Use of somatostatin analogues in obesity.
Obesity is a condition that results from dysregulation of energy balance. Insulin, a component of the efferent pathway of the energy-regulatory circuit, promotes storage of energy substrates in adipose tissue and is, therefore, a potential target for pharmacotherapy. Somatostatin and its analogues (octreotide and lanreotide) bind to somatostatin subtype 5 receptors on the beta-cell membrane, which limits insulin release and, consequently, may decrease adipogenesis. Somatostatin and its analogues have been used in trials in patients with paediatric hypothalamic obesity. These children have hypothalamic dysfunction, mainly due to brain tumours such as craniopharyngiomas, which are thought to generate increased vagal output, leading to hyperinsulinaemia and weight gain. Two small trials, each of 6 months' duration, in children with paediatric hypothalamic obesity showed either a minimal weight loss or stabilization of bodyweight. In children with Prader-Willi syndrome, the most common genetic hypothalamic disorder associated with hyperphagia, hyperghrelinaemia, massive obesity and other endocrine disturbances, somatostatin failed to control hyperphagia and weight gain in a small number of patients, although it lowered the levels of the anorexigenic hormone ghrelin. Long-acting release octreotide was recently used in hyperinsulinaemic obese adults without cranial pathology. Insulin suppression was associated with small decreases in the body mass indexes of obese subjects receiving the higher dosages of the drug, with an acceptable safety profile, similar to that in previous studies. In conclusion, somatostatin and its analogues, by suppressing beta-cell insulin secretion, can retard weight gain in children with hypothalamic obesity and induce a small amount of weight loss in some adults with hyperinsulinaemic obesity.
Tzotzas
Themistoklis
T
Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, Greece. tzotzas@otenet.gr
Papazisis
Kostas
K
Perros
Petros
P
Krassas
Gerasimos E
GE
D000328:Adult; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications; D009765:Obesity / Q000188:drug therapy*; D011218:Prader-Willi Syndrome; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D019440:Anti-Obesity Agents; D006727:Hormone Antagonists; D013004:Somatostatin
Clin Endocrinol (Oxf). 2003 May;58(5):653-61
12699450
J Clin Endocrinol Metab. 1984 Mar;58(3):544-8
6363441
J Clin Endocrinol Metab. 2004 Nov;89(11):5435-40
15531494
Endocr Rev. 2006 Jun;27(4):371-97
16543382
Clin Ophthalmol. 2007 Sep;1(3):209-15
19668474
Diabetes. 1994 May;43(5):696-702
8168647
Curr Med Chem. 2004 Jun;11(12):1595-615
15180566
C R Biol. 2006 Aug;329(8):608-22; discussion 653-5
16860279
J Pediatr Endocrinol Metab. 2006 Feb;19(2):121-7
16562584
Horm Metab Res. 2006 Jul;38(7):442-6
16933179
J Clin Endocrinol Metab. 2004 Jul;89(7):3298-305
15240606
J Clin Endocrinol Metab. 1977 Jun;44(6):1038-53
874043
J Clin Endocrinol Metab. 2003 Jun;88(6):2586-92
12788859
J Neurosurg. 1998 Oct;89(4):547-51
9761047
Proc Soc Exp Biol Med. 1988 Dec;189(3):362-6
2905062
Intern Med. 1997 May;36(5):319-20
9213165
J Med Chem. 2003 Jun 5;46(12):2334-44
