DPP4 inhibitors and cardiovascular outcomes: safety on heart failure

Xia, Chang; Goud, Aditya; D’Souza, Jason; Dahagam, Chanukya H.; Rao, Xiaoquan; Rajagopalan, Sanjay; Zhong, Jixin

doi:10.1007/s10741-017-9617-4

Cited by 24 publications

(16 citation statements)

References 50 publications

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“…There is also a direct effect on calcium transport and lipid metabolism, leading to diabetic cardiomyopathy. Sympathetic over-expression in heart failure is responsible for increased insulin resistance, reduces insulin secretion and stimulates glucagon release, which induces hepatic gluconeogenesis (6).…”

Section: Mechanism Of Action Of Glp-1 Hormone and Its Pleiotropic Effmentioning

confidence: 99%

Metabolic and cardiovascular benefits of GLP‑1 agonists, besides the hypoglycemic effect (Review)

et al. 2020

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Patients with type 2 diabetes exhibit higher cardiovascular risk than normal individuals. Optimal blood glucose levels are rarely achieved in diabetic patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a new antidiabetic drug class with multiple metabolic effects. Some trials have evaluated their safety, but it has been recently demonstrated that this new class has cardiovascular benefits, through other mechanisms than glycemic control. The use of GLP-1RAs was associated with a significant reduction of cardiovascular and all-cause mortality, with a safe profile related to pancreatitis or thyroid cancer, as compared with placebo. This review presents the cardiovascular and metabolic benefits of GLP-1 RAs versus placebo, in patients with type 2 diabetes. Semaglutide and liraglutide demonstrated a reduction in cardiovascular events, with similar rates on cardiovascular mortality. Ongoing trials assess the cardiovascular benefits and side effects of dulaglutide treatment. Exenatide and liraglutide demonstrated the decrease of blood pressure values, weight reduction and improvement of dyslipidemia. Liraglutide induced, both in vivo and in vitro, an improvement of blood circulation, increasing the nitric oxide level and inhibiting the adhesion and procoagulant factors. Also, liraglutide demonstrated beneficial effects on cardiac remodeling after myocardial infarction, but more large trials are required. However, the international guidelines recommend using GLP-1 RAs as first-line therapy in type 2 diabetes patients with high cardiovascular risk or as first-line agents in patients intolerant to metformin. Contents 1. Introduction 2. Mechanism of action of GLP-1 hormone and its pleiotropic effects 3. Evidence of cardiovascular effects of GLP-1 agonists 4. Evidence of GLP-1 agonists on metabolism 5. Conclusions

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Section: Mechanism Of Action Of Glp-1 Hormone and Its Pleiotropic Effmentioning

confidence: 99%

Metabolic and cardiovascular benefits of GLP‑1 agonists, besides the hypoglycemic effect (Review)

et al. 2020

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“…The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial [8], the Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care (EXAMINE) [9] trial, and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) [10] demonstrated that, compared with placebo, the addition of saxagliptin, alogliptin and sitagliptin, respectively, neither increased nor decreased the event rate for the primary composite endpoint ( baseline risk for CV events. In SAVOR-TIMI 53 [8], the addition of saxagliptin to existing therapy had a neutral effect on individual components of the primary composite endpoint versus placebo; however, this treatment was associated with a significantly increased risk of HF-related hospital admissions.Consequently, the effect of DPP-4 inhibitors on HF risk in patients with T2DM has been further evaluated in patients with T2DM, and trials of alogliptin, sitagliptin, and vildagliptin did not demonstrate similar results [11]. CVOTs have also been conducted with the selective DPP-4 inhibitor, linagliptin, to further examine its efficacy and safety in high-risk populations.…”

Section: History Of Conditionmentioning

confidence: 99%

Linagliptin in patients with type 2 diabetes and cardiovascular and/or renal disease: results from a cardiovascular and renal outcomes trial

