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Liraglutide, an antiobesity pharmacotherapy

Liraglutide is a human glucagon-like peptide 1 analog that may be administered once a day because of its prolonged half-life of 13 hours.

Liraglutide was developed to improve glycemic control in patients with type 2 diabetes. The efficacy of the drug was well established in the Liraglutide Effect and Action in Diabetes ( LEAD ) studies, a series of phase III randomized, controlled trials.
The approved doses for the treatment of diabetes are 1.2 and 1.8 mg in the United States and 0.6 and 0.9 mg in Japan.
The LEAD-3 trial comprised 746 patients with type 2 diabetes assigned to Liraglutide ( 1.2 or 1.8 mg ) or Glimepiride ( 8 mg ) treatment groups for 52 weeks. The HbA1c reductions from baseline were -0.84% and -1.14% in the 1.2 and 1.8 mg groups, respectively, and body weight was reduced by -2.05 kg from baseline in the 1.2 mg group and -2.45 kg in the 1.8 mg group, whereas a significant weight gain ( 1.12 kg ) was observed in patients treated with Glimepiride.
A consistent reduction in body weight was observed across the LEAD trials.

Liraglutide ( Saxenda ) has been approved by FDA ( Food and Drug Administration ) for the treatment of obesity. The recommend dose is 3 mg in contrast to 1.2 or 1.8 mg for diabetes.
The Satiety and Clinical Adiposity-Liraglutide Evidence in Nondiabetic and Diabetic Subjects ( SCALE ) trial consists of four clinical trials designed to demonstrate the safety and efficacy of Liraglutide 3 mg for weight management.

The SCALE Obesity and Prediabetes phase IIIa trial involving 3,731 patients found that patients treated with Liraglutide lost an average of 8% of their body weight in 56 weeks compared with 2.6% in the placebo group.
Moreover, significantly more patients in the Liraglutide group lost greater than or equal to 5% of their baseline body weight compared with those taking the placebo ( 63.5% vs 26.6%, respectively ), and 32.8% of the Liraglutide group lost more than 10% of their baseline body weight ( 10.1% in the placebo group ).

The SCALE-Diabetes trial was a 56-week randomized, placebo-controlled trial designed to investigate the potential of Liraglutide 3 mg in obese or overweight patients with type 2 diabetes.
In this trial, 846 overweight or obese patients with diabetes mellitus were assigned randomly to Liraglutide 3 mg or 1.8 mg or placebo groups. After 56 weeks, the 3 and 1.8 mg Liraglutide groups achieved weight loses of 6% and 5%, respectively, compared with 2% in the placebo group.
Furthermore, 50% of the patients in the 3 mg group and 35% of those in the 1.8 mg group achieved greater than or equal to 5% weight loss compared with 13% in the placebo group, and approximately 69% of the patients treated with Liraglutide 3 mg achieved the HbA1c target of less than 7%.

Concerned by the lack of long-term data for Liraglutide in the treatment of obesity and a variety of safety issues, such as gallbladder disease, pancreatitis, breast and thyroid cancers, and increased heart rate, the FDA Advisory Panel recommended that these issues be addressed in postmarketing studies.
However, the Panel agreed that the ongoing cardiovascular outcomes trial of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results ( LEADER ) study would be sufficient to characterize the cardiovascular risk of the Liraglutide. ( Xagena )

Won Seon Jeon and Cheol-Young Park, Endocrinol Metab 2014; 29: 410–417