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DPP-4 Inhibitors Protect against Hypoglycemia

Mice treated with DPP-4 inhibitors also showed an increase in production of their own glucagon…

Siri Malmgren, a researcher at Lund University, stated that, “If these inhibitors also prove effective in humans against low blood sugar, then this supports the idea that the area of application of these drugs could be broadened to include persons with diabetes that is difficult to control and suffer from frequent hypoglycemias.”

Malmgren, added that, “In order to be able to offer people with diabetes more reliable treatment, it is important that their medication supports the body’s own defenses against hypoglycemia.”

“One of the advantages of DPP-4 inhibition as a treatment for diabetes is the very low risk of hypoglycemia. Through Dr. Malmgren’s important work, a fundamental new principle for this has been identified. We are now beginning to understand why DPP-4 inhibitors reduce the risk of this serious side effect,” said Professor Bo Ahrén, the principal investigator for the study.

Mice treated with DPP-4 inhibitors were seen to have much better protection against hypoglycemia than mice that were not given DPP-4 inhibitors. Their own production of glucagon also increased.

DPP-4 inhibitors stimulate the body’s own insulin production and work by raising the levels of another hormone – GIP – that is secreted in the intestines when food is ingested. Giving mice high doses of this hormone also protected them against hypoglycemia and increased their glucagon levels.

“We believe that DPP-4 inhibitors not only lower blood sugar but also provide direct protection against hypoglycemia, at least in mice, and that they do this by increasing levels of the hormones GIP and glucagon”, said Malmgren.

The researchers also reached the conclusion that GIP, which has previously been considered to lower blood sugar, in fact normalizes blood sugar levels.

“Our findings could lead to new areas of application for existing drugs. We don’t know all there is to know about the medicines we have, and once we have full insight into their mechanisms of action we can use them more effectively.”

Practice Pearls:

  • One of the advantages of DPP-4 inhibition as a treatment for diabetes is the very low risk of hypoglycemia.
  • DPP-4 inhibitors not only lower blood sugar but also provide direct protection against hypoglycemia.
  • GIP, which has previously been considered to lower blood sugar, in fact normalizes blood sugar levels.

Diabetologia. Feb 26, 2015