The effects of antidiabetic agents on heart failure

Wijnen, Mark; Duschek, Erik J J; Boom, Henk; Vliet, Martin van

doi:10.1007/s12471-021-01579-2

Cited by 5 publications

(3 citation statements)

References 59 publications

(80 reference statements)

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“…Although, recent large randomized controlled trials have not shown differences in cardiovascular risk of sulfonylureas versus pioglitazone or linagliptin [70]. Some studies point to a higher incidence of DHF in patients with T2DM taking sulfonylureas; others show inconclusive data [71].…”

Section: Patients' Pharmacotherapeutic Profile and Acute Cardiovascul...mentioning

confidence: 99%

Clinical and Pharmacotherapeutic Profile of Patients with Type 2 Diabetes Mellitus Admitted to a Hospital Emergency Department

et al. 2023

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Type 2 diabetes mellitus (T2DM) is closely associated with other pathologies, which may require complex therapeutic approaches. We aim to characterize the clinical and pharmacological profile of T2DM patients admitted to an emergency department. Patients aged ≥65 years and who were already using at least one antidiabetic drug were included in this analysis. Blood glycemia, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemoglobin were analyzed for each patient, as well as personal pathological history, diagnosis(s) at admission, and antidiabetic drugs used before. Outcome variables were analyzed using Pearson’s Chi-Square, Fisher’s exact test, and linear regression test. In total, 420 patients were randomly selected (48.6% male and 51.4% female). Patients with family support showed a lower incidence of high glycemia at admission (p = 0.016). Higher blood creatinine levels were associated with higher blood glycemia (p = 0.005), and hyperuricemia (HU) (p = 0.001), as well as HU, was associated with a higher incidence of acute cardiovascular diseases (ACD) (p = 0.007). Hemoglobin levels are lower with age (p = 0.0001), creatinine (p = 0.009), and female gender (p = 0.03). The lower the AST/ALT ratio, the higher the glycemia at admission (p < 0.0001). Obese patients with (p = 0.021) or without (p = 0.027) concomitant dyslipidemia had a higher incidence of ACD. Insulin (p = 0.003) and glucagon-like peptide-1 agonists (GLP1 RA) (p = 0.023) were associated with a higher incidence of decompensated heart failure, while sulfonylureas (p = 0.009), metformin-associated with dipeptidyl peptidase-4 inhibitors (DPP4i) (p = 0.029) or to a sulfonylurea (p = 0.003) with a lower incidence. Metformin, in monotherapy or associated with DPP4i, was associated with a lower incidence of acute kidney injury (p = 0.017) or acute chronic kidney injury (p = 0.014). SGLT2i monotherapy (p = 0.0003), associated with metformin (p = 0.026) or with DPP4i (p = 0.007), as well as insulin and sulfonylurea association (p = 0.026), were associated with hydroelectrolytic disorders, unlike GLP1 RA (p = 0.017), DPP4i associated with insulin (p = 0.034) or with a GLP1 RA (p = 0.003). Insulin was mainly used by autonomous and institutionalized patients (p = 0.0008), while metformin (p = 0.003) and GLP1 RA (p < 0.0001) were used by autonomous patients. Sulfonylureas were mostly used by male patients (p = 0.027), while SGLT2 (p = 0.0004) and GLP1 RA (p < 0.0001) were mostly used by patients within the age group 65–85 years. Sulfonylureas (p = 0.008), insulin associated with metformin (p = 0.040) or with a sulfonylurea (p = 0.048), as well as DPP4i and sulfonylurea association (p = 0.031), were associated with higher blood glycemia. T2DM patients are characterized by great heterogeneity from a clinical point of view presenting with several associated comorbidities, so the pharmacotherapeutic approach must consider all aspects that may affect disease progression.

