Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials

Lago, Rodrigo M.; Singh, Premranjan P.; Nesto, Richard W.

doi:10.1016/s0140-6736(07)61514-1

Cited by 652 publications

(451 citation statements)

References 46 publications

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“…This is highlighted in chronic treatments that influence inflammation which may produce untoward consequences as seen with glucocorticoids, COX inhibitors (e.g. rofecoxib/Vioxx) and possibly rosiglitazone (Avandia; Lago et al 2007). …”

Section: Metabolic Control By Nrsmentioning

confidence: 99%

Nuclear receptors, mitochondria and lipid metabolism

2008

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Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome proliferator activated receptors (PPARs) and Liver X receptors (LXRs), acting in concert with PPARγ Coactivator 1α (PGC-1α), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia, and obesity). Recently, additional partners of PGC-1α have moved to the forefront of metabolic research, the Estrogen-related Receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function.

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Section: Metabolic Control By Nrsmentioning

confidence: 99%

Nuclear receptors, mitochondria and lipid metabolism

2008

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“…Peripheral oedema is seen in 5-15% of treated individuals. This side effect just about doubles the risk of congestive heart failure, but does not increase mortality [2]. There is no evidence that the increased risk of heart failure is due to a negative inotropic effect [3,4], thus fluid retention remains the major contributor.…”

Section: Introductionmentioning

confidence: 99%

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

et al. 2010

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Aims/hypothesis Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension. Methods In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension. Results Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the bloodpressure response to salt and abolished salt sensitivity in salt-sensitive individuals. Conclusions/interpretation Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones.

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“…[4][5][6][7] However, various studies indicate that, despite being effective in lowering the glucose and glycated hemoglobin levels, some hypoglycemic medications may increase, rather than reduce, the risk of cardiovascular events. [8][9][10] These unexpected findings prompted the reexamination of the regulatory approval processes for new antidiabetic therapies, which had been based primarily on the surrogate measure of glucose lowering with limited clinical-outcomes data. Since 2008, regulatory agencies have required robust cardiovascular-outcome data from randomized, controlled trials in order to grant and sustain approvals of drugs or biologic agents for the treatment or prevention of diabetes mellitus.…”

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confidence: 99%

Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome

et al. 2015

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BACKGROUND: Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event. METHODS: We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina. RESULTS: The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo. CONCLUSIONS: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.). Jean-Claude (2015). Lixisenatide in patients with type 2 diabetes and acute coronary syndrome.

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Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials

Cited by 652 publications

References 46 publications

Nuclear receptors, mitochondria and lipid metabolism

Nuclear receptors, mitochondria and lipid metabolism

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome

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