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PubMed1962

[Antidiabetics].

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Hypoglycemic Agents↗
PubMed1998

Repaglinide--prandial glucose regulator: a new class of oral antidiabetic drugs.

The highest demand on insulin secretion occurs in connection with meals. In normal people, following a meal, the insulin secretion increases rapidly, reaching peak concentration in the blood within an hour. The mealtime insulin response in patients with Type 2 diabetes is blunted and delayed, whereas basal levels often remain within the normal range (albeit at elevated fasting glucose levels). Restoration of the insulin secretion pattern at mealtimes (prandial phase)--without stimulating insulin secretion in the 'postabsorptive' phase--is the rationale for the development of 'prandial glucose regulators', drugs that are characterized by a very rapid onset and short duration of action in stimulating insulin secretion. Repaglinide, a carbamoylmethyl benzoic acid (CMBA) derivative is the first such compound, which recently has become available for clinical use. Repaglinide is very rapidly absorbed (t(max) less than 1 hour) with a t1/2 of less than one hour. Furthermore, repaglinide is inactivated in the liver and more than 90% excreted via the bile. The implications of tailoring repaglinide treatment to meals were examined in a study where repaglinide was dosed either morning and evening, or with each main meal (i.e. breakfast, lunch, dinner), with the total daily dose of repaglinide being identical. The mealtime dosing caused a significant improvement in both fasting and 24-hour glucose profiles, as well as a significant decrease in HbA1c. In other studies, repaglinide caused a decrease of 5.8 mmol x l(-1) in peak postprandial glucose levels, and a decrease of 3.1 mmol x l(-1) in fasting levels with a reduction in HbA1c of 1.8% compared with placebo. In comparative studies with either sulphonylurea or metformin, repaglinide caused similar or improved control (i.e. HbA1c, mean glucose levels) and the drug was well tolerated (e.g. reported gastrointestinal side-effects were more than halved when patients were switched from metformin to repaglinide). A hallmark of repaglinide treatment is that this medication follows the eating pattern, and not vice versa. Hence the risk of developing severe hypoglycaemia (BG < or = 2.5 mmol x l(-1)) in connection with flexible lifestyles should be reduced. This concept was examined in a study in which patients well controlled on repaglinide skipped their lunch on one occasion. When a meal (i.e. lunch) was skipped--so was the repaglinide dose, whereas in the comparative group on glibenclamide the recommended morning and evening doses were taken. Twenty-four per cent of the patients in the glibenclamide group developed severe hypoglycaemia, whereas no hypoglycaemic events occurred in the group receiving repaglinide. However, in long-term studies the overall prevalence of hypoglycaemia was similar to that found with other insulin secretagogues. In summary, current evidence shows that the concept of prandial glucose regulation offers good long-term glycaemic control combined with a low risk of severe hypoglycaemia with missed meals. The concept should meet the needs of Type 2 diabetic patients, allowing flexibility in their lifestyle.

Administration, Oral↗
PubMed1998

Estimates on the incidence of antidiabetic drug-induced severe hypoglycaemia in Hong Kong.

In order to estimate the incidence of severe hypoglycaemia (defined as episodes severe enough to require hospitalization in general medical wards) among known diabetics in Hong Kong in 1990, both the total number of such admissions to the Prince of Wales Hospital and the age and sex distribution and number of known diabetics among its catchment population were defined. The latter was derived from the 1991 census and two studies or the prevalence of diabetes mellitus in Chinese subjects in the New Territories East region in 1987 and 1990. The incidence of severe hypoglycaemia was generally higher in women than in men and in older than in younger subjects. The incidence was 15-19 times higher in subjects aged >or=60 years than in those aged <or=59 years (men 3.51 versus 0.17%, women 6.86 versus 0.43%, overall 5.16 versus 0.29%). As many as 24.16% of the subjects aged 70-74 years had severe hypoglycaemia in 1990. The overall incidence of severe hypoglycaemia in all known diabetics was 1.40%. Based on the data from a drug utilization study (70.24% and 5.93% of diabetics receiving sulphonylureas and insulins, respectively), it could be estimated that in 1990, the incidence of hypoglycaemia requiring hospitalization in general medical wards was 1.42% for sulphonylureas and 6.84% for insulins.

Journal Article↗
PubMed1999

Antioxidant action and potential antidiabetic properties of an isoflavonoid-containing soyabean phytochemical extract (SPE).

The potential role of oestrogenic agents, antioxidants and intestinal glucose-uptake inhibitors in the treatment of diabetes is briefly reviewed. Reports in the literature suggest that oestrogen replacement therapy may favourably modulate glucose homeostasis. A soya phytochemical extract (SPE) containing the isoflavone phytoestrogens genistein and daidzein (mostly in their glycone forms as genistin and daidzin) was investigated as an antioxidant and modulator of intestinal glucose-transport. In the present study, SPE was found to protect against glucose-induced oxidation of human low density lipoproteins (LDL) in vitro. Equol (a gut bacterial metabolite of daidzein) was a more effective antioxidant than daidzein or genistein in this system and was of similar antioxidant potency to the dietary flavonols quercetin and kaempferol and to the endogenous antioxidant 17beta-oestradiol. SPE was found to be an inhibitor of glucose uptake into rabbit intestinal brush border membrane vesicles in vitro, though of weaker potency than the classical sodium dependent glucose transporter (SGLT) inhibitor, phlorizin. Thus SPE displays a range of properties which may be of benefit in diabetes, namely as an oestrogenic agent, an inhibitor of intestinal glucose-uptake and a preventive agent for glucose-induced lipid peroxidation.

Animals↗