Novel anti-obesity drugs

There is increasing evidence that body weight is homeostatically regulated and that in obesity this regulation maintains weight at a high level. Weight loss activates mechanisms that are designed to return individuals to their pre-existing weight. This explains the universally poor results of current strategies to maintain weight loss. On this basis, life-long drug therapy may be justified for those with significant obesity. Currently available drugs include selective serotonin re-uptake inhibitors (e.g., fluoxetine), noradrenergic re-uptake inhibitors (e.g., phentermine), a serotonin and noradrenergic re-uptake inhibitor (sibutramine) and an intestinal lipase inhibitor (orlistat). An active research program is underway to develop new agents based on the rapidly expanding knowledge of the complex mechanisms regulating body weight. Leptin, a hormone produced by adipocytes that inhibits food intake, has undergone clinical trials and analogues are currently being developed. Other agents include amylin, melanocortin-4 receptor agonists, neuropeptide Y antagonists, beta(3) adrenergic agonists and glucagon-like peptide-1 agonists. As some redundancy exists in the central regulatory system controlling body weight, some agents might need to be used in combination to be effective.     

Academy for Eating Disorders International Conference on Eating Disorders

The focus of this meeting was the interface between eating disorders and obesity. A symposium at this meeting dealt with advances in treatment for bulimia nervosa (BN) and binge eating disorder. There were two presentations in this symposium that addressed pharmacological treatments. One reviewed drug treatments for BN, which included reviewing the evidence for the efficacy of tricyclic antidepressants, monoamine oxidase inhibitors and selective serotonin inhibitors in the treatment of BN. All drug studies demonstrated greater reduction in binge eating and purging than with placebo. Other medications studied without evidence of efficacy for BN include opiate antagonists, lithium and anticonvulsants. Two promising agents for BN that require further study are odansitron and topiramate. For binge eating disorder, studies have examined the efficacy of antidepressants (tricyclic antidepressants, selective serotonin re-uptake inhibitors and serotonin/noradrenaline re-uptake inhibitors), antiobesity agents (sibutramine) and antiepileptics associated with weight loss (topiramate), with some evidence of efficacy for these agents.     

Academy for Eating Disorders International Conference on Eating Disorders. Denver,CO, USA,May 29-31, 2003

The focus of this meeting was the interface between eating disorders and obesity. A symposium at this meeting dealt with advances in treatment for bulimia nervosa (BN) and binge eating disorder. There were two presentations in this symposium that addressed pharmacological treatments. One reviewed drug treatments for BN, which included reviewing the evidence for the efficacy of tricyclic antidepressants, monoamine oxidase inhibitors and selective serotonin inhibitors in the treatment of BN. All drug studies demonstrated greater reduction in binge eating and purging than with placebo. Other medications studied without evidence of efficacy for BN include opiate antagonists, lithium and anticonvulsants. Two promising agents for BN that require further study are odansitron and topiramate. For binge eating disorder, studies have examined the efficacy of antidepressants (tricyclic antidepressants, selective serotonin re-uptake inhibitors and serotonin/noradrenaline re-uptake inhibitors), antiobesity agents (sibutramine) and antiepileptics associated with weight loss (topiramate), with some evidence of efficacy for these agents.     

Enhanced selective serotonin re-uptake inhibitors as antidepressants: 2004 – 2006

Depression is a major psychiatric disorder. It affects millions of people worldwide and inflicts tremendous economic burden on societies. The advent of selective serotonin re-uptake inhibitors as antidepressants has been a revolutionary advance in the treatment of depression and related disorders. However, selective serotonin re-uptake inhibitors are also associated with several undesirable properties, such as delayed onset of action, low response rate and side effects. The present search for a newer generation of antidepressants is focused on overcoming these issues. The patent literature covered in this review, during 2004 – 2006, illustrates several strategies employed by the pharmaceutical industry in the development of enhanced serotonin re-uptake inhibitors. Encouraged by the success of venlafaxine and duloxetine, several companies have pursued dual-acting serotonin and noradrenaline re-uptake inhibitors as drug candidates for depression treatment. Molecules with combined serotonin re-uptake inhibitor and 5-HT autoreceptor (5-HT_1A and/or 5-HT_1B) antagonist properties are being developed. In particular, recent research suggests that serotonin 5-HT_1B antagonists alone or combined with selective serotonin re-uptake inhibitors might hold unique promise as efficacious antidepressants. Finally, efforts are underway to formulate new drug candidates with both serotonin re-uptake inhibitor and neurokinin 1 (NK₁) antagonist activities. Despite mixed results from clinical trials with several NK₁ antagonists, effective therapeutic agents for depression may still emerge from compounds with combined serotonin reuptake inhibitor/NK₁ antagonist properties.     

