Liraglutide: A Review of Its Use in the Management of Obesity

Abstract

Globally, obesity has reached epidemic proportions and poses an ever increasing burden from a societal and healthpayer perspective. Although lifestyle interventions are fundamental in its management, in the real world setting most obese or overweight adults require adjunctive pharmacotherapy to achieve clinically relevant reductions in bodyweight (i.e. a ≥5 % reduction). Subcutaneous liraglutide (Saxenda(®)) 3 mg once daily is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic bodyweight management in adults with an initial body mass index (BMI) of ≥30 kg/m(2) (obese) or a BMI of ≥27 kg/m(2) (overweight) and at least one bodyweight-related comorbidity [e.g. hypertension, dyslipidaemia, type 2 diabetes mellitus or obstructive sleep apnoea (OSA)]. In phase III trials (32 or 56 weeks' duration) in these populations, subcutaneous liraglutide was associated with clinically relevant reductions in fasting bodyweight and was generally well tolerated. Liraglutide was significantly more effective than placebo in terms of reductions in fasting bodyweight and waist circumference, and improvements in some biomarkers of cardiovascular risk. Improvements in bodyweight were maintained after up 2 years of liraglutide therapy. In nondiabetic adults with moderate to severe OSA, liraglutide improved apnoea-hypopnoea index scores at 32 weeks, which was largely driven by significant reductions in bodyweight. In the absence of head-to-head trials, the relative position of individual anti-obesity drugs remains to be fully determined. In the meantime, liraglutide is an emerging option, as an adjunct to a reduced-calorie diet and increased physical activity, for chronic bodyweight management in obese adults and overweight adults with at least one bodyweight-related comorbidity.

Variables associated with HbA1c and weight reductions when adding liraglutide to multiple daily insulin injections in persons with type 2 diabetes (MDI Liraglutide trial 3)

“… 25 26 A possible explanation for the relation between higher baseline proinsulin and potential greater HbA1c reduction is that GLP-1 RA influences insulin resistance by decreasing visceral abdominal fat. 22 Moreover, it is also possible that the association between proinsulin and HbA1c reduction could be explained by GLP-1 RA working by increasing the processing of proinsulin to insulin in beta cells, something that has been shown in mice. 27 If this is the case, it could be imagined that those with a higher proinsulin level, and thus a higher insulin resistance and beta cell dysfunction, would have the most effect from GLP-1 RA treatment.…”

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

“…Several lines of clinical evidence implicate a role for altered GLP-1 function in the pathophysiology of human obesity and a number of recent clinical trials have validated the clinical efficacy of long-term once daily SC 3 mg liraglutide (Saxenda) as an adjunct to calorie-restriction and exercise counselling in obese and overweight individuals with at least one weight related comorbidity. Significant improvements in clinical outcome measures such as body weight, anthropometric and cardiometabolic parameters, and indices of glucose tolerance have been observed and recently reviewed elsewhere[204]. Though March 2015 saw the EMA grant marketing authorization for 3 mg liraglutide as a weight-management agent in all 28 EU states[45], cost-benefit of funding treatment on the NHS undoubtedly contributes to the uncertainty of launch plans in the United Kingdom at present[46].…”

Liraglutide (Saxenda<sup>®</sup>) as a Treatment for Obesity

“…Native GLP-1 is rapidly degraded by endogenous DPP-4 enzyme promoting a short half-life of 1.5 -2 minutes. Liraglutide is stable against DPP-4 degradation and has a prolonged plasma half-life of 13 hours [15] [16]. Similar to endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor.…”