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Reduced GLP-1 Precedes Type 2 Diabetes

This might be a reason not to use a DPP-4 for those with long standing diabetes…

Reduction in the glucose-regulating hormone glucagon-like peptide-1 (GLP-1) appears to occur before the development of type 2 diabetes and obesity, according to new published research.

Investigator Kristine Færch, PhD, senior research fellow at the Steno Diabetes Center in Gentofte, Denmark, said in a press release that, “We found that GLP-1 is reduced by up to 25% among people with prediabetes and up to 20% among obese people compared to normal-weight people.” “This indicates that the reduction in GLP-1 is not a consequence of type 2 diabetes, but appears much earlier in the disease development and may predispose people to type 2 diabetes.”

See more GLP-1 Agonist Resources

Dr. Færch and colleagues evaluated GLP-1 response to oral glucose in a large study population of lean and obese men and women with normal and impaired glucose regulation. Using an oral glucose tolerance test (OGTT), circulating concentrations of glucose, insulin and GLP-1 were assessed in participants with normal glucose tolerance (n=774), prediabetes (n=523) or screen-detected type 2 diabetes (n=163) from the Danish ADDITION-PRO study (n=1,462).

Results showed that GLP-1 response to an OGTT was 25% lower in women with prediabetes or type 2 diabetes vs. those with normal glucose tolerance. Similarly, 120-minute GLP-1 concentrations were 16% to 21% lower for both men and women with prediabetes or type 2 diabetes, regardless of age or obesity.

In obese and overweight participants, GLP-1 response to an OGTT was 20% lower, as compared with normal-weight participants.

Data also linked higher GLP-1 responses to better insulin sensitivity and beta cell function, older age and lower degree of obesity.

And what is surprising is that they have also found pronounced differences in GLP-1 secretion between men and women. They observed a higher GLP-1 response among women than men, but when glucose tolerance worsens, the decline in GLP-1 secretion is more pronounced in women than in men.

These results could have potential clinical implications as well, the researchers said, noting that GLP-1 analogs may help delay onset of type 2 diabetes.

Plus it may be that for those with long standing diabetes and the reduction of GLP-1, that a DPP-4 compound which helps to prevent the destruction of GLP-1 may not be as effective and for those patients we should most likely start with a GLP-1 compound.

“We should use the findings in prevention strategies for type 2 diabetes, and I hope to see results from longitudinal studies in the future, where we can follow the development in GLP-1 secretion over time in people who develop diabetes,” Dr. Jørgensen said in a press release.

Practice Pearls:

  • Reduction in the glucose-regulating hormone glucagon-like peptide-1 (GLP-1) appears to occur before the development of type 2 diabetes and obesity.
  • A good reason to start with a GLP-1 for those with long standing diabetes, rather than a DPP-4 compound.
  • Possibly using a GLP-1 to prevent diabetes for those with prediabetes.

Færch K et al. Diabetes. 2015;doi:10.2337/db14-1751