The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes

Kim, Gwang Sil; Park, Joong Hyun; Won, Jong Chul

doi:10.3803/enm.2019.34.2.106

Cited by 15 publications

(18 citation statements)

References 71 publications

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“…In addition, GLP-1 agonists increase natriuresis [17], reduce blood pressure, reduce inflammation, reduce ischemic injury, increase heart rate, increase plaque stabilization and decrease smooth muscle proliferation. It has been suggested that the positive effects of GLP-1 agonists on cardiovascular disease may be the result of a direct action on the arteriosclerotic process [66]. All these processes may leave an imprint on GLP-1 agonists' role in the improvement of ventricular remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…However, SGLT-2 inhibitors could significantly reduce E/e′ and improve diastolic function of the left ventricle. Some studies suggested that SGLT-2 inhibitors could reduce oxidative stress [66], thereby improving arteriosclerosis and endothelial dysfunction. Experimental data in obese and diabetic mice demonstrated that the SGLT-2 inhibitor empagliflozin significantly ameliorated cardiac fibrosis, coronary arterial thickening, and cardiac macrophage infiltration, suggesting a direct cardiac effect along with an attenuation of oxidative stress on the myocardium [67].…”

Section: Discussionmentioning

confidence: 99%

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Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis

Zhang

Wang

et al. 2020

Cardiovasc Diabetol

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Background: Although a variety of antidiabetic drugs have significant protective action on the cardiovascular system, it is still unclear which antidiabetic drugs can improve ventricular remodeling and fundamentally delay the process of heart failure. The purpose of this network meta-analysis is to compare the efficacy of sodium glucose cotransporter type 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, metformin (MET), sulfonylurea (SU) and thiazolidinediones (TZDs) in improving left ventricular (LV) remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). Methods: We searched articles published before October 18, 2019, regardless of language or data, in 4 electronic databases: PubMed, EMBASE, Cochrane Library and Web of Science. We included randomized controlled trials in this network meta-analysis, as well as a small number of cohort studies. The differences in the mean changes in left ventricular echocardiographic parameters between the treatment group and control group were evaluated. Results: The difference in the mean change in LV ejection fraction (LVEF) between GLP-1 agonists and placebo in treatment effect was greater than zero (MD = 2.04% [0.64%, 3.43%]); similar results were observed for the difference in the mean change in LV end-diastolic diameter (LVEDD) between SGLT-2 inhibitors and placebo (MD = − 3.3 mm [5.31, − 5.29]), the difference in the mean change in LV end-systolic volume (LVESV) between GLP-1 agonists and placebo (MD = − 4.39 ml [− 8.09, − 0.7]); the difference in the mean change in E/e′ between GLP-1 agonists and placebo (MD = − 1.05[− 1.78, − 0.32]); and the difference in the mean change in E/e′ between SGLT-2 inhibitors and placebo (MD = − 1.91[− 3.39, − 0.43]). Conclusions: GLP-1 agonists are more significantly associated with improved LVEF, LVESV and E/e′, SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e′, and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume (LVEDV) than are placebos. SGLT-2 inhibitors are superior to other drugs in pairwise comparisons.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis

Zhang

Wang

et al. 2020

Cardiovasc Diabetol

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“…78 In addition to a glucose-lowering effect, SGLT2 inhibitors exert several cardiorenal and metabolic benefits, including weight loss; therefore, they are thought to be promising therapeutic agents for patients with NAFLD. 79 Although beneficial effects continue to be reported, SGLT2 inhibitors are not yet generally recommended for the treatment of NAFLD.…”

Section: Sodium-glucose Cotransporter 2 (Sglt2) Inhibitorsmentioning

confidence: 99%

Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease

Kim

Lee

2020

Clin Mol Hepatol

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder and is associated with various metabolic diseases, including type 2 diabetes mellitus. There are no approved drugs for NAFLD, and the only approved treatment option is weight reduction. As insulin resistance plays an important role in the development of NAFLD, many anti-diabetic drugs have been evaluated for the treatment of NAFLD. Improvement of liver enzymes has been demonstrated by many anti-diabetic drugs, but histological assessment still remains insufficient. Pioglitazone could become the first-line therapy for T2DM patients with NAFLD, based on evidence of histological improvement in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liraglutide, another promising alternative, is not yet recommended in patients with NAFLD/NASH due to limited evidence. Therefore, well-designed randomized controlled trials should be performed in the near future to demonstrate if and how anti-diabetic drugs can play a role in the treatment of NAFLD.

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“…Nevertheless, warnings about HF risk have been added to the labels of several DPP-4is, including saxagliptin [124], alogliptin [26], and vildagliptin [125]. In contrast, other therapies, particularly GLP-1 receptor agonists (e.g., semaglutide and liraglutide) and SGLT2is (e.g., canagliflozin and empagliflozin), appear to have protective effects against CV disease [126].…”

Section: Risk Evaluationmentioning

confidence: 99%

Benefit-Risk Assessment of Alogliptin for the Treatment of Type 2 Diabetes Mellitus

et al. 2019

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The dipeptidyl peptidase-4 inhibitor (DPP-4i) alogliptin is an oral, antidiabetic treatment that is approved in many countries to treat patients with type 2 diabetes mellitus (T2DM), including the USA, Europe, and Japan. Alogliptin is efficacious both as monotherapy and as add-on/combination therapy with other commonly prescribed T2DM treatments, such as metformin and pioglitazone. Overall, alogliptin is well-tolerated in patients with T2DM, including older patients, those with renal and/or hepatic impairment, and those at high risk of cardiovascular events. There is a low risk of hypoglycemia, weight gain, acute pancreatitis, and gastrointestinal adverse events with alogliptin treatment, as demonstrated in long-term trials (lasting up to 4.5 years) and in a real-world setting. Additionally, alogliptin has a generally favorable or similar safety profile in comparison to other antidiabetic agents (metformin, thiazolidinediones, sulfonylureas, glucagon-like peptide-1 receptor agonists, sodiumglucose cotransporter 2 inhibitors, α-glucosidase inhibitors, and insulin). However, further evaluation would be required to determine the mechanism and effect of alogliptin on heart failure, bullous pemphigoid, and inflammatory bowel disease. Of note, due to the ethnic diversity in the epidemiology of T2DM, alogliptin has been shown to be more efficacious in Asian patients than in non-Asian patients with T2DM, but with a similar tolerability profile. These data indicate that DPP-4is, including alogliptin, are important treatment options, especially for Asian patients with T2DM, for whom they have potential as a first-line therapy. This benefit-risk assessment aims to place alogliptin within the current armamentarium of T2DM and aid physicians when choosing optimal diabetes treatment for their patients.

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The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes

Cited by 15 publications

References 71 publications

Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis

Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis

Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease

Benefit-Risk Assessment of Alogliptin for the Treatment of Type 2 Diabetes Mellitus

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