Comparison of Antidiabetic Medications during the Treatment of Atherosclerosis in T2DM Patients

Abstract

Type 2 diabetes is often associated with arterial atherosclerosis in large blood vessels. We set out to elucidate whether commonly used antidiabetic drugs metformin, sitagliptin, and pioglitazone will reduce atherosclerosis in T2DM patients. We enrolled 176 individuals with type 2 diabetes, which were divided into four treatment groups according to different oral drugs: metformin alone, sitagliptin alone, pioglitazone alone, or combination of metformin and sitagliptin. We assessed changes in glycometabolism, lipid metabolism, cytokine released, and carotid artery intima-media thickness as the readout for improvement in atherosclerosis. HbA1c levels were significantly decreased in all treatment groups (p < 0.05), and FBG levels were also decreased in metformin and combined groups (p < 0.05). In addition, we found IL-6 levels significantly decreased in all treatment groups (p < 0.05). Treatment with pioglitazone showed a significant increase in BMI, HDL, and ADPN levels (p < 0.05). We also observed a significant decrease in NHDL levels in the combined treatment group (p < 0.05). Our data revealed that in addition to hypoglycemic properties of metformin, sitagliptin, and pioglitazone, these drugs also have the potential to promote an anti-inflammatory response. Therefore, combination therapy may be more beneficial for reducing atherosclerosis in patients with type 2 diabetes. The clinical trial is registered with ChiCTR-ORC-17010835.

Effect of pioglitazone, as antidiabetic agent, on atheroma regression in type 2 diabetic patients: a systematic review and meta-analysis

“…Through its antiatherogenic effects, by means of a reverse cholesterol transport pathway, elevated levels of HDL are an established method to decrease the risk of cardiovascular injury. The search for new and effective drugs for this purpose continues, and of particular interest are drugs that can increase endogenous levels of HDL, such as pioglitazone, rather than the use of exogenous substances that only mimic the effect of HDL [19]. Kardassis and colleagues showed that glitazones can improve the expression of HDL genes which go in agreement with our findings [28].…”

“…Decreased HDL levels are an established part of every level of atheroma pathophysiology whereby the mechanisms of (1) inhibiting monocyte adhesion to endothelial cells at sites of plaque formation, (2) promoting NO production which suppresses proliferation of the plaque, (3) promoting fibrinolysis, and (4) preventing intra-plaque hemorrhage and many other pleiotropic effects are lost in the setting of decreased HDL levels [19].…”

Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: narrative review and meta-analysis

“…DPP4i has been proposed to reduce the overproduction of proinflammatory cytokines and mediators, such as IL-1, IL-6 and tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), possibly mitigating the clinical course of COVID-19. In several human studies, a treatment with sitagliptin significantly decreased plasma concentrations of IL‐6 [ 36 ] and CRP [ 37 ]. In another study, a treatment with vildagliptin was associated with a significant reduction in IL-6 levels [ 38 ].…”

Anti-inflammatory properties of antidiabetic drugs: A “promised land” in the COVID-19 era?

“…IL-6 levels were non-significantly decreased at 3 months among 24 sitagliptin-treated T2DM patients (from 3.5 ± 0.6 to 2.7 ± 0.3 pg/mL, p = ns), 41 whereas they were significantly lowered by sitagliptin in 22 T2DM patients at 12 weeks (by 24%, p < 0.05), 42 as well as at 12 months (from 15.8 ± 6.2 to 12.8 ± 4.3 pg/mL, p = 0.03) in 31 T2DM patients. 53 …”