e102 Diabetes Care Volume 39, July 2016

COMMENT ON MITA ET AL. Sitagliptin Attenuates the Progression Maria Ida Maiorino,1 Giuseppe Bellastella,1 of Carotid Intima-Media Thickening Dario Giugliano,1 and in Insulin-Treated Patients With Type 2 Katherine Esposito2 Diabetes: The Sitagliptin Preventive Study of Intima-Media Thickness Evaluation (SPIKE): A Randomized Controlled Trial. Diabetes Care 2016;39:455–464 Diabetes Care 2016;39:e102–e103 | DOI: 10.2337/dc16-0475

We read with interest the article by Mita capacity of these drugs from their bene- over a period of 12 months at the same level et al. (1) in Diabetes Care reporting a ficial effect on carotid atherosclerosis. of glycemic control as evidenced by the beneficial effect of sitagliptin on the Throughout the articles, the authors quite identical reduction in post-treatment progression of carotid intima-media state that sitagliptin “attenuated the HbA1c. Although Mita et al. (1,2) adjusted for thickening in Japanese patients with progression of carotid IMT” or alogliptin the differences in HbA1c between interven- type 2 diabetes. This article parallels an- caused “substantial regression of IMT.” tion and control groups, a beneficial effect other article highlighting the prevention The terms progression and regression of improved glycemic control on IMT cannot of the progression of carotid atheroscle- are used without a clear definition of be totally excluded. rosis by alogliptin in patients with type 2 their meaning. Intuitively, progression As large randomized trials did not diabetes (2). The two articles appeared may indicate increased IMT versus base- demonstrate beneficial effects of either in the same journal (Diabetes Care)in line and regression decreased IMT ver- sitagliptin or alogliptin on cardiovascular 2016, were conducted by the same susbaseline.Ifso,aswebelieve,the events among patients with type 2 diabe- group, had the same first author, and authors would have conducted an anal- tes at high cardiovascular risk, Mita et al. had the same (almost identical) baseline ysis based on the categorization of the (1,2) suggest an earlier treatment with values of carotid intima-media thickness changes in IMT into two outcomes: dipeptidyl peptidase 4 inhibitors for pri- (IMT) among the patients with diabetes. decreased/no change of IMT versus mary prevention of cardiovascular disease The two studies also had important dif- baseline (regression) and increased in type 2 diabetes without apparent car- ferences concerning duration of diabetes IMT values versus baseline (progres- diovascular disease. This hope, however, is (17.2 years sitagliptin vs. 9 years aloglip- sion). Next, they would have calculated, already a reality in people with type 2 di- tin), baseline HbA1c (8.1% vs. 7.3%), and in percentage terms, how many patients abetes, as demonstrated by the results insulin use (all sitagliptin patients vs. no progressed or regressed in the interven- of dietary interventional trials with a Med- alogliptin patients). So, at least in Japanese tion groups as compared with the con- iterranean diet (4,5). people, three of the main clinical aspects trol groups. More specifically, they that characterize type 2 diabetesdduration would also have defined regression Duality of Interest. fl of disease, baseline HbA1c, and insulin as a decrease of $0.020 mm in mean No potential con icts of

COMMENTS AND RESPONSES usedare not associated with baseline IMT at the end of follow-up. With this def- interest relevant to this article were reported. – IMT. Moreover, the amelioration of HbA inition, for example, a regression of IMT 1c References after treatment with either sitagliptin or was observed by Esposito et al. (3) in 52% 1. Mita T, Katakami N, Shiraiwa T, et al.; Collab- alogliptin was not associated with of 88 patients with diabetes randomly as-

e-LETTERS orators on the Sitagliptin Preventive Study of changes in IMT, suggesting a largely inde- signed to repaglinide and in 18% of 87 pa- Intima-Media Thickness Evaluation (SPIKE) Trial. pendent effect of the glucose-lowering tients with diabetes assigned to glyburide Sitagliptin attenuates the progression of carotid

1Division of Endocrinology and Metabolic Diseases, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, Second Universityof Naples, Naples, Italy 2Diabetes Unit, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Corresponding author: Maria Ida Maiorino, [email protected]. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. care.diabetesjournals.org Maiorino and Associates e103

intima-media thickening in insulin-treated pa- inhibitor, prevents the progression of carotid type 2 diabetes mellitus. Circulation 2004;110: tients with type 2 diabetes: the Sitagliptin Pre- atherosclerosis in patients with type 2 diabetes: 214–219 ventive Study of Intima-Media Thickness the Study of Preventive Effects of Alogliptin on 4. Estruch R, Ros E, Salas-SalvadoJ,etal.;´ Evaluation (SPIKE): a randomized controlled tri- Diabetic Atherosclerosis (SPEAD-A). Diabetes PREDIMED Study Investigators. Primary preven- al. Diabetes Care 2016;39:455–464 Care 2016;39:139–148 tion of cardiovascular disease with a Mediterra- 2. Mita T, Katakami N, Yoshii H, et al.; Collabo- 3. Esposito K, Giugliano D, Nappo F, Marfella R; nean diet. N Engl J Med 2013;368:1279–1290 rators on the Study of Preventive Effects of Campanian Postprandial Hyperglycemia Study 5. Esposito K, Giugliano D. Mediterranean diet Alogliptin on Diabetic Atherosclerosis (SPEAD-A) Group. Regression of carotid atherosclerosis for primary prevention of cardiovascular dis- Trial. Alogliptin, a dipeptidyl peptidase 4 by control of postprandial hyperglycemia in ease. N Engl J Med 2013;369:674–675