The other face of depression, reduced positive affect: the role of catecholamines in causation and cure

Despite significant advances in pharmacologic therapy of depression over the past two decades, a substantial proportion of patients fail to respond or experience only partial response to serotonin re-uptake inhibitor antidepressants, resulting in chronic functional impairment. There appears to be a pattern of symptoms that are inadequately addressed by serotonergic antidepressants - loss of pleasure, loss of interest, fatigue and loss of energy. These symptoms are key to the maintenance of drive and motivation. Although these symptoms are variously defined, they are consistent with the concept of ;decreased positive affect'. Positive affect subsumes a broad range of positive mood states, including feelings of happiness (joy), interest, energy, enthusiasm, alertness and self-confidence. Although preliminary, there is evidence to suggest that antidepressants that enhance noradrenergic and dopaminergic activity may afford a therapeutic advantage over serotonergic antidepressants in the treatment of symptoms associated with a reduction in positive affect. Dopaminergic and noradrenergic agents, including the dual acting norepinephrine and dopamine re-uptake inhibitors, have demonstrated antidepressant activity in the absence of serotonergic function, showing similar efficacy to both tricyclic and serotonin re-uptake inhibitor antidepressants. Moreover, the norepinephrine and dopamine re-uptake inhibitor bupropion has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Focusing treatment on the predominant or driving symptomatology for an individual patient with major depression could potentially improve rates of response and remission.     

Fluvoxamine: a selective serotonin re-uptake inhibitor for the treatment of obsessive-compulsive disorder

Fluvoxamine is the selective serotonin re-uptake inhibitor with the largest database in the treatment of obsessive-compulsive disorder, a severe, and often chronic, anxiety disorder associated with substantial impairment in functioning. The selective serotonin re-uptake inhibitors represent a first-line treatment in patients with obsessive-compulsive disorder. These agents work primarily by blocking the re-uptake of serotonin into the presynaptic nerve terminal, which is believed to be mediated by their effects on the serotonin transport system. In the last two decades, the anti-obsessional effect of fluvoxamine has been tested in several double-blind, placebo-controlled and active-comparison studies, demonstrating its superior efficacy over obsessions and compulsions compared with non-serotonergic antidepressants (i.e., desipramine) and equal efficacy to clomipramine (a tricyclic antidepressant with potent serotonin re-uptake inhibition) and other selective serotonin re-uptake inhibitors (paroxetine and citalopram). However, compared with clomipramine, the selective serotonin re-uptake inhibitor fluvoxamine showed fewer side effects and better tolerability. This reflects the poor affinity of this compound for adrenergic, muscarinic, cholinergic or histaminergic receptors.     

Fluvoxamine: a selective serotonin re-uptake inhibitor for the treatment of obsessive-compulsive disorder

Fluvoxamine is the selective serotonin re-uptake inhibitor with the largest database in the treatment of obsessive-compulsive disorder, a severe, and often chronic, anxiety disorder associated with substantial impairment in functioning. The selective serotonin re-uptake inhibitors represent a first-line treatment in patients with obsessive-compulsive disorder. These agents work primarily by blocking the re-uptake of serotonin into the presynaptic nerve terminal, which is believed to be mediated by their effects on the serotonin transport system. In the last two decades, the anti-obsessional effect of fluvoxamine has been tested in several double-blind, placebo-controlled and active-comparison studies, demonstrating its superior efficacy over obsessions and compulsions compared with non-serotonergic antidepressants (i.e., desipramine) and equal efficacy to clomipramine (a tricyclic antidepressant with potent serotonin re-uptake inhibition) and other selective serotonin re-uptake inhibitors (paroxetine and citalopram). However, compared with clomipramine, the selective serotonin re-uptake inhibitor fluvoxamine showed fewer side effects and better tolerability. This reflects the poor affinity of this compound for adrenergic, muscarinic, cholinergic or histaminergic receptors.     

