Within the next year, all of us will be looking at insulin resistance and diabetes in different ways than we have before. Up to now, a primary focus of therapy has been the suppression of hyperglycemia. In the future, the focus may also include increasing tissue sensitivity to insulin. We now understand how important this is to the success of therapy for type II diabtes, and for the first time, we may couple this understanding with pharmacological agents with this effect. We hope that within the next 6 months, we will have three such drugs: metformin (Glucophage)(Bristol-Myers-Squibb), glimepramide (Amaryl)(Hoechst-Marion-Roussel) and acarbose (Precose)(Bayer). Not only may each of these drugs increase tissue responsiveness to insulin, but they may also do it by different mechanisms, which may be additive.
Metformin is the only one that has already been released. This biguanide increases muscle utilization of glucose, and reduces hepatic glucose production. It may also work, by reducing the appetites of people who take it. It improves hyperglycemia, but it does not cause hypoglycemia. It reduces serum triglycerides and improves the HDL/LDL ratio. It has none of the risks of lactic acidoses of the older biguanide (phenformin) so long as it is used in people without significant renal disease or any other condition, such as hypoxia, which may increase the generation of lactate.
Acarbose is a gel-like substance, which is nonabsorbable. It appears to attenuate glucose absortion. As metformin, it probably reduces the appetite in patients via its GI side effects.
Glimepramide will probably come out next. This sulfonylurea has little effect on insulin release. It appears to increase the peripheral action of existing insulin. In vitro, it has less cardiac effect than any other sulfonylurea studied so far.
WARNING:
The unusual double-egg shape, colors, and the size of Amaryl pills are almost identical to the shape, colors, and size of a standard brand of thyroid hormone, Levoxyl (manufactured by Daniels Pharmaceuticals).
If the patient is on both Amaryl and Levoxyl, or if the patient is in a setting such as a hospital or nursing home where both pills are available in containers located nearby to each other, EXTREME CAUTION must be taken that the medications are not mistaken for each other!
Overall, these drugs may achieve a different clinical outcome than exogenous insulin or traditional sulfonylureas. Recent studies have suggested that exogenous insulin or sulfonylureas may increase serum insulin levels and increase body weight. These drugs either cause no change in insulin levels and weight, or their use may be associated with a reduction versus placebo-treated patients. These data also suggest that, in obese patients with type II diabetes, the traditional treatments they were receiving may have been responsible, at least in part, for the weight gain that was seen frequently in these people.
Dr. Hing-Chung Lam