Dataset Information

Spotlight on