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Natural GLP-1 Not Impaired in Patients with Type 2 Diabetes

A recent meta-analysis has shown that patients with type 2 diabetes (T2DM) may not have impaired secretion of glucagon-like peptide-1 (GLP-1)….

The study conducted by researchers at Gentofte Hospital at the University of Copenhagen, revealed that T2DM patients had similar levels of GLP-1 secretion as controls after an oral glucose tolerance test (OGTT) or mixed meal.

The study included 275 patients with T2DM and 279 controls, from 22 trials published between 1996 and 2012. Exclusion criteria for trials included studies which used non-specific assays that cross-react with major proglucagon fragment, those which did not provide enough data, and those which dealt with intact GLP-1 only.

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Results from this random effects meta-analysis showed similar GLP levels between T2DM patients and controls when evaluated from peak plasma concentrations, total AUC, time corrected AUC, incremental AUC, and time-corrected incremental AUC. Regression analysis did not show any clear evidence of bias or small study effects (Egger’s test, p>0.1)

Following a repeat of the initial meta-analyses with fixed effects models, primary analysis was confirmed with the exception being that peak plasma total GLP-1 responses were higher in patients with type 2 diabetes compared with controls.

Subgroup analysis revealed that patients with type 2 diabetes had increased GLP-1 response after a liquid mixed meal test and after a 50-g OGTT. However, T2DM patients did have reduced GLP-1 response compared with controls following a solid mixed meal test. Researchers hypothesize this may be due to variations in absorption of nutrients among T2DM patients.

The authors urge that the ‘common knowledge’ of GLP-1 secretion being reduced in T2DM pathophysiology, is a fallacy. Rather, they believe that their findings support the idea that deterioration in GLP-1 effects contribute to the deficiency.

Practice Pearls:

  • Authors of this study believe treatment of T2DM with GLP-1 agonists should be looked upon as a supplementation to normal GLP-1 levels rather than as a substitution to patients with low GLP-1 levels.