Non-insulin anti-diabetic drugs: An update on pharmacological interactions

Ruscica, Massimiliano; Baldessin, Ludovico; Boccia, Delia; Racagni, G.; Mitro, Nico

doi:10.1016/j.phrs.2016.11.005

Cited by 21 publications

(14 citation statements)

References 97 publications

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“…Agonists of PPAR-γ belong to the thiazolidinedione (TZDs) drug class and are currently in use for T2D [ 114 ]. Pioglitazone and rosiglitazone are the only two drugs available.…”

Section: Ppar-γ Agonistsmentioning

confidence: 99%

PPAR Agonists and Metabolic Syndrome: An Established Role?

Botta

Audano

Sahebkar

et al. 2018

IJMS

199

129

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Therapeutic approaches to metabolic syndrome (MetS) are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs) are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs), blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate) and omega-3 fatty acids, are powerful TG-lowering agents. They mainly affect TG catabolism and, particularly with fibrates, raise the levels of high-density lipoprotein cholesterol (HDL-C). PPAR-γ agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-α/δ agonists, e.g., elafibranor, have been designed to achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to the insulin-sensitizing and antihyperglycemic effects of glitazones. They also hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD) which is closely associated with the MetS. The PPAR system thus offers an important hope in the management of atherogenic dyslipidemias, although concerns regarding potential adverse events such as the rise of plasma creatinine, gallstone formation, drug–drug interactions (i.e., gemfibrozil) and myopathy should also be acknowledged.

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“…Agonists of PPAR-γ belong to the thiazolidinedione (TZDs) drug class and are currently in use for T2D [ 114 ]. Pioglitazone and rosiglitazone are the only two drugs available.…”

Section: Ppar-γ Agonistsmentioning

confidence: 99%

PPAR Agonists and Metabolic Syndrome: An Established Role?

Botta

Audano

Sahebkar

et al. 2018

IJMS

199

129

View full text Add to dashboard Cite

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“…Thus, PPARγ represents an interesting pharmacological target which is able to simultaneously modulate several of the underlying pathologies of diabetes and metabolic syndromes 11 . Pioglitazone (PIO) is a thiazolidinedione drug and a PPAR γ agonist that acts as an insulin sensitizer, which has been used to treat T2DM for over a decade 7 and has been shown to reduce cardiovascular events 12 . PIO has pleiotropic effects on insulin secretion, lipid and adipose tissue metabolism, body fat distribution and vascular endothelial function 6 , 7 , 12 .…”

Section: Introductionmentioning

confidence: 99%

“…Pioglitazone (PIO) is a thiazolidinedione drug and a PPAR γ agonist that acts as an insulin sensitizer, which has been used to treat T2DM for over a decade 7 and has been shown to reduce cardiovascular events 12 . PIO has pleiotropic effects on insulin secretion, lipid and adipose tissue metabolism, body fat distribution and vascular endothelial function 6 , 7 , 12 . It was shown to effectively attenuate oxidative stress, inflammation and apoptosis 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats

Hamza

Fikry

Abdallah

et al. 2018

Sci Rep

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This study was designed to assess whether the protective effects of bone marrow-derived mesenchymal stem cells (MSCs) against diabetes could be enhanced by pioglitazone (PIO), a PPARγ agonist. Combined MSCs and PIO treatments markedly improved fasting blood glucose, body weight, lipid profile levels, insulin level, insulin resistance, β cell function. Those protective effects also attenuated both pancreatic lesions and fibrosis in diabetic rats and decreased the depletion of pancreatic mediators of glycemic and lipid metabolism including peroxisome proliferator-activated receptor alpha (PPARα), PGC-1α, GLP-1 and IRS-2. Cardiac biogenesis of diabetic groups was also improved with MSCs and/or PIO treatments as reflected by the enhanced up-regulation of the expressions of cardiac IRS1, Glucose transporter 4, PGC-1, PPARα and CPT-1 genes and the down-regulated expression of lipogenic gene SREBP. The combination of MSCs and PIO also potentiated the decrease of abnormal myocardial pathological lesions in diabetic rats. Similarly, the inhibitory effects of MSCs on diabetic cardiac fibrosis and on the up regulations of TGF-β, collagen I and III gene expressions were partial but additive when combined with PIO. Therefore, combined therapy with PIO and BMCs transplantation could further potentiate the protective benefit of MSCs against diabetes and cardiac damage compared to MSCs monotherapy.