Selective serotonin re-uptake inhibitors decrease schedule-induced polydipsia in rats: a potential model for obsessive compulsive disorder

Schedule-induced polydipsia was used to determine the effects of selective serotonin re-uptake inhibitors on adjunctive water consumption. Polydipsia was induced in food deprived rats by exposure to a fixed time feeding schedule (FT=60 s) for 150 min per day for 22 days. Selected polydipsic rats consumed 3–4 times greater volume of water compared to food deprived control rats. Chronic administration of the selective serotonin re-uptake inhibitors fluoxetine and clomipramine (CMI) at 5 mg/kg per day and fluvoxamine at 10 mg/kg twice a day significantly decreased schedule-induced polydipsia (SIP) on day 15 and throughout the remainder of the study compared to control rats. The noradrenergic re-uptake inhibitor, desipramine (DMI), only decreased SIP behavior on day 1. The neuroleptic, haloperidol (0.03 and 0.1 mg/kg), and the benzodiazepine, diazepam (2.5 mg/kg), failed to alter SIP behavior. Since obsessive-compulsive disorder (OCD) and polydipsic behavior both involve excessive expression of a normal behavior, the polydipsia model may be relevant for the prediction of compounds useful in the treatment of OCD.     

Some effects of dopamine transporter and receptor ligands on discriminative stimulus, physiologic, and directly observable indices of opioid withdrawal in rhesus monkeys

Rationale  Some monoamine uptake inhibitors (e.g., cocaine) attenuate the subjective and discriminative stimulus effects of opioid withdrawal. Objective  This study examined a role for dopamine transporters and receptors as targets for drugs to modify the discriminative stimulus effects of opioid withdrawal and further examined a subset of these drugs for their capacity to modify some directly observable and physiologic indices of withdrawal. Materials and methods  Rhesus monkeys receiving 2 mg/kg/day of l-α-acetylmethadol discriminated the opioid antagonist naltrexone (0.0178 mg/kg s.c.). Results  The naltrexone discriminative stimulus was attenuated not only by the μ agonist morphine but also by the dopamine D₂-like receptor agonists bromocryptine and quinpirole. In contrast, the naltrexone discriminative stimulus was not consistently modified by the non-selective, D₁- and D₂-like agonist apomorphine or by uptake inhibitors with high selectivity for dopamine transporters (GBR 12909, RTI 113, and RTI 177). In the same monkeys, naltrexone dose dependently decreased body temperature, increased breathing frequency, and induced directly observable signs (grimacing, salivation, and unusual posture). Hypothermia, hyperventilation, and signs of withdrawal were significantly attenuated by morphine and not by quinpirole. Conclusions  Attenuation of opioid withdrawal by D₂-like receptor agonists that have lower efficacy than dopamine, and not by uptake inhibitors with selectivity for dopamine transporters, suggests that magnitude of receptor stimulation (e.g., efficacy) and selectivity at dopamine receptors are important factors in the modulation of opioid withdrawal. Attenuation of the naltrexone discriminative stimulus by drugs that inhibit both dopamine and serotonin uptake (e.g., cocaine) could result from an inhibitory effect of serotonin on dopamine. The role of dopamine in opioid withdrawal appears to be restricted to subjective (i.e., not somatic). An erratum to this article can be found at     

Clinical use of sibutramine

Since obesity is a chronic disorder, a long-term approach is essential, and modern obesity pharmacotherapy means medicating as an adjunct to diet and physical activity not only to achieve weight loss, but also to maintain it. Sibutramine is a US Food and Drug Administration- and European Committee for Proprietary Medicinal Products-approved medication with demonstrated efficacy in long-term obesity management. It is a norepinephrine-serotonin reuptake inhibitor and produces weight loss by a dual mechanism: reduction of food intake and increase in energy expenditure. Sibutramine is given once daily in doses ranging from 5-15 mg. The amount of weight lost with sibutramine is related to both the dose of the drug and the intensity of the behavioral therapy component. Sibutramine produces a weight loss from baseline of more than 5% in over 75% of patients who are prescribed 15 mg daily, and it produces weight loss that averages 5-8% from baseline, independently of the behavioral approach. Weight loss with sibutramine is associated with improvement in waist circumference, lipids, glycemic control, uric acid and health-related quality of life. Sibutramine use is associated with small increases in mean resting blood pressure, but the individual response is variable and not all patients will have blood pressure increases. The drug is also associated with small increases in mean heart rate and should therefore not be used in patients with a history of cardiac arrhythmia. Because it is a serotonin and norepinephrine reuptake inhibitor, sibutramine should not be used with monoamine oxidase inhibitors or noradrenergic agents, and caution is advised in prescribing sibutramine to patients on selective serotonin reuptake inhibitor antidepressants. Given the growing appreciation for the health benefits that can be achieved with even a relatively small weight loss, physicians must become adept in office approaches to achieve modest weight loss. Sibutramine is a useful adjunct to diet and physical activity approaches and can help selected patients achieve and maintain weight loss with concomitant health benefits.     

