Drugs Suggested for Both Type 1 and 2 Diabetes

Drugs Suggested for Both Type 1 and 2 Diabetes

a -Glucosidase Inhibitors. These include acarbose (an insoluble a-glucosi- dase inhibitor) and miglitol (a soluble short-term a-glucosidase inhibitor). Both are alternative drugs, orally active, that act at the brush border of the

small intestine by inhibiting a-glucosidase, thus interfering with the conversion of disaccharides to monosaccharides. Therefore, they delay the digestion of complex carbohydrates and disaccharides by reducing absorption of glucose and flattening the postprandial glucose level. Acarbose is an antihyperglycemic agent which has been proposed as add-on therapy in type 2 diabetic patients not well controlled with diet alone, sulfonylureas, metformin or insulin, and in type 1 diabetic patients with large meal-related plasma glucose excursions. Treatment with acarbose has several effects (table 4). The efficacy and side

Table 4. Effects of acarbose treatment Delay in digestion of complex carbohydrates Increase in breath hydrogen

Reduction in glucose absorption Decrease in nutrient-stimulated insulin Decrease in postprandial glycemia

secretion

Decrease in postprandial insulinemia Decrease in nutrient-stimulated GIP secretion Decrease in postprandial C-peptide level

Decrease in fasting serum triglycerides Decrease in fasting glycemia

Decrease in fasting serum cholesterol (only in some diabetic patients)

effects of this drug seem to depend on national nutrition habits. Numerous controlled studies in type 2 diabetes have demonstrated the usefulness of

acarbose, at a dose of 150–600 mg/day, in decreasing fasting and postprandial glucose levels as well as HbA 1c concentrations (mean decrease of 0.7%), whether acarbose was given as first-line therapy in diet-treated diabetic patients or in combination in individuals already receiving a sulfonylurea, metformin or insulin. Only a few controlled studies have compared the effects of acarbose with those of either sulfonylurea or metformin, yielding controversial results.

In type 1 diabetic patients, a small reduction of HbA 1c levels was also reported after addition of acarbose to insulin therapy, which in some cases allowed a slight reduction of daily insulin needs. All these favorable biological effects occurred without exposing the patient to hypoglycemia or weight gain. A few studies have also reported favorable effects on postprandial lipid profile and some other vascular risk factors.

In a recent study, acarbose was suggested as a first-line drug in the treat- ment of either type 2 diabetic patients with mild elevation of glycemia, alone or as an adjunct to sulfonylureas, or in type 1 patients associated with insulin

therapy. Acarbose was reported to reduce HbA 1c by 0.4–1.5% with a maximum effect at 3 months, which was further well maintained.

In the UKPDS, glibenclamide as well as insulin therapy induced a weight gain of 4.8 kg, whereas the intake of acarbose (probably through reduction of hyperinsulinemia) was associated with a mild weight loss (0.7 kg after

1 year follow-up). Acarbose also has the advantage that it does not cause hypoglycemia, being an antidiabetic rather than a hypoglycemic agent. It is well tolerated in the dose range of 25–250 mg t.i.d., but small doses (from 25 to 50 mg t.i.d.) can also be effective and cause only fewer gastrointestinal side effects. The latter include meteorism, flatulence, nausea, borborygmus, diarrhea and abdominal cramps or distension. The frequency of gastrointestinal com- plaints is not related to the acarbose dose and decreases over time. Adaptation of intestinal enzyme activity may account for the diminution of intestinal side 1 year follow-up). Acarbose also has the advantage that it does not cause hypoglycemia, being an antidiabetic rather than a hypoglycemic agent. It is well tolerated in the dose range of 25–250 mg t.i.d., but small doses (from 25 to 50 mg t.i.d.) can also be effective and cause only fewer gastrointestinal side effects. The latter include meteorism, flatulence, nausea, borborygmus, diarrhea and abdominal cramps or distension. The frequency of gastrointestinal com- plaints is not related to the acarbose dose and decreases over time. Adaptation of intestinal enzyme activity may account for the diminution of intestinal side

bose, when compared to that of older oral antidiabetic agents, is justified since no study has yet demonstrated its potential benefit on the complications and long-term prognosis of diabetic patients.

Insulin-Like Growth Factor I (IGF-I ). IGF-I (or somatomedin C) is one of the major components of nonsuppressible insulin-like activity. IGF-I and insulin share common steps in signal transduction, and the action of IGF-I on carbohydrate metabolism is preserved in certain insulin-resistant states. GH hypersecretion and reduced circulating IGF-I levels are prevalent in poor- controlled insulin-dependent diabetes. Recently, both bacteria and fungi have been engineered to produce sufficient quantities of recombinant human IGF-I (rhIGF-I), so that rhIGF-I has been proposed as a potential therapeutic agent in the treatment of both type 1 and type 2 diabetic patients. rhIGF-I not only improves glucose tolerance and increases insulin sensitivity, but also improves insulin secretion in response to intravenous glucose. It is uncertain whether this is a direct effect of rhIGF-I on the pancreatic b-cell or an effect secondary to improved glycemic control (reduced glucose toxicity). The most appropriate dose to achieve efficacy and safety remains to be defined.

Nicotinamide. This soluble vitamin of the B group, alone or with sulfonylu- reas, increases serum C-peptide release in type 1 patients as well as in type 2 diabetic patients with sulfonylurea failure, improving glycemic control.