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“…Drug-drug interactions with SGLT2i and GLP-1RA therapies do not appear to be a significant clinical issue for medications that are commonly used in surgical patients. 32,33 However, it is important to note that both classes of medications can lead to hypoglycemia, especially when coadministered with other antihyperglycemia medications. In addition, SGLT2is cause an osmotic diuresis and intravascular volume contraction, so it is important to closely monitor renal function and use caution when treating with SGLT2is in conjunction with other therapies that may lead to acute renal failure, such as diuretics or nonsteroidal antiinflammatory drugs.…”

Section: Specific Implications For Surgeonsmentioning

confidence: 99%

New antihyperglycemic medications with cardiovascular protection for patients with diabetes: What do surgeons need to know?

Pagidipati

Lópes

2019

The Journal of Thoracic and Cardiovascular Surgery

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Although diabetes mellitus has long been known to significantly increase the risk of cardiovascular disease (CVD), 1 traditional anti-hyperglycemic medications have failed to improve cardiovascular (CV) outcomes. 2-4 However, in the past 4 years, major breakthroughs have been made in this field. Two new classes of antihyperglycemia medications, sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), have recently been shown to improve not only glycemic control but also CV outcomes in patients with type 2 diabetes mellitus (T2DM). Because the proportion of patients with T2DM undergoing coronary artery bypass grafting (CABG) and other surgeries is rapidly increasing, 5 surgeons will begin to encounter these medications with greater frequency. Here we review the essential information that surgeons need to be aware of as they participate in the teambased care of patients with T2DM and CVD. EVIDENCE OF CV BENEFITS WITH SGLT2is SGLT2is inhibit glucose reabsorption and increase glucose excretion in the kidney, thus leading to so-called sweet pee and improved glycemic control. 6 Three CV outcomes trials with SGLT2is have been published to date (Table 1), 7-13 and all have shown CV benefits. In the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients trial, 7020 patients with T2DM and known CVD were randomized to empagliflozin or placebo. 7 After a median of 3.1 years, the primary end point of 3-point major adverse cardiovascular events (MACE) (ie, CV death, myocardial infarction [MI], or stroke) was significantly reduced with empagliflozin treatment (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.74-0.99; P<.04). This was largely driven by a reduction in CV death (HR, 0.62; 95% CI, 0.49-0.77; P <.001). Of note, significant reductions in all-cause mortality (32%) and heart failure (HF) (35%) were also observed. Canagliflozin was evaluated in the Canagliflozin Cardiovascular Assessment Study (CANVAS) program, which consisted of 2 sister trials (CANVAS and CANVAS-Renal) in primary and secondary prevention patients with T2DM. 8 Over a median follow-up of 3.6 years, 3-point MACE was significantly reduced with canagliflozin (HR, 0.86; 95% CI, 0.75-0.97; P ¼ .02). Other exploratory outcomes indicated a potential benefit for death from HF (HR, 0.78; 95% CI, 0.67-0.91) and for a composite outcome of progression of renal disease (HR, 0.60; 95% CI, 0.47-0.77). An approximately 2-fold increase in the risk for lower-leg amputations was observed with canagliflozin (HR, 1.97; 95% CI, 1.41-2.75). The final SGLT2i with published CV outcomes data is dapagliflozin, which was evaluated in the Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 trial. 9 This trial differed from the others in that it enrolled a ''healthier'' population (approximately 60% were primary prevention patients, and all had an estimated creatinine clearance 60 mL/ min), and it evaluated coprimary end points of 3-point MACE and a composit...

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Non-insulin anti-diabetic drugs: An update on pharmacological interactions

Cited by 21 publications

References 97 publications

PPAR Agonists and Metabolic Syndrome: An Established Role?

PPAR Agonists and Metabolic Syndrome: An Established Role?

Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats

New antihyperglycemic medications with cardiovascular protection for patients with diabetes: What do surgeons need to know?

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