12773038
J Clin Endocrinol Metab. 2005 May;90(5):2681-90
15687345
Life Sci. 1979 Aug 13;25(7):561-6
388132
Clin Endocrinol (Oxf). 2003 Oct;59(4):492-9
14510913
Int J Obes Relat Metab Disord. 2004 Feb;28(2):330-3
14708034
Eur J Endocrinol. 1994 Jun;130(6):581-6
8205258
Drugs. 1997 Apr;53(4):681-99
9098666
Best Pract Res Clin Gastroenterol. 2002 Jun;16(3):493-509
12079271
Int J Obes (Lond). 2006 Feb;30(2):331-41
16158082
Curr Med Chem. 2001 Nov;8(13):1605-48
11562281
Obes Surg. 1993 May;3(2):197-200
10757921
Obes Res. 1995 Nov;3 Suppl 4:591S-603S
8697062
J Pediatr. 1999 Aug;135(2 Pt 1):162-8
10431109
Mol Endocrinol. 2003 Jan;17(1):93-106
12511609
Clin Endocrinol (Oxf). 2002 Oct;57(4):539-46
12354137
Horm Res. 1998;49(1):17-21
9438780
J Clin Endocrinol Metab. 2003 Aug;88(8):3573-6
12915638
Int J Obes (Lond). 2006 Feb;30(2):382-7
16231029
Recent Prog Horm Res. 1998;53:95-117; discussion 117-8
9769705
Arch Intern Med. 1991 Aug;151(8):1573-8
1872661
J Comp Physiol Psychol. 1981 Apr;95(2):278-87
6112246
Baillieres Best Pract Res Clin Endocrinol Metab. 1999 Oct;13(3):409-18
10909432
J Clin Endocrinol Metab. 2007 Nov;92(11):4101-6
17726084
Metabolism. 1992 Sep;41(9 Suppl 2):76-9
1518438
Int J Obes (Lond). 2006 Feb;30(2):313-21
16276365
Science. 2005 Mar 25;307(5717):1909-14
15790843
J Clin Endocrinol Metab. 2005 Jul;90(7):3854-62
15827099
Science. 1973 Jan 5;179(4068):77-9
4682131
Acta Endocrinol Suppl (Copenh). 1987;286:19-25
2892334
Nutr Metab Cardiovasc Dis. 2008 Feb;18(2):158-68
18061414
Diabetes. 1997 Jun;46(6):1025-9
9166675
Obes Res. 2005 Sep;13(9):1572-9
16222060
Pharmacol Biochem Behav. 1982 Jun;16(6):897-902
6125953
Endocr Rev. 1995 Aug;16(4):427-42
8521788
Int J Obes Relat Metab Disord. 2003 Feb;27(2):219-26
12587002
Medicine (Baltimore). 1975 Jul;54(4):301-30
1152672
Neurosci Biobehav Rev. 1982 Summer;6(2):205-14
7048155
Int J Obes Relat Metab Disord. 2003 Aug;27(8):875-88
12861227
Nat Med. 2002 Jul;8(7):643-4
12091883
Int J Obes Relat Metab Disord. 1993 Sep;17(9):527-32
8220655
Obesity (Silver Spring). 2006 Jun;14(6):1028-37
16861608
N Engl J Med. 1996 Jan 25;334(4):246-54
8532003
Clin Chim Acta. 2007 Jan;375(1-2):20-35
16956601
J Biol Chem. 1991 Jan 15;266(2):837-43
1702440
J Pediatr. 2005 Apr;146(4):474-81
15812449
J Clin Endocrinol Metab. 2004 Aug;89(8):4162-5
15292365
Expert Opin Investig Drugs. 2006 Aug;15(8):897-915
16859393
J Clin Endocrinol Metab. 2006 May;91(5):1811-8
16507637
Obes Rev. 2002 Feb;3(1):27-34
12119657
Front Neuroendocrinol. 2003 Jan;24(1):1-10
12609497
Trends Genet. 1998 May;14(5):194-200
9613204
Lancet. 1983 Jun 11;1(8337):1330-1
6134114
Nutr Rev. 1998 Apr;56(4 Pt 1):106-14
9584495
Gut. 2003 Nov;52(11):1555-61
14570722
Endocrinology. 2000 Jan;141(1):111-7
10614629
J Clin Endocrinol Metab. 2003 May;88(5):2180-4
12727973
Diabetologia. 1985 Feb;28(2):70-5
3884419
Prog Brain Res. 2006;153:57-73
16876568
Eur J Endocrinol. 2005 Jun;152(6):887-94
15941929
Fertil Steril. 2006 Jul;86 Suppl 1:S28-9
16798283
Pediatr Endocrinol Rev. 2004 Aug;1 Suppl 3:448-54
16444173
J Pediatr. 2006 Jan;148(1):23-9
16423593
J Clin Endocrinol Metab. 2001 Sep;86(9):4330-8
11549670
J Endocrinol Invest. 1997 Jun;20(6):348-67
9294784