Guthrie

2020

Postgraduate Medicine

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Review of:Rosenstock J, Perkovic V, Johansen, OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321:69-79.McGuire DK, Alexander JH, Johansen OE, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139:351-361.These two papers describe the findings from the CARMELINA trial (Cardiovascular and Renal Microvascular Outcome Study with Linagliptin): the first paper reported results for the primary cardiovascular composite outcome (cardiovascular [CV] death, nonfatal myocardial infarction [MI], or nonfatal stroke; 3-point major adverse cardiovascular event [3P-MACE]) and the key secondary renal composite outcome (renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline); the second paper reported secondary analyses of heart failure (HF) and related outcomes. The CARMELINA trial was a randomized, placebo-controlled, multicenter non-inferiority trial of adults with type 2 diabetes mellitus (T2DM) and elevated CV and renal risk. After a median 2.2-year follow-up of 6979 participants, patients allocated to linagliptin demonstrated no increase in the risk of 3P-MACE versus placebo: hazard ratio (HR) 1.02 [95% confidence interval (CI) 0.89-1.17]; P < 0.001 for non-inferiority. There was also no increase in the risk of hospitalization for HF for linagliptin versus placebo (HR 0.90 [0.74-1.08]). There was no increased risk of progression to end-stage kidney disease or death due to kidney disease (HR 0.87 [0.69-1.10]). Additionally, progression of albuminuria occurred less frequently in patients who received linagliptin versus placebo ). Overall, no new safety findings were identified for linagliptin, and no increased risk of hypoglycemia was observed for linagliptin versus placebo. Together, these findings from the CARMELINA trial reaffirm treatment guidelines for choosing additional therapies for patients with T2DM at elevated CV and/or renal risk, and provide new information on the role of linagliptin in the management of T2DM. ARTICLE HISTORY

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“…Dipeptidyl peptidase-4 (DPP-4) inhibition is a promising oral treatment for T2D either as monotherapy or in combination with other antidiabetic agents. 10,11 This inhibition results in increased insulin secretion and reduced glucagon production by preventing the inactivation of glucose-dependent insulinotropic polypeptide glucagon-like peptide-1 (GLP-1), the two main incretin hormones. 12 Numerous clinical studies have demonstrated that incretin-based therapies are superior to traditional oral hypoglycaemic agents in terms of clinical efficacy and tolerability.…”

Section: Introductionmentioning

confidence: 99%

Saxagliptin and vildagliptin lowered albuminuria in patients with diabetes and hypertension independent on glycaemic control

et al. 2020

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Background Preclinical data illustrated that the dipeptidyl peptidase‐4(DPP‐4) inhibitors did lower urinary albumin excretion in diabetes‐induced rats. We evaluated the effects of saxagliptin and vildagliptin on albuminuria in patients with diabetic nephropathy on top of the renin‐angiotensin‐aldosterone system (RAAS) blockade therapy. Methods This study included 120 patients with type 2 diabetes (T2D), hypertension, and prevalent albuminuria [defined as urine albumin‐to‐creatinine ratio (UACR) 30‐3000mg/g creatinine] on a stable dose of olmesartan as a standard RAAS blocker for diabetic nephropathy. Patients were assigned to receive either of saxagliptin 5mg/day (n = 40), vildagliptin 100mg/day (n = 40), or traditional antidiabetic therapy as control patients (n = 40) for 12 weeks. Results Each of saxagliptin and vildagliptin significantly reduced albuminuria after 12 weeks, with mean percentage changes (%) of −57.9% [95% confidence interval (CI) −66.1 to −49.8], and −55.2% (95% CI −64.9 to −45.4); P < .001, respectively, compared with the control group. Significantly, saxagliptin shifted higher proportions of patients towards lower albuminuria categories (P < .001) compared with vildagliptin despite a similar UACR rate of changes. Results of binary logistic models confirmed that the change in UACR because saxagliptin was independent of changes in systolic blood pressure (SBP), glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), or body weight (overall regression: P = .002, R2 = 0.398) vs control. Likewise, vildagliptin reduced UACR independently on other confounders (overall regression: P = .002, R2 = 0.388). Furthermore, no significant correlation was observed between the change in UACR and changes in HbA1c, SBP or eGFR with either saxagliptin or vildagliptin (Pearson coefficients: 0.203, 0.143, −0.190; P > .05, and 0.003, 0.241, 0.019; P > .05, respectively). Conclusions DPP‐4 inhibitors, saxagliptin, and vildagliptin, resulted in substantial reductions in albuminuria in patients with T2D and hypertension on top of RAAS blockade after short term therapy independently on glycaemic or hemodynamic changes. Saxagliptin was superior to vildagliptin in albuminuria‐categorical shifting.

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DPP4 inhibitors and cardiovascular outcomes: safety on heart failure

Cited by 24 publications

References 50 publications

Metabolic and cardiovascular benefits of GLP‑1 agonists, besides the hypoglycemic effect (Review)

Metabolic and cardiovascular benefits of GLP‑1 agonists, besides the hypoglycemic effect (Review)

Linagliptin in patients with type 2 diabetes and cardiovascular and/or renal disease: results from a cardiovascular and renal outcomes trial

Saxagliptin and vildagliptin lowered albuminuria in patients with diabetes and hypertension independent on glycaemic control

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