Introduction of liraglutide

Liraglutide is a glucagon-like peptide-1 (GLP-1) agonist that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of obesity with 3.0 mg of liraglutide once daily. It increases insulin concentrations after eating before blood sugar levels rise. It is also used to treat type 2 diabetes and prevent cardiovascular complications associated with diabetes.

Liraglutide and Non-Diabetic Obese Adults

A study evaluated the efficacy at 12 weeks of low-dose liraglutide on the weight of Taiwanese patients without T2D. Compared to baseline, 5.6% of patients in the liraglutide 1.2 mg group reached weight reduction (p<0.001), whereas in the 0.6 mg group 6.4% reached weight reduction (p<0.001). However, there was no difference in weight reduction between liraglutide doses (absolute difference 1.2 mg vs. 0.6 mg ?0.8%, 95%CI ?0.12 to 0.11).

In a study evaluating the efficacy of liraglutide in non-diabetic obese adults by Joshuan J et al. Twelve RCTs (n = 8249) were included. In comparison to placebo, liraglutide reduced body weight (MD ?3.35 kg; 95%CI ?4.65 to ?2.05; p < 0.0001), and BMI (MD ?1.45 kg/m2 ; 95%CI ?1.98 to ?0.91; p < 0.0001). Liraglutide did not reduce TEAEs (RR 1.08; 95%CI 0.92 to 1.27; p = 0.25), and Hb1Ac (MD ?0.76%; 95%CI ?2.24 to 0.72; p = 0.31). Furthermore, it did not increase hypoglycemic episodes (RR 2.01; 95%CI 0.37 to 11.02; p = 0.28). Finally, liraglutide reduced systolic blood pressure (MD ?3.07 mmHg; 95%CI ?3.66 to ?2.48; p < 0.0001) and diastolic blood pressure (MD ?1.01 mmHg; 95%CI ?1.55 to ?0.47; p = 0.0003). Seven RCTs had a high risk of bias. Subgroup analyses by length of treatment and doses had effects similar to the overall analyses. Quality of evidence was low or very low for most outcomes.

CONCLUSION: In non-diabetic obese adults, liraglutide reduced body weight, BMI and blood pressure compared with placebo. incidence of TEAEs, Hb1Ac and hypoglycaemia did not differ from placebo.Liraglutide treatment resulted in clinically relevant (?5%) weight loss in 48.2%-88.7% of obese/overweight adults without diabetes. Liraglutide was associated with weight loss and was well tolerated.

Mechanism of action

Liraglutide is an agonist at the glucagon-like peptide-1 receptor coupled to adenylate cyclase. Increases in cyclic AMP stimulate glucose-dependent release of insulin, inhibit glucose-dependent release of glucagon, and slow gastric emptying to increase control of blood glucose.

References:

[1] BARBOZAJOSHUAN J. Efficacy of Liraglutide in Non-Diabetic Obese Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.[J]. Journal of Clinical Medicine, 2022, 11 11. DOI:10.3390/jcm11112998.

[2] DENGYOU. Effect of semaglutide and liraglutide in individuals with obesity or overweight without diabetes: a systematic review.[J]. Therapeutic Advances in Chronic Disease, 2022: 20406223221108064. DOI:10.1177/20406223221108064.