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448 Obesity- Pharmacotherapy

GSK1521498 effects compared with centrally acting drugs. Given
the high unmet need and our growing understanding
GSK1521498 is a µ-opioid receptor inverse agonist that of the complexity of pathogenesis of obesity, novel,
is being investigated for the treatment of overeating more efficacious and better tolerated treatments for
behavior in obesity, it have been shown to reduce obesity are clearly required
short-term food intake and affective or subjective
pleasantness of palatable foods in healthy participants References
A study in healthy volunteers showed that GSK1521498 1. Prospective Studies Collaboration. Lancet 2009; 373:1083–1096.
seletively reduced food craving for high-sugar and
high fat dairy products and caloric intake of high- 2. WHO Obesity and overweight www.who.int/mediacentre/factsheets/fs311/
fat snack foods. phase 1 study showed the drug to en/index.html
have an acceptable safety profile when the drug was 3. Richard D. Cognitive and autonomic determinants of energy homeostasis
administered for 10 days in multiple doses. It remains in obesity. Nat Rev Endocrinal 2015; 11: 489–501.
to be seen whether the decreased food craving would 4. Public Citizen Comments on FDA Obesity Trial Guidelines www.citizen.
translate into significant weight reduction when the org/page.aspx?pid=742
drug is given for long period. 5. European Medicines Agency. Committee for Medicinal Products for Human
Use. Guideline on clinical evaluation of medicinal products used in weight
Table 3. Anti obesity drugs in pipeline control (CPMP/EWP/281/96 Rev. 1). London, UK, 15 November 2007.
Doc. Ref. EMEA/CHMP/EWP/517497/2007 (2007).
AgRP, agouti-related protein;, GLP-1, glucagon-like
peptide 1; GCGR, glucagon receptor; MetAP2, methi- 6. Smith SR, Weissman NJ, Anderson CM et al.; Behavioral modification
and lorcaserin for over- weight and obesity management (BLOOM) Study
onine aminopeptidase 2; MTP, microsomal triglycer- Group. Multicenter, placebo-controlled trial of lorcaserin for weight
ide transfer protein; management. N Engl J Med 2010; 363: 245–56.

Drug Mechanism of Action Clinical Development Phase
Velneperit Neuropeptide Y5 receptor antagonist Phase 2 completed

Tesofensine Triple monoamine reuptake inhibitor Phase 3 initiated
JNJ-16269110 MTP inhibitor Phase 2 completed
Beloranib MetAP-2 inhibitor Phase 2 completed
TTP-435 AgRP Inhibitors Phase 2 completed
Oxyntomodulin DualGLP1R and GCGR agonist Phase 2 ongoing

PF-04971729 Phase 1 completed
Selective inhibitor of the sodium-
dependent glucose cotransporter 2

GSK1521498 -Opioid inverse agonist Phase 1 completed

Conclusions 7. Weissman NJ, Sanchez M, Koch GG, Smith SR, Shanahan WR, Anderson
CM. Echocardiographic assessment of cardiac valvular regurgitation with
Obesity has changed from being a rare, and perhaps lorcaserin from analysis of 3 phase 3 clinical trials. Circ Cardiovasc Imaging
even revered, occurrence to a condition that is 2013; 6: 560–7.
common in a large proportion of the population in the 8. Fidler MC, Sanchez M, Raether B et al. ; BLOS- SOM Clinical Trial Group.
developed world. Pharmacotherapy even with all the A one-year random- ized trial of lorcaserin for weight loss in obese and
limitations plays an important role in the treatment overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 2011;
of obesity, by modestly improving the weight loss 96: 3067–77.
obtained with diet and exercise and thus helps in
reducing the impact of comorbidities associated with
obesity. . Recent advances in the understanding of
energy balance control have highlighted a number
potential novel targets for therapeutic intervention. Gut
hormones may be especially promising candidates
for future exploration due to relatively few side

GCDC 2017