Serotonergic anti-obesity agents: past experience and future prospects

The role of serotonin (5-hydroxytryptamine) in appetite control is long established. Serotonergic manipulations reduce food intake in rodents in a manner consistent with satiety. In humans, drugs such as fenfluramine, dexfenfluramine and sibutramine all reduce energy intake, suppress hunger and enhance satiety. Effects on eating behaviour and subjective sensations of appetite are associated with the weight loss-inducing effects of these treatments. Currently, no appetite-suppressing drugs are approved specifically for the treatment of obesity. However, a new generation of serotonergic drugs have progressed through clinical development. The serotonin 5-HT(2C)-receptor selective agonist lorcaserin, a drug specifically developed to target satiety without producing the side effect profiles of its predecessors, has been shown to significantly reduce energy intake and body weight. The weight loss produced by lorcaserin appears modest, and behavioural effects, particularly its supposed satiety-enhancing effects, have yet to be characterized. The monoaminergic re-uptake inhibitor tesofensine has also been shown to produce impressive weight loss in smaller-scale clinical studies. It remains unclear if this drug produces any effects on appetite mediated by serotonin, or whether weight loss is produced largely through enhanced energy expenditure. Evidence indicates that tesofensine strengthens satiety, but behavioural specificity and psychological side effects remain an issue. The serotonergic system remains a viable target for anti-obesity treatment. In this review, we examine the limited behavioural data available on these two new CNS-acting appetite suppressants.     

Extended-release bupropion: an antidepressant with a broad spectrum of therapeutic activity?

Bupropion, a noradrenaline and dopamine re-uptake inhibitor, has long been indicated for the treatment of depression. Recent studies have demonstrated additional benefits in depression, including: prevention of the recurrence of seasonal affective disorder in depressive subtypes with decreased energy, pleasure and interest; in major depression with concomitant anxiety; in elderly depressed patients; for non-response to initial serotonin re-uptake inhibitor therapy or augmentation of partial efficacy with serotonin re-uptake inhibitors; and in bipolar depression. Efficacy in other conditions has also been shown in studies of attention deficit hyperactivity disorder, nicotine dependence, obesity and hypoactive sexual desire disorder. Thus, bupropion has proven effective across a broad spectrum of depressive conditions, subtypes and comorbidities.     

Review article: functional dyspepsia—should treatment be targeted on disturbed physiology?

In patients who present with chronic unexplained upper abdominal pain or discomfort (functional dyspepsia), therapy should ideally be targeted on correcting the individual's disturbed pathophysiology. Here, putative mechanisms implicated in functional dyspepsia and potential approaches to therapy are critically reviewed in order to determine if targeting treatment is of value. Pharmacological therapies reviewed include those that aim to correct disordered gastric emptying (e.g. cisapride, dopaminergic receptor antagonists, macrolides), reduce visceral hypersensitivity (e.g. somatostatin analogues, cholecystokinin antagonists, opioid agonists, serotonin type 3 receptor antagonists), reduce gastric acid secretion (e.g. H₂-blockers, acid pump inhibitors), cure Helicobacter pylori infection, enhance muscosal defence (e.g. sucralfate, bismuth) or modify central nervous system processes. It is concluded that the imperfectly understood pathophysiology of functional dyspepsia contributes to the paucity of established efficacious therapies.     

Vane’s blood-bathed organ technique adapted to examine the endothelial effects of cardiovascular drugs in vivo

