A comparison of the efficacy and safety of an oral versus an injectable treatment for patients with type 2 diabetes mellitus

This study evaluated whether an oral dose of sitagliptin was as effective as an injectable dose of liraglutide in patients with type 2 diabetes mellitus (T2DM) uncontrolled with metformin alone.

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. This can lead to damage of muscle, blood vessels, and nerve functioning. Along with lifestyle changes including diet and exercise, metformin (Glucophage) is generally the first treatment used for patients with T2DM. However, many patients do not achieve a good blood glucose control under this treatment and other treatments are needed to help them manage the disease and avoid complications. A type of treatment that has been explored for these patients includes incretin-based drugs. Incretins are a type of hormone released naturally after a meal, which causes an increase of insulin released from the pancreas. This leads to a drop in glucose levels after a meal. Incretin-based therapies include drugs such as sitagliptin (Januvia) and liraglutide (Victoza). Both drugs have been previously found to be safe for T2DM patients, along with metformin. The current study compares the safety and efficacy of these drugs in patients with T2DM uncontrolled with metformin only, given the fact that sitagliptin is given by mouth (orally) and liraglutide is administered by injection. 

This study included 522 T2DM patients who were already being treated with metformin. Patients were randomly assigned to receive, in addition to metformin, either oral sitagliptin (269 patients) or injectable liraglutide (253 patients) in increasing doses over 26 weeks. Patients in both groups whose blood sugar levels were not well controlled by week 12 received another glucose lowering drug, glimepiride (Amary).

Patients in both treatment groups had similar decreases in their glycated hemoglobin or HbA1c (a blood test that provides an average of the blood sugar levels from the last 2 to 3 months) levels. Patients in the injectable treatment group had a faster initial reduction in HbA1c levels (-1.4%) compared to patients in the oral therapy group (-1.3%). Also, at the end of the 26 weeks of treatment, more patients in the injectable strategy group had a good blood sugar control (HbA1c level lower that 7%) compared to patients in the oral strategy group (72.3% versus 62.8%). Both treatment groups reported few side effects. Hypoglycemia (abnormally low blood sugar levels) was more common in the oral strategy group, while nausea, vomiting, diarrhea and stomach pain were more frequently reported in the injectable treatment group.

In summary, oral therapy with sitagliptin and metformin is as safe and effective as injectable therapy with liraglutide combined with metformin in patients with T2DM uncontrolled with metformin alone. This study also showed that glimepiride can be a safe addition to either treatment strategy, in case of still uncontrolled disease.

The study was funded by Merck & Co., the manufacturers of Januvia.