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Translation of a-t 2020; 51: 7
 

SIDE EFFECTS

INTESTINAL OBSTRUCTION WITH INCRETIN MIMETICS

The incretin mimetics approved to treat type 2 diabetes include GLP-1 analogues such as dulaglutide (TRULICITY; a-t 2015; 46: 27-8) and DPP-4 inhibitors such as sitagliptin (JANUVIA, XELEVIA; a-t 2007; 38: 56-7). While the summary of product characteristics (SPCs) for all GLP-1 agonists lists intestinal obstruction as a side effect that occurs very rarely to uncommonly (1,2), there is as yet no such reference for the DPP-4 inhibitors known as gliptins (3). In late 2019, our French sister journal La Revue Prescrire reported on a risk signal for intestinal obstruction in connection with both incretin mimetic groups (4). By assessing the spontaneous reports of intestinal obstruction documented in the WHO adverse events database between 2007 and 2017, a French pharmacovigilance centre identified 452 reports in patients taking these substances. A total of 420 events were graded as serious, and 11 patients died. The harmful effect was observed significantly more frequently in patients taking incretin mimetics compared to other anti-diabetic drugs, with the risk signal for DPP-4 inhibitors (reporting odds ratio [ROR] 8.7; 95% confidence interval [CI] 7.3-10.3) greater than for GLP-1 agonists (ROR 3.1; 95% CI 2.5-3.7) (4,5).

While positive effects on cardiovascular endpoints have been demonstrated for the GLP-1 agonists, at least for some derivatives such as liraglutide (VICTOZA, a-t 2016; 47: 67 and e a-t 7/2016), no long-term benefit has yet been identified for DPP-4 inhibitors (a-t 2019; 50: 119-20). Disorders of intestinal passage including intestinal obstruction should be taken into account when using incretin mimetics and patients should have the corresponding symptoms explained to them, -Ed.

1Lilly: SPC TRULICITY, version of October 2019
2AstraZeneca: SPC BYDUREON, version of February 2019
3e.g. MSD: SPC JANUVIA, version of August 2018
4La Revue Prescrire 2019; 39: 908
5GUDIN, B. et al.: Fundam. Clin. Pharmacol. 2019; 33 (Suppl. 1): 53 (abstract PS1-025)

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