Search

Patients with acromegaly, who are not cured after transsphenoidal adenomectomy, may be treated with external irradiation and/or octreotide injections. Recently, a long-acting formulation of octreotide (Sandostatin LAR®) has become available in clinical practice. We assessed the effects of treatment with this long-acting octreotide in 18 consecutive patients with acromegaly treated in our center, who had persistent signs and symptoms of acromegaly despite transsphenoidal surgery with (n=7) or without irradiation (n=11). Twelve had already been treated with regular Sandostatin for a period of 0.5–8 years in dosages of 3×50 to 3×300 mcg s.c. (median daily dose 300 mcg). All patients started with i.m. injections of 20 mg Sandostatin LAR®every 4 weeks. In the patients who started treatment with octreotide for the first time, mean serum IGF-1 levels (measured by IRMA, Nichols Diagnostics) decreased from 634±229 to 255±88 ng/ml after 3 months, 271±81 ng/ml after 1 year and 263±97 ng/ml after 2 years (all P<0.05), while random GH levels (DELFIA, Wallac) decreased from 6.6 (range 3.1–67.0) to 2.1 (0.5–3.1) mU/l after 2 years (P<0.05). In the 12 patients who had already been treated with octreotide, mean IGF-1 also fell, from 367±193 to 331±195 ng/ml (P=0.023) after 3 months, to 342±191 ng/ml after 1 year and 277±169 ng/ml (P=0.002) after 2 years, while random GH levels decreased from 4.5 (1.1–46) mU/l at baseline to 2.1 (0.4–23.0) after 2 years (P=0.003). Therefore, the average decrease of IGF-1 was 10% after 3 months and 25% after 2 years. One patient had a decrease of less than 5% (but her IGF-1 was normal, 193 ng/ml), and one patient showed no response to both regular and long-acting Sandostatin (ave. IGF-1, 755 ng/ml). No specific side-effects occurred. One patient chose to return to t.i.d. injection of regular octreotide because of slight worsening of her complaints of headache despite normal IGF-1 levels. All other patients favoured continuation of the monthly injections. In six patients, the dose had to be increased to 30–40 mg monthly because the IGF-1 levels still remained elevated. Sandostatin LAR®may be considered a great improvement for the treatment of patients with (symptomatic) acromegaly.

Type 2 diabetes mellitus is characterised by impaired insulin secretion, diminished peripheral insulin action and increased hepatic glucose production. Clinical trials have indicated that near-normal glucose control may reduce the risk for microvascular and - to a lesser extent - macrovascular complications in Type 2 diabetic patients. Thiazolidinediones improve insulin action by activating a nuclear receptor, PPARγ. Therefore, these drugs are often referred to as ‘insulin sensitisers’. Rosiglitazone is the second compound of this group. Clinical studies with rosiglitazone have shown that it is effective in lowering blood glucose levels in Type 2 diabetic patients treated with either diet alone, sulphonylurea or metformin. Preliminary studies suggest that rosiglitazone also improves glycaemic control in insulin-treated patients while even slightly decreasing insulin dose. The magnitude of the effects is, however, moderate. In diet-treated patients, the reduction of HbA1c levels amounted on average 0.5 - 1.5% and addition to existing sulphonylurea therapy decreased HbA1c by 1.0 - 1.2%. The clinical relevance of additional beneficial effects, i.e., on blood pressure and microalbuminuria, needs to be determined further. Rosiglitazone does not cause hypoglycaemia or gastrointestinal side effects. There is however some concern related to fluid retention, which seems to be an effect of all PPARγ agonists. In patients treated with rosiglitazone, no severe hepatotoxic side effects have been noticed until now. In the treatment of our patients with Type 2 diabetes, drugs like rosiglitazone which directly reduce insulin resistance are very welcome but more data on its combined use with insulin are needed. Additional studies will also explore its long-term effects in sparing β-cell function and reducing diabetes-related complications and atherosclerosis.

Miglitol (Bay m 1099, Bayer) is a second generation α-glucosidase inhibitor. It is a derivative of 1-desoxynojirimycin, and binds reversibly to the brushborder α-glucosidase enzymes. In contrast to its parent drug (acarbose, Bay g 5421, Bayer), miglitol is almost completely absorbed in the small intestine. It has to be taken with each main meal, and through its effect on carbohydrate digestion it blunts the postprandial blood glucose increase. Miglitol has no or a very small effect on fasting blood glucose levels. The blood-glucose lowering effects of miglitol in patients with Type 2 diabetes are lower than those of the frequently-used sulphonylurea compounds. Long-term studies show that a moderate average reduction of HbA1c of 0.3 - 0.7% point from baseline can be achieved. An advantage over sulphonylurea is the effect on serum insulin levels: miglitol therapy leads to slightly lower postprandial levels of serum insulin, whereas chronic sulphonylurea treatment usually increases serum insulin levels. This insulin-sparing effect may, in theory, lead to a lesser weight gain or even no weight gain and reduced risk of hypoglycaemia during chronic treatment. Long-term experience in Type 1 diabetic patients is limited. Similarly, miglitol may lead to reduced postprandial glucose excursions, slightly reduced insulin requirements and perhaps, as a consequence, a lower risk of hypoglycaemia. More long-term data are needed to fully assess to the clinical use of miglitol in these patients.

Objective:To assess which factors influence or predict the efficacy of insulin therapy in subjects with type 2 diabetes, who were poorly controlled despite maximal doses of oral glucose lowering agents.