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Expert Opinion on Biological Therapy Volume 8, 2008 - Issue 11
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Reviews

Hormone-based therapies in the regulation of fuel metabolism and body weight

Nicole C Kesty Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA 92121, USA +1 858 458 8616; +1 858 824 7605; [email protected]
, PhD,
Jonathan D Roth Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA 92121, USA +1 858 458 8616; +1 858 824 7605; [email protected]
, PhD &
David Maggs Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, San Diego, CA 92121, USA +1 858 458 8616; +1 858 824 7605; [email protected]
, MD
Pages 1733-1747 | Published online: 10 Oct 2008

Bibliography

  • World Health Organization. Country and regional data. Available from: http://www.who.int/diabetes/facts/world_figures/en/ [Accessed 2008 Feb 22]
  • World Health Organization. Fact sheet N 311 Obesity and overweight. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/. 2006 [Last accessed 2008 Feb 22]
  • Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006;295:1549-55
  • Pinhas-Hamiel O, Zeitler P. Clinical presentation and treatment of type 2 diabetes in children. Pediatr Diabetes 2007;8:16-27
  • Pi-Sunyer FX. The medical risks of obesity. Obes Surg 2002;12(Suppl 1):S6-S11
  • Young AA. Amylin's physiology and its role in diabetes. Curr Opin Endocrinol Diab 1997;4:282-90
  • Nielsen LL, Young AA, Parkes DG. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept 2004;117:77-88
  • Yip RG, Wolfe MM. GIP biology and fat metabolism. Life Sci 2000;66:91-103
  • Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717-23
  • Stonehouse AH, Maggs DG. Emerging therapies for type 2 diabetes. Curr Drug Therapy 2007;2:151-60
  • Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879-84
  • Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002;110:1093-103
  • Wynne K, Stanley S, McGowan B, et al. Appetite control. J Endocrinol 2005;184:291-318
  • Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med 2005;143:380-5
  • UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-65
  • Purnell J, Weyer C. Weight effect of current and experimental drugs for diabetes mellitus: from promotion to alleviation of obesity. Treat Endocrinol 2003;2:33-47
  • Seeley RJ, Woods SC. Monitoring of stored and available fuel by the CNS: implications for obesity. Nat Rev Neurosci 2003;4:901-9
  • Air EL, Benoit SC, Clegg DJ, et al. Insulin and leptin combine additively to reduce food intake and body weight in rats. Endocrinology 2002;143:2449-52
  • Hallschmid M, Benedict C, Schultes B, et al. Intranasal insulin reduces body fat in men but not in women. Diabetes 2004;53:3024-9
  • Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 2003;284:E671-8
  • Petersen KF, Sullivan JT. Effects of a novel glucagon receptor antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans. Diabetologia 2001;44:2018-24
  • Makimattila S, Fineman MS, Yki-Jarvinen H. Deficiency of total and nonglycosylated amylin in plasma characterizes subjects with impaired glucose tolerance and type 2 diabetes. J Clin Endocrinol Metab 2000;85:2822-7
  • Kruger DF, Gloster MA. Pramlintide for the treatment of insulin-requiring diabetes mellitus: rationale and review of clinical data. Drugs 2004;64:1419-32
  • Chapman I, Parker B, Doran S, et al. Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes. Diabetologia 2005;48:838-48
  • Ratner RE, Want LL, Fineman MS, et al. Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes. Diabetes Technol Ther 2002;4:51-61
  • Ratner RE, Dickey R, Fineman M, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year randomized controlled trial. Diabet Med 2004;21:1204-12
  • Whitehouse F, Kruger DF, Fineman M, et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care 2002;25:724-30
  • Hollander PA, Levy P, Fineman MS, et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 2003;26:784-90
  • Karl D, Philis-Tsimikas A, Darsow T, et al. Pramlintide as an adjunct to insulin in patients with type 2 diabetes in a clinical practice setting reduced A1C, postprandial glucose excursions and weight. Diabetes Technol Ther 2007;9:191-9
  • Guthrie R, Karl D, Wang Y, et al. I n an open-label clinical study pramlintide lowered A1C, body weight, and insulin use in patients with type 1 diabetes failing to achieve glycemic targets with insulin therapy [abstract 478-P]. Diabetes 2005;54(Suppl 1):A118
  • Roth JD, Hughes H, Kendall E, et al. Anti-obesity effects of the β-cell hormone amylin in diet induced obese rats: effects on food intake, body weight, composition, energy expenditure and gene expression. Endocrinology 2006;147:5855-64
  • Mack CM, Wilson J, Athanacio J, et al. Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference and body weight. Am J Physiol Regul Integr Comp Physiol 2007;293:R1855-63
  • Smith SR, Blundell JE, Burns C, et al. Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study. Am J Physiol Endocrinol Metab 2007;293:E620-7
