Physicians' Academy for Cardiovascular Education

DPP-4 inhibitor attenuates progression and predicts regression of carotid IMT in T2DM

Mita T, Katakami N, Shiraiwa T, et al. - SPIKE trial

In two separate publications, Mita and colleagues report on analyses of data from the SPIKE trial on the effect of the DPP-4 inhibitor sitagliptin on cIMT in T2DM patients receiving insulin therapy.

The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation

Int J Endocrinol. 2017;2017:1925305. doi: 10.1155/2017/1925305

A drawback of strict glycaemic control in CVD patients with advanced atherosclerosis or longstanding T2DM is that the higher risk of hypoglycaemia and weight gain might diminish its benefit [1,2]. Use of oral hypoglycaemic agents (OHA) may reduce these adverse effects of insulin therapy, due to stimulation of endogenous glucose responsive insulin secretion and increased insulin sensitivity.

Add-on therapy of metformin [3] or pioglitazone [4] to insulin therapy was shown not to slow down progression of carotid IMT in patients with T2DM compared with controls. However, it was reported that sitagliptin, a DPP-4 inhibitor, attenuated progression of carotid IMT in insulin-treated patients with T2DM as compared with conventional treatment without increasing risk of hypoglycaemia, in the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation (SPIKE). [5]. The effect of DPP-4 inhibition on regression of carotid IMT is largely unknow.

This study therefore examined whether sitagliptin has a beneficial effect on regressing carotid IMT in a post hoc analysis of the SPIKE trial [5], as the original article focussed on IMT progression. 282 Insulin-treated Japanese T2DM patients without a history of apparent CVD were randomised to sitagliptin or conventional treatment, and 137 patients in each group were included in the full analysis set. Ultrasonography of the carotid arteries was performed at the start of the study, and after 52 and 104 weeks.

This analysis suggests that the DPP-4 inhibitor sitagliptin is associated with regression of carotid atherosclerosis in insulin-treated patients with T2DM, but free from apparent CVD. Sitagliptin treatment was an independent predictor of carotid IMT, irrespective of several possible risk factors for atherosclerosis, background therapies that might have antiatherosclerotic effects and/or changes in metabolic parameters.

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Changes in carotid intima-media thickening in patients with type 2 diabetes mellitus: Subanalysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation

J Diabetes Investig. 2017 Mar;8(2):254-255. doi: 10.1111/jdi.12559

In a letter to the editor in the Journal of Diabetes Investigation, the same group reported on a comparison of the efficacy of treatment with sitagliptin with that of other modalities on the progression of carotid IMT in prespecified subgroups of the SPIKE trial, with the aim to identify characteristics of patients who benefited most from sitagliptin treatment in terms of decrease in IMT.

Thus, these data suggest that treatment with DPP-4 inhibitors may prevent progression of carotid atherosclerosis regardless of disease burden. Previously, it had been shown that treatment with statins and ACE-inhibitors reduced the progression of carotid atherosclerosis in patients with T2DM. Sitagliptin was now shown to further attenuate carotid IMT progression in patients already receiving these therapies.

References

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Find the article in Int J Endocrinol online Find the letter to the editor in J Diabetes Investig. online