This study describes a modification of Vane’s blood-bathed organ technique (BBOT). This new technique consisted of replacing the cascade of contractile smooth muscle organs within the traditional BBOT by a single collagen strip cut from a rabbit’s hind leg tendon. Utilizing the extracorporeal circulation of an anesthetized heparinized mongrel cat or Wistar rat, arterial blood was dripped (1–3 ml min^–1) over a collagen strip. This resulted in a gain in weight of the strip, which was due to the deposition of platelet aggregates and a few blood cells trapped over the strip. Arterial blood that had been used for the superfusion was pumped back into the animal’s venous system. However, when this technique is adapted to human volunteers, the superfusing blood should be discarded. In animal experiments, intravenous injections of a variety of classic fibrinolytic agents (e.g., streptokinase) promoted the formation of platelet thrombi. Nitric oxide donors (e.g., SIN-1) at non-hypotensive doses hardly affected the mass of platelet thrombi deposited over the collagen strip, whereas endogenous prostacyclin (e.g., released from vascular endothelium by bradykinin) or exogenous prostacyclin and its stable analogues (e.g., iloprost) dissipated platelet thrombi as measured by a loss in the weight of the blood superfused collagen strip. This model allowed us to assay numerous drugs for their releasing properties of endogenous prostacyclin from vascular endothelium. These drugs included lipophilic angiotensin converting enzyme inhibitors (ACE-Is), which act in vivo as bradykinin potentiating factors (BPF). Other PGI₂-releasers included statins (e.g., atorvastatin and simvastatin), thienopyridines (e.g., ticlopidine and clopidogrel), a number of thromboxane synthase inhibitors, flavonoids, bradykinin itself, cholinergic M receptor agonists and nicotinic acid derivatives. The thrombolytic actions of lipophilic ACE-Is (e.g., quinapril and perindopril) were prevented by pretreatment with either bradykinin B₂ receptor antagonists (e.g., icatibant) or with endothelial COX-2 inhibitors (e.g., rofecoxib, celecoxib and high dose aspirin). The inhibition of endothelial nitric oxide synthetase (eNOS) by L-NAME hardly blunted the thrombolytic response to ACE-Is. Hence, it can be concluded that many recognized cardiovascular drugs apart from their known basic mechanisms of action, may also behave as releasers of endogenous endothelial prostacyclin. Furthermore, in many instances, this effect may be the primary mechanism of their therapeutic efficacy.     

Discovery of small molecule agonists targeting neuropeptide Y4 receptor using homology modeling and virtual screening

Neuropeptide Y4 receptor has the most significant effect on body weight and fat mass in its physiological functions, and the activation of Y4 receptor has explicit role on losing weight. The Y4 receptor has been successfully applied in the development of anti‐obesity agent, thus representing a potential therapeutic target for obesity treatment. Here, we reported the first discovery of small molecule agonists targeting Y4 receptor: three Y4 receptor models with active and inactive conformations were built, each model was submitted following structure‐based virtual screening, and finally six hits were identified as Y4 receptor agonists. These results confirm the reliability of the constructed Y4 receptor models and the proposed computational strategy for investigating novel Y4 receptor agonists. These new small molecule Y4 receptor agonists will contribute to the further development of Y4 agonists as potential therapeutics and functional probes.     

Weight-reducing side effects of the antiepileptic agents topiramate and zonisamide

Drug-induced weight alteration can be a serious side effect that applies to several therapeutic agents and must be referred to in the respective approved labeling texts. The side effect may become health threatening in case of significant weight change in either direction. Several antiepileptic drugs (AEDs) are associated with weight gain such as gabapentin, pregabalin, valproic acid, and vigabatrin and to some extent carbamazepine. Others are weight neutral such as lamotrigine, levetiracetam, and phenytoin or associated with slight weight loss as, e.g., felbamate. The focus of this chapter is on the two AEDs causing strong weight loss: topiramate and zonisamide. For both drugs, several molecular mechanisms of actions are published. We provide a review of these potential mechanisms, some of which are based on in vivo studies in animal models for obesity, and of clinical studies exploring these two drugs as single entities or in combinations with other agents.     

Prolactin-lowering and -releasing drugs. Mechanisms of action and therapeutic applications