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Section: Patients' Pharmacotherapeutic Profile and Acute Cardiovascul...mentioning

confidence: 99%

Clinical and Pharmacotherapeutic Profile of Patients with Type 2 Diabetes Mellitus Admitted to a Hospital Emergency Department

et al. 2023

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“…Indeed, the insulin resistance observed in obese diabetic subjects directly impacts metabolic health through reduced systemic glucose clearance and progressive loss of lean muscle mass [2; 3]. Recent successes in glycemic control through antihyperglycemic drugs are positively impacting the management heart failure risk [4; 5]. However, muscle-centered mechanisms to rescue lean mass and strength in conditions of insulin resistance remain very limitedly elucidated.…”

Section: Introductionmentioning

confidence: 99%

The human genetic variant rs6190 unveils Foxc1 and Arid5a as novel pro-metabolic targets of the glucocorticoid receptor in muscle.

Prabakaran,

Chung,

McFarland

et al. 2024

Preprint

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Genetic variations in the glucocorticoid receptor (GR) gene NR3C1 can impact metabolism. The single nucleotide polymorphism (SNP) rs6190 (p.R23K) has been associated in humans with enhanced metabolic health, but the SNP mechanism of action remains completely unknown. We generated a transgenic knock-in mice genocopying this polymorphism to elucidate how the mutant GR impacts metabolism. Compared to non-mutant littermates, mutant mice showed increased muscle insulin sensitivity and strength on regular chow and high-fat diet, blunting the diet-induced adverse effects on weight gain and exercise intolerance. Overlay of RNA-seq and ChIP-seq profiling in skeletal muscle revealed increased transactivation of Foxc1 and Arid5A genes by the mutant GR. Using adeno-associated viruses for in vivo overexpression in muscle, we found that Foxc1 was sufficient to transcriptionally activate the insulin response pathway genes Insr and Irs1. In parallel, Arid5a was sufficient to transcriptionally repress the lipid uptake genes Cd36 and Fabp4, reducing muscle triacylglycerol accumulation. Collectively, our findings identify a muscle-autonomous epigenetic mechanism of action for the rs6190 SNP effect on metabolic homeostasis, while leveraging a human nuclear receptor coding variant to unveil Foxc1 and Arid5a as novel epigenetic regulators of muscle metabolism.

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“…These trials mainly focus on 3-point major adverse cardiovascular events (3P-MACE) including CV death, nonfatal stroke, and nonfatal myocardial infarction (MI), with some including unstable angina (4P-MACE). In recent years, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have emerged as newer classes of antidiabetic agents, undergoing extensive testing for their CV effects and demonstrating promising outcomes in reducing CV risks among individuals with T2DM [ 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Hypoglycemic Drugs in Patients with Diabetes Mellitus and Heart Failure: A Narrative Review

Nikolaidou,

Ventoulis,

Karakoulidis

et al. 2024

Medicina

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Over the last few years, given the increase in the incidence and prevalence of both type 2 diabetes mellitus (T2DM) and heart failure (HF), it became crucial to develop guidelines for the optimal preventive and treatment strategies for individuals facing these coexisting conditions. In patients aged over 65, HF hospitalization stands out as the predominant reason for hospital admissions, with their prognosis being associated with the presence or absence of T2DM. Historically, certain classes of glucose-lowering drugs, such as thiazolidinediones (rosiglitazone), raised concerns due to an observed increased risk of myocardial infarction (MI) and cardiovascular (CV)-related mortality. In response to these concerns, regulatory agencies started requiring CV outcome trials for all novel antidiabetic agents [i.e., dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is)] with the aim to assess the CV safety of these drugs beyond glycemic control. This narrative review aims to address the current knowledge about the impact of glucose-lowering agents used in T2DM on HF prevention, prognosis, and outcome.

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The effects of antidiabetic agents on heart failure

Cited by 5 publications

References 59 publications

Clinical and Pharmacotherapeutic Profile of Patients with Type 2 Diabetes Mellitus Admitted to a Hospital Emergency Department

Clinical and Pharmacotherapeutic Profile of Patients with Type 2 Diabetes Mellitus Admitted to a Hospital Emergency Department

The human genetic variant rs6190 unveils Foxc1 and Arid5a as novel pro-metabolic targets of the glucocorticoid receptor in muscle.

Hypoglycemic Drugs in Patients with Diabetes Mellitus and Heart Failure: A Narrative Review

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