SummaryObjective To evaluate the efficacy, safety and tolerability of octreotide LAR ® (long-acting repeatable octreotide) in the primary therapy of acromegaly. Design and patients Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10 -30 mg every 4 weeks, and constituted the population used for this analysis.Measurements and results A clinically relevant reduction (i.e. to ≤ 5 µ g/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a 'safe' GH value ( ≤ 2·5 µ g/l). At week 48, 16 more patients were considered partial GH responders (GH > 2·5 µ g/l and ≤ 5 µ g/l) and 44% had reached a GH level ≤ 2·5 µ g/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14·7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 ± 145 mm 3 to 139 ± 94 mm 3 after 24 weeks and to 99 ± 70 mm 3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 ± 5077 mm 3 at baseline and 2723 ± 3435 and 2406 ± 3207 mm 3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant ( > 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period. Conclusion Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.
Single-dose pharmacokinetic (PK) profiles and multiple-dose PK modeling were compared for long-acting octreotide (20 or 60 mg) and prolonged-release lanreotide (90 or 120 mg) over 91 days; steady-state profiles were simulated. All treatments were well tolerated. Octreotide 20-mg profile showed increased concentration on day 1, lag from days 2 to 6, then prolonged plateau phase (days 11-41); 60-mg PK was dose proportional. Lanreotide 90-mg profile showed C(max) on day 1 then elimination (apparent t1/2 25.5 days); 120-mg profile was underproportional. Steady-state PK of octreotide 20 mg/28 d suggested a C(mean) of 1216 rhog/mL (range, 1065-1585) with low fluctuation index (43%). Steady-state PK of lanreotide 90 mg/28 d suggested a C(mean) of 4455 rhog/mL (range, 2499-9279) with high fluctuation index (152%). Long-acting octreotide had more predictable PK than prolonged-release lanreotide. Simulated steady-state profiles suggest long-acting octreotide could be optimized to meet individual patient needs. In contrast, prolonged-release lanreotide requires exposure constantly above the therapeutic target to enable monthly long-term therapy.
This first randomized study in unselected patients indicates that the 48-week treatment outcome of octreotide LAR as first-line treatment of acromegaly does not significantly differ from surgery. As a complete response to surgery in GH-secreting macro-adenomas can be difficult, first-line therapy with octreotide LAR can be considered as a viable alternative for most patients with acromegaly, due to its low complication rate.
This study aimed to investigate whether a community-based participatory diabetes care program could efficiently improve diabetic care and reduce its risk factors. To induce a participatory approach, a local group was established in partnership with academics, local leaders, health providers and public representatives. The group conducted community needs assessment and priority setting process. Diabetes was identified as the first priority health problem in this area. A total of 2569 30- to 65-year-old residents were screened for diabetes and 405 of them took part in a 13-week nutrition education and physical exercise intervention. Out of 1336 high-risk individuals, 17% had fasting blood sugar (FBS) ≥126 mg/dl and 13.5% with FBS between 110 and 125 mg/dl. Percentages of participants with triglycerides (TG) ≥150 mg/dl and cholesterol ≥200 mg/dl were 33.8% and 23.5%, respectively. After completion of the intervention, the mean FBS, HbA1C, TG and cholesterol were decreased significantly. Although systolic and diastolic blood pressure and body mass index were decreased too, the differences were not statistically significant. The mean physical activity increased and consumption of fried foods and saturated oil decreased significantly. The results suggest that participatory community-based care could be a feasible model for control of diabetes and its risk factors.
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