DPP4-inhibitor decelerates the progression of atherosclerosis in type 2 diabetes patientsLiterature - Mita et al., Diabetes Care 2016
Sitagliptin Attenuates the Progression of Carotid Intima-Media Thickening in Insulin-Treated Patients With Type 2 Diabetes: The Sitagliptin Preventive Study of Intima-Media Thickness Evaluation (SPIKE)
A Randomized Controlled Trial
Mita T, Katakami N, Shiraiwa T, et al.
Diabetes Care 2016; published online ahead of print
BackgroundIn patients with type 2 diabetes mellitus and established atherosclerosis, intensive glucose control was shown to have no significant effect on the rates of major cardiovascular events, and according to some data, it even increased mortality [1,2]. These results have been partially explained by frequent hypoglycaemic episodes and weight gain, caused by the intensive insulin treatment . It is postulated that the combination therapy of reduced insulin doses and oral hypoglycaemic agents may be of benefit for these patients [4,5].
Sitagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor that increases insulin secretion and suppresses glucagon release [6,7]. The addition of DPP-4 inhibitors to insulin therapy has been reported to have specific advantages, like reducing the frequency of hypoglycemia and weight gain . Preclinical data suggest that DPP-4 inhibitors could have beneficial effects on atherosclerosis .
In this multicenter, randomised study, the effects of sitagliptin compared with conventional treatment on carotid intima-media thickness (IMT) was investigated, in insulin-treated type 2 diabetes mellitus patients.
Main results• Sitagliptin significantly reduced the mean IMT and the left maximum IMT of common carotid arteries, compared with conventional treatment:
- Mean IMT change: -0.029 (SE: 0.013) vs. 0.024 (SE: 0.013) mm, P = 0.005
- Left maximum IMT change: -0.065 SE: 0.027) vs. 0.022 (SE: 0.026) mm, P = 0.021
- Right maximum IMT change: -0.007 (SE: 0.031) vs. 0.027 (SE: 0.031) mm, P = 0.45
The findings were similar after adjustment for several confounders (grouped in models).
• Sitagliptin, compared to conventional treatment was associated with significant improvements of
- HbA1C %: -0.5 ± 1.0% vs. -0.2 ± 0.9%; P = 0.004
- C-peptide (ng/mL): 0.3 ± 0.8 vs. 0.0 ± 0.6; P = 0.02
• There were no significant differences between treatment groups in regard to
- fasting blood glucose concentrations,
- other risk factors for atherosclerosis, such as BMI, blood pressure, and lipid parameters
- the use of antihypertensive drugs and lipid-lowering agents
- the levels of various markers of inflammation and endothelial damage
ConclusionIn insulin-treated type 2 diabetes mellitus patients without cardiovascular disease, sitagliptin decelerated the progression of carotid IMT compared with conventional treatment. The results of this study support the hypothesis according to which early and effective intervention with DPP-4 inhibitors before the development of advanced atherosclerosis may be beneficial for the prevention of carotid IMT progression in these patients.
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1. Gerstein HC, Miller ME, Byington RP, et al. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545–2559
2. Duckworth W, Abraira C, Moritz T, et al. VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129–139
3. Frier BM, Schernthaner G, Heller SR. Hypoglycemia and cardiovascular risks. Diabetes Care 2011;34(Suppl. 2):S132–S137
4. Strowig SM, Avil ´ es-Santa ML, Raskin P. Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and troglitazone in type 2 diabetes. Diabetes Care 2002;25:1691–1698
5. Nemoto M, Tajima N, Kawamori R. Efficacy of combined use of miglitol in type 2 diabetes patients receiving insulin therapy-placebo controlled double-blind comparative study. Acta Diabetol 2011;48:15–20
6. Katsuno T, Ikeda H, Ida K, et al. Add-on therapy with the DPP-4 inhibitor sitagliptin improves glycemic control in insulin-treated Japanese patients with type 2 diabetes mellitus. Endocr J 2013;60:733–742
7. Shimoda S, Iwashita S, Ichimori S, et al. Efficacy and safety of sitagliptin as add-on therapy on glycemic control and blood glucose fluctuation in Japanese type 2 diabetes subjects ongoing with multiple daily insulin injections therapy. Endocr J 2013;60:1207–1214
8. Rosenstock J, Rendell MS, Gross JL, et al. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab 2009;11:1145–1152
9. Shah Z, Kampfrath T, Deiuliis JA, et al. Longterm dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation 2011;124:2338–2349