Sulfonylurea insulinotropic agents

Insulinotropic agents directly stimulate the release of insulin from pancreatic j3-cells, and are thus useful only in the treatment of NIDDM. The drugs in this class are often divided into the subclasses of sulfonylureas and glinides. These compounds are structurally related and share a common mechanism of action, and are described together. 

Table 1.3 Structures and Properties of Insulinotropic Agents Sulfonylureas... 

Although the marketed sulfonylureas are all well absorbed, they differ in the time required to reach maximum blood levels (Table 1.3) and in metabolic fate and in rate and mode of elimination. These differences can have important implications for safe use of the various drugs. Accumulation of these agents in vivo can lead to extended episodes of serious or fatal hypoglycemia through overstimulation of insulin release. Insulinotropic drugs, for instance, which are metabolized to active compounds that are eliminated solely by renal excretion, pose a serious risk of hypoglycemia in renally compromised individuals. 

Fig. 6. (continued). In other cases, especially if a more potent drug is to be added, which relies on a similar mechanism (e.g., incretin-mediated insulinotropic activity), one of the previously used antidiabetic agents may need to be discontinued (e.g., when adding a sulfonylurea or an incretin mimetic to a patient previously treated with a DPP-4 inhibitor). Note that sufficient study results (see Fig. 5) are not available for all mentioned combinations to provide a sound scientific basis for their use outside clinical studies. 

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