Drugs whose systemic and/or central administration induce suppression or stimulation of prolactin secretion are reviewed. The most commonly used prolactin-lowering drugs include: (a) direct-acting dopamine receptor agonists (e.g. dopamine, apomorphine and the ergot derivatives); (b) indirect-acting dopamine agonists (e.g. amphetamine, nomifensine, methylphenidate, amineptine); (c) drugs which impair serotoninergic neurotransmission (e.g. the neurotoxin 5,7-dihydroxytryptamine and the serotonin receptor antagonists methysergide and metergoline); (d) gamma-aminobutyric acid [GABA]-mimetic drugs (e.g. GABA, muscimol, ethanolamine-O-sulphate, sodium valproate); (e) histamine H2-receptor agonists; and (f) cholinergic (muscarinic and nicotinic) receptor agonists. Major prolactin-stimulating agents comprise: (a) dopamine receptor antagonists (e.g. classic and atypical antipsychotic drugs); (b) drugs differently capable of impairing central nervous system dopamine function (e.g. blockers of dopamine neurotransmission such as alpha-methyl-p-tyrosine and 3-iodo-L-tyrosine, false precursors such as alpha-methyldopa, and inhibitors of L-aromatic amino acid decarboxylase such as carbidopa and benserazide); (c) drugs enhancing serotoninergic neurotransmission (e.g. the serotoninergic precursors tryptophan and 5-hydroxytryptophan, direct-acting serotonin agonists such as quipazine and MK 212, and indirect-acting serotonin agonists such as fenfluramine); (d) blockers of serotonin reuptake (e.g. fluoxetine, fluvoxamine and clovoxamine); (e) H1-receptor agonists; and (f) H2-receptor antagonists (e.g. cimetidine). Some of the above classes of drugs (e.g. the indirect-acting dopamine agonists, dopamine receptor antagonists, GABA-mimetic drugs, dopamine receptor blocking drugs, and H2-antagonists) may be useful for selecting among hyperprolactinaemic patients those with a prolactin-secreting tumour in an early stage of the disease. Direct-acting dopamine receptor agonists, notably the ergot derivatives; are potent antigalactopoietic agents, can revert impaired gonadal function to normal in both female and male patients with hyperprolactinaemia, and may have antiproliferative effects on pituitary prolactin-secreting tumours. All prolactin-stimulating agents, but especially the dopamine receptor antagonists, are liable to induce alterations in gonadal function in subjects of either sex. In addition to their usage for diagnostic or therapeutic purposes, the above drugs appear to be invaluable tools for enabling a better understanding of the neurotransmitter control of prolactin secretion.     

The status of pharmacotherapy for autism spectrum disorders

The use of pharmacologic agents as a component of treatment for children and adults with autism spectrum disorders is common and a substantial body of literature describing controlled and open-label clinical trials now exists to guide clinical practice. Empiric evidence of efficacy of risperidone, methylphenidate and some selective serotonin re-uptake inhibitors for maladaptive behaviors commonly associated with autism spectrum disorders has increased substantially in recent years. Preliminary controlled trials of valproate, atomoxetine, α-2 adrenergic agonists and olanzapine are promising. In addition to traditional psychotropic medications, investigators have examined the potential role of a variety of agents with glutamatergic or cholinergic mechanisms, and the results warrant further investigation. Although psychotropic medications are effective in treating some important associated behaviors, evidence of significant impact on the core features of autism spectrum disorders is very limited.     

The status of pharmacotherapy for autism spectrum disorders

The use of pharmacologic agents as a component of treatment for children and adults with autism spectrum disorders is common and a substantial body of literature describing controlled and open-label clinical trials now exists to guide clinical practice. Empiric evidence of efficacy of risperidone, methylphenidate and some selective serotonin re-uptake inhibitors for maladaptive behaviors commonly associated with autism spectrum disorders has increased substantially in recent years. Preliminary controlled trials of valproate, atomoxetine, alpha-2 adrenergic agonists and olanzapine are promising. In addition to traditional psychotropic medications, investigators have examined the potential role of a variety of agents with glutamatergic or cholinergic mechanisms, and the results warrant further investigation. Although psychotropic medications are effective in treating some important associated behaviors, evidence of significant impact on the core features of autism spectrum disorders is very limited.     

An evaluation of liraglutide including its efficacy and safety for the treatment of obesity

ABSTRACT

Introduction: The prevalence of obesity is increasing worldwide and associated conditions, particularly type 2 diabetes mellitus (T2DM), also show increasing prevalence. Lifestyle intervention should be the first line of management for obesity but additional pharmacotherapy is often required and bariatric surgery is appropriate in more severe cases. Drugs acting as glucagon-like peptide-1 receptor agonists (GLP-1RAs) developed for the management of T2DM reduce body weight and liraglutide is the first GLP-1RA to be approved for the treatment of obesity in patients with and without T2DM.

Areas covered: In this review of relevant published material, the authors summarize the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of liraglutide for the treatment of obesity.

Expert opinion: Liraglutide effectively reduces body weight and body fat through mechanisms involving reduced appetite and lowered energy intake, independent of its glucose-lowering effects. Like most of the other medications currently available for obesity, liraglutide has some common adverse effects, although generally not serious ones. Liraglutide has additional benefits in reducing cardiovascular events in patients with T2DM but the cost and the need for daily injections may limit its use in obesity. Newer GLP-1RAs, such as semaglutide, or other drugs in development for obesity may have advantages over liraglutide.