Table 1: Leptin-sensitizing gut hormones.

Satiety-signaling gut hormones combined with leptin therapy can induce greater effects on weight loss than either hormone alone in rodent models. Exogenous administration of these hormones with leptin can re-sensitize leptin resistant animals to leptin signaling. The therapeutic potential of these hormones in combination with leptin is highlighted by the current production and use of analogues to many of these hormones in clinical practice. GLP-1, Glugagon-Like Peptide 1; IL-6, Interleukin 6; LepR, Leptin Receptor; ICV, Intracerebroventricular.

Hormone	Hormone Analogue	Efficacy with Leptin	References
Amylin (pancreatic B cells)	Pramlintide (Symlin, Astrazeneca)	Synergistic weight loss effect with leptin, mediated by IL-6 in the Ventromedial Hypothalamus, also enhances GLP-1 weight loss	[150–152]
GLP-1 (intestinal L-cells)	Exendin-4/Exenatide (Byetta, Astrazeneca)	Restores leptin sensitivity, along with glucagon receptor agonist greatly enhances weight loss over leptin alone, also enhances Amylin weight loss	[157,158]
Uroguanylin (intestinal epithelium)	Plecanatide (Trulance, Salix), Linaclotide (Linzess, Allergan & Ironwood)	Re-sensitizes obese mice to leptin, synergistic effect with central co-administration with leptin, induces thermogenesis in brown adipose tissue	[160,161,163]
Cholecystokinin (Intestinal I-cells)	Sincalide (Kinevac, Bracco Diagnostics)	Synergistic effect with low-dose ICV leptin, only peripheral Cholecystokinin coupled with ICV leptin was effective	[167,168]
Peptide YY (Intestinal L-cells)	N/A	Leptin therapy coupled with Peptide YY increased weight loss over either alone, and extended anorectic effect of Peptide YY	[169]