The effect of a new slow-release, long-acting somatostatin analogue, lanreotide, in acromegaly.
OBJECTIVE
Previous studies have shown that somatostatin analogues such as octreotide and lanreotide are effective in suppressing GH and IGF-I levels in acromegaly, but the mode of administration and the frequency of injections were inconvenient for the patients. We have evaluated the effects of a new slow-release (SR), long-acting formulation of lanreotide, a somatostatin analogue, on clinical, biochemical and safety responses in acromegaly.


METHODS
We studied the effects of SR-lanreotide 30 mg administered intramuscularly twice or three times monthly for 6 months. Ten patients were studied, in whom acromegaly was confirmed by clinical features,mean GH > 5 mU/l, and failure to suppress GH to < 2 mU/l after a 75-g oral glucose load.


METHODS
Subjective improvement in clinical symptoms of acromegaly was graded and recorded. Any adverse reactions were noted. Plasma GH levels were measured every 10 min for one hour from 08300930h; fasting IGF-I levels were determined at 0830h; GH, glucose and insulin responses to oral glucose loading were measured at 0,30,60,90 and 120 minutes from 0930 to 1130h. Baseline measurements were carried out and repeated at 3 and 6 months. Biliary ultrasonography was performed at baseline and 6 months.


RESULTS
GH levels in the 10 patients decreased from 26.8 12.0 (mean SEM) to 12.7 7.0 mU/l at 3 months (P = 0.04) and 9.8 5.0 mU/l at 6 months (P = 0.06). Fasting IGF-I levels decreased from 123.2 27.0 to 73.5 13.0 nmol/l at 3 months (P = 0.01), and increased slightly to 97.4 31.0 nmol/l (P = 0.05) but remained below baseline levels at 6 months. Five patients achieved good control (GH < 5 mU/l) at 3 months. In the remaining 5 patients the dose frequency was increased to every 10 days and one achieved good control. IGF-I levels normalized in 3 and 5 patients at 3 and 6 months, respectively. Fasting insulin levels and peak insulin after an oral glucose load did not change significantly at 3 months but decreased from 11.7 2.0 to 7.8 3.3 mU/l (P = 0.05) and 106.2 24.6 to 53.3 14.3 mU/l (P = 0.04) at 6 months, respectively. There was no significant change in fasting glucose at 3 or 6 months. Most patients reported clinical improvement in acromegalic symptoms. No major adverse events were reported, but mild to moderate gastrointestinal symptoms were recorded after the initial injections. One patient developed asymptomatic gallstones at 6 months.


CONCLUSIONS
This slow-release formulation of lanreotide given either twice or thrice monthly was well tolerated, more convenient for patients, effective in controlling and alleviating the symptoms of acromegaly, as well as suppressing GH and IGF-I levels, and had no detrimental effects on carbohydrate tolerance in acromegaly.
al-Maskari
M
M
Department of medicine, University of Newcastle Upon Tyne, UK.
Gebbie
J
J
Kendall-Taylor
P
P
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007273:Injections, Intramuscular; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D007328:Insulin; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone