Oral Combination Therapy

The combination of sulfonylureas with other noninsulinotropic agents results in additive effects and potently lowers blood glucose. The combination of metformin with sulfonylureas or meglitinides is frequently used, and additionally lowers HbA1c by 1% to 2%, depending on the dose of metformin added. A dose-related increase has been shown to occur to a ceiling of 2g metformin added to the insulin releaser per day in two doses (31). However, the mortality in the combination therapy group was increased compared with sulfonylurea monotherapy in the UKPDS (32). This has been attributed to an exceptionally low mortality in the sulfonylurea monotherapy group. However, similar trends were observed in a population-based observational study, indicating an urgent need for further studies of this combination (33). Similar improvements of blood glucose were reported for the combination of meglitinides with metformin (18) and for combinations of thiazolidinediones or a-glucosidase inhibitors and sulfonylureas. In all combinations, HbA1c was lowered by 1% to 2%, in addition to the effect of the insulinotropic agent.

Most patients will, in fact, require more than one agent to achieve treatment goals of HbA1c < 7%. The choice may be individualized, depending on body weight, compliance, kidney function, and individual response to the treatment. The combination of insulinotropic agents with thiazolidinediones is highly effective in lowering blood glucose, but also additively increases body weight by 2 to 6 kg. The combination with a-glucosidase inhibitors was also shown to lower HbAlc by about 1%, but the lowering of fasting plasma glucose takes several weeks—for unknown reasons. This combination causes no additive weight gain. A combination with rimonabant, an inverse agonist of the cannabinoid receptor type 1 (CB1), was shown to lower HbA1c and body weight by about 5 kg.

Since all diabetes trials observed a positive relation between blood glucose and the occurrence of late complications, this approach is rational and well-justified, based on current evidence.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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