  • Aronne L, Fujioka K, Aroda V, et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab 2007;92:2977-83
  • Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12 months pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care 2008;31:1816-23
  • Huda MS, Wilding JP, Pinkney JH. Gut peptides and the regulation of appetite. Obes Rev 2006;7:163-82
  • Berntson GG, Zipf WB, O'Dorisio TM, et al. Pancreatic polypeptide infusions reduce food intake in Prader-Willi syndrome. Peptides 1993;14:497-503
  • Batterham RL, Le Roux CW, Cohen MA, et al. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 2003;88:3989-92
  • Lassmann V, Vague P, Vialettes B, et al. Low plasma levels of pancreatic polypeptide in obesity. Diabetes 1980;29:428-30
  • Jorde R, Burhol PG. Effects of synthetic porcine GIP on the PP release in healthy subjects. Acta Physiol Scand 1984;121:143-6
  • Glaser B, Shapiro B, Glowniak J, et al. Effects of secretin on the normal and pathological beta-cell. J Clin Endocrinol Metab 1988;66:1138-43
  • Gibbs J, Young RC, Smith GP. Cholecystokinin elicits satiety in rats with open gastric fistulas. Nature 1973;245:323-5
  • West DB, Fey D, Woods SC. Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 1984;246:R776-87
  • Crawley JN, Beinfeld MC. Rapid development of tolerance to the behavioural actions of cholecystokinin. Nature 1983;302:703-6
  • Jordan J, Greenway FL, Leiter LA, et al. Stimulation of cholecystokinin-A receptors with GI181771X does not cause weight loss in overweight or obese patients. Clin Pharmacol Ther 2008;83:281-7
  • Dakin CL, Small CJ, Batterham RL, et al. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 2004;145: 2687-95
  • Cohen MA, Ellis SM, Le Roux CW, et al. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab 2003;88:4696-701
  • Wynne K, Park AJ, Small CJ, et al. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J Obes 2006;30:1729-36
  • Wynne K, Park AJ, Small CJ, et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes 2005;54:2390-5
  • Brubaker PL, Anini Y. Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol 2003;81:1005-12
  • Lupi R, Mancarella R, Del Guerra S, et al. Effects of exendin-4 on islets from type 2 diabetes patients. Diabetes Obes Metab 2008;10(6):515-9
  • Buse JB, Henry RR, Han J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628-35
  • DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092-100
  • Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083-91
  • Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008;24:275-86
  • Zinman B, Hoogwerf BJ, Duran Garcia S, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2007;146:477-85
  • Stonehouse AH, Holcombe JH, Kendall DM. Management of type 2 diabetes: the role of incretin mimetics. Exp Opin Pharmacother 2006;7:2095-105
  • Nauck MA, Hompesch M, Filipczak R, et al. Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes. Exp Clin Endocrinol Diabetes 2006;114:417-23
  • Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993;91:301-7
  • Marre M, Shaw J, Brandle M, et al. Liraglutide, a once-daily human GLP-1 analog, added to a sulfonylurea (SU) offers significantly better glycemic control and favorable weight change compared to rosiglitazone and SU combination therapy in subjects with type 2 diabetes [abstract 13-OR]. Diabetes 2008;57:A4
  • Russell-Jones D, Vaag A, Schmitz O, et al. Significantly better glycemic control and weight reduction with liraglutide, a once-daily human GLP-1 analog, compared with insulin glargine: all as add-on to metformin and a sulfonylurea in type 2 diabetes [abstract 536-P]. Diabetes 2008;57:A159-60
  • Baggio LL, Huang Q, Cao X, et al. An albumin-exendin-4 conjugate engages central and peripheral circuits regulating murine energy and glucose homeostasis. Gastroenterology 2008;134(4):1137-47
  • Wang M, Kipnes M, Matheson S, et al. Safety and pharmacodynamics of CJC-1134-PC, a novel glp-1 receptor agonist, in patients with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blind, dose-escalation study [abstract 498-P]. Diabetes 2007;56(Suppl 1):A133
  • Drucker D, Buse J, Taylor K, et al. Exenatide once weekly results in significantly greater improvements in glycemic control compared to exenatide twice daily in patients with type 2 diabetes [abstract 107-OR]. Diabetes 2008;57:A33
  • Rosenstock J, Zinman B. Dipeptidyl peptidase-4 inhibitors and the management of type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 2007;14:98-107
  • Aschner P, Lunceford J, Williams-Herman D. Once-daily sitagliptin monotherapy provides effective glycemic control over 54 weeks and is well tolerated in patients with type 2 diabetes [abstract 2181-PO]. Diabetes 2007;56(Suppl 1):A553
  • Hermansen K, Kipnes M, Luo E, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab 2007;9:733-45
  • Goldstein B, Feinglos M, Lunceford J, et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care 2007;30:1979-87
  • Hermansen K, Kipnes M, Luo E, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab 2007;9:733-45
  • Scherbaum WA, Schweizer A, Mari A, et al. Efficacy and tolerability of vildagliptin in drug-naive patients with type 2 diabetes and mild hyperglycaemia. Diabetes Obes Metab 2008;10:675-82
  • Scrocchi LA, Brown TJ, MaClusky N, et al. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 1996;2:1254-8
  • Mack CM, Moore CX, Jodka CM, et al. Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures. Int J Obes (Lond) 2006;30:1332-40
  • Young AA, Gedulin BR, Bhavsar S, et al. Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic Fatty Zucker rats and diabetic rhesus monkeys (Macaca mulatta). Diabetes 1999;48:1026-34
  • Gutzwiller JP, Göke B, Drewe J, et al. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 1999;44:81-6
  • Flint A, Raben A, Astrup A, et al. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998;101:515-20
  • Naslund E, Barkeling B, King N, et al. Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 1999;23:304-11
  • Verdich C, Flint A, Gutzwiller JP, et al. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 2001;86:4382-9
  • Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696-705
  • Unniappan S, McIntosh CH, Demuth HU, et al. Effects of dipeptidyl peptidase IV on the satiety actions of peptide YY. Diabetologia 2006;49:1915-23
  • Edwards CM, Stanley SA, Davis R, et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001;281:E155-61
  • Woods SC, West DB, Stein LJ, et al. Peptides and the control of meal size. Diabetologia 1981;20:305-13
  • Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 2002;8:738-42
  • Winter KD, Ehses JA, Eeson G, et al. Effects of glucose-dependent insulinotropic polypeptide on the phosphorylation of protein kinase B (PKB/AKT) and its contribution to pancreatic beta-cell survival. J Investig Med 2007;55:S124
  • Holst JJ. Gastric inhibitory polypeptide analogues: do they have a therapeutic role in diabetes mellitus similar to that of glucagon-like Peptide-1? BioDrugs 2002;16:175-81
  • Gedulin B, Hargrove D, Smith P, et al. Novel long acting GIP analogs with potent insulinotropic and gastric emptying effects in rodents [abstract 1483-P]. Diabetes 2008;57:A416-7
  • Druce MR, Small CJ, Bloom SR. Minireview: Gut peptides regulating satiety. Endocrinology 2004;145:2660-5
  • Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001;86:5992
  • Cummings DE, Purnell JQ, Frayo RS, et al. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001;50:1714-9
  • Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346:1623-30
  • Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 2007;8:21-34
  • Tschop M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001;50:707-9
  • Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 2003;23:7973-81
  • Sun Y, Wang P, Zheng H, et al. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci USA 2004;101:4679-84
  • Wortley KE, Anderson KD, Garcia K, et al. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci USA 2004;101:8227-32
  • Asakawa A, Inui A, Kaga T, et al. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 2003;52:947-52
  • Bagnasco M, Tulipano G, Melis MR, et al. Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting. Regul Pept 2003;111:161-7
  • Shuto Y, Shibasaki T, Otagiri A, et al. Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity. J Clin Invest 2002;109:1429-36
  • Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001;409:194-8
  • Adrian TE, Ferri GL, Bacarese-Hamilton AJ, et al. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985;89:1070-7
  • Grandt D, Schimiczek M, Beglinger C, et al. Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept 1994;51:151-9
  • Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003;349:941-8
  • le Roux CW, Batterham RL, Aylwin SJ, et al. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 2006;147:3-8
  • Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002;418:650-4
  • Pittner RA, Moore CX, Bhavsar SP, et al. Effects of PYY[3-36] in rodent models of diabetes and obesity. Int J Obes Relat Metab Disord 2004;28:963-71
  • Bhavsar S, Hoyt J, Paterniti JR, et al. Continuous infusion of PYY[3-36] reduces food consumption and body weight in Fatty Zucker (fa/fa) rats [abstract 2499-PO]. Diabetes 2002;51:A602
  • Bhavsar S, Parkes D, Hoyt J, et al. PYY[3-36] decreases food consumption and improves glycemic control in Zucker Diabetes Fatty (ZDF) rats [abstract 1717-P]. Diabetes 2002;51:A418-9
  • Challis BG, Pinnock SB, Coll AP, et al. Acute effects of PYY(3-36) on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Commun 2003;311:915-9
  • Tschop M, Castaneda TR, Joost HG, et al. Physiology: does gut hormone PYY3-36 decrease food intake in rodents? Nature 2004;430, Available from: http://www.nature.com/nature/journa/v430/n6996/full/nature02665.html [Last accessed June 2007]
  • Koegler FH, Enriori PJ, Billes SK, et al. Peptide YY(3-36) inhibits morning, but not evening, food intake and decreases body weight in rhesus macaques. Diabetes 2005;54:3198-204
  • Lush C, Chen K, Hompesch M, et al. A phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of rising doses of AC162352 (synthetic human PYY3-36) in lean and obese subjects [abstract O051]. Obes Rev 2005;6:21
  • Degen L, Oesch S, Casanova M, et al. Effect of peptide YY3-36 on food intake in humans. Gastroenterology 2005;129:1430-6
  • Gantz I, Erondu N, Mallick M, et al. Efficacy and safety of intranasal peptide YY3-36 for weight reduction in obese adults. J Clin Endocrinol Metab 2007;92:1754-7
  • Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 1996;97:1344-7
  • Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-32
  • Halaas JL, Gajiwala KS, Maffei M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-6
  • Campfield LA, Smith FJ, Guisez Y, et al. Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546-9
  • Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-3
  • Chehab FE, Lim ME, Lu RH. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996;12:318-20
  • Van Heek M, Compton DS, France CF, et al. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest 1997;99:385-90
  • Licinio J, Caglayan S, Ozata M, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci USA 2004;101:4531-6
  • Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002;346:570-8
  • Javor ED, Cochran EK, Musso C, et al. Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes 2005;54:1994-2002
  • Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999;282:1568-75
  • Hukshorn CJ, Saris WH, Westerterp-Plantenga MS, et al. Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J Clin Endocrinol Metab 2000;85:4003-9
  • Shklyaev S, Aslanidi G, Tennant M, et al. Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats. Proc Natl Acad Sci USA 2003;100:14217-22
  • Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001;98:2005-10
  • American Diabetes Association. Standards of Medical Care in Diabetes-2008. Diabetes Care 2008;31(Suppl 1):S12-54
  • Rosenbaum M, Goldsmith R, Bloomfield D, et al. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest 2005;115:3579-86
  • Rosenbaum M, Murphy EM, Heymsfield SB, et al. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002;87:2391-4
  • Matson CA, Reid DF, Cannon TA, et al. Cholecystokinin and leptin act synergistically to reduce body weight. Am J Physiol Regul Integr Comp Physiol 2000;278:R882-90
  • Bhavsar S, Watkins J, Young A. Synergy between amylin and cholecystokinin for inhibition of food intake in mice. Physiol Behav 1998;64:557-61
  • Barrachina MD, Martinez V, Wang L, et al. Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice. Proc Natl Acad Sci USA 1997;94:10455-60
  • Riedy CA, Chavez M, Figlewicz DP, et al. Central insulin enhances sensitivity to cholecystokinin. Physiol Behav 1995;58:755-60
  • Neary NM, Small CJ, Druce MR, et al. Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively. Endocrinology 2005;146:5120-7
  • Talsania T, Anini Y, Siu S, et al. Peripheral exendin-4 and peptide YY3-36 synergistically reduce food intake through different mechanisms in mice. Endocrinology 2005;146:3748-56
  • Gutzwiller JP, Degen L, Matzinger D, et al. Interaction between GLP-1 and CCK33 in inhibiting food intake and appetite in men. Am J Physiol Regul Integr Comp Physiol 2004;287:R562-7
  • Roth J, Barnhill S, Lei C, et al. Multihormonal treatment with amylin, PYY (3-36), and leptin elicited marked, fat-specific weight loss in diet-induced obese (DIO) rats [abstract 177-P]. Obesity 2006;14(Suppl):A57-8
  • Roth JD, Coffey T, Jodka C, et al. Combination therapy with amylin and PYY(3-36) in obese rodents: Anorexigenic synergy and weight loss additivity. Endocrinology 2007;148:6054-61
  • Roth J, Weyer C, Anderson C, et al. Leptin responsivity restored in leptin-resistant diet-induced obese (DIO) rats: synergistic actions of amylin and leptin for reduction in body weight (BW) and fat [abstract 52-LB]. American Diabetes Association 66th Scientific Sessions. Washington, DC; 2006
  • Roth JD, Roland B, Cole R, et al. Responsiveness to leptin restored by amylin in diet induced obese (DIO) rats: magnitude and mechanisms of synergy [abstract 277-OR]. Diabetes 2007;56(Suppl 1):A72
  • Roth JD, Roland B, Cole R, et al. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 2008;105:7257-62
  • Trevaskis JL, Wittmer C, Coffey T, et al. Amylin plus leptin combination therapy in diet-induced obese (DIO) rats: mechanisms additional to inhibition of food intake [abstract 189-P]. Obesity 2007;15:A60-1
  • Finkelstein EA, Fiebelkorn IC, Wang G. National medical spending attributable to overweight and obesity: how much, and who's paying? Health Aff (Millwood) 2003;(Suppl Web Exclusives):W3-219-226
  • American Diabetes Association. Economic costs of diabetes in the U.S. in 2007. Diabetes Care 2008;31:1-20

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