. Insulin detemir is a long-acting type of insulin that works slowly over 24 hours. Liraglutide (Victoza) is a long-acting GLP-1RA that is injected under the skin, just like insulin. The blood glucose control from the last 2 to 3 months is measured through the value of the glycated hemoglobin (HbA1c). 

This study included 648 T2DM patients who were first treated with metformin with or without sulfonylurea for 12 weeks. When these drugs alone did not manage to control blood glucose levels, sulfonylurea was then stopped, and liraglutide 1.8mg was added to metformin for another 12 weeks. After the end of these 12 weeks, 323 patients with a HbA1c level greater than 7% (uncontrolled T2DM) were randomly assigned to either continue with metformin and liraglutide (the ML group – 161 patients), or to receive additional insulin detemir to this treatment (the MLI group – 162 patients) until the end of 52 weeks. Patients with HbA1c levels lower than 7% after the initial 12 weeks continued receiving ML treatment (observational group).

In the first 12 weeks of metformin and liraglutide treatment, HbA1c levels decreased with -0.6%. Also, patients lost approximately 3.5 kg during this treatment period. The patients in the MLI group experienced a further -0.5% decrease in HbA1c levels and maintained their weight loss, while patients in the ML group saw no further decrease in HbA1c levels, but continued to lose weight (-1.02 kg) until the end of 52 weeks of treatment. At the end of the study period, 52% of patients in the MLI group had an HbA1c level lower than 7%, compared to 22% of patients in the ML group. At the end of 52 weeks of treatment, 73% of patients in the observational group had achieved HbA1c levels lower than 7%. Rates of adverse events, such as hypoglycemia (abnormally low blood sugar levels) or gastrointestinal problems (nausea, vomiting and diarrhea), were low for all groups.

In summary, this study showed that adding liraglutide and insulin detemir to metformin treatment improved blood glucose control and was safe for patients with T2DM.

The study was funded by Novo Nordisk, the manufacturer of both liraglutide and insulin detemir.

If your T2DM is not being controlled with metformin alone, discuss with your doctor what the best treatment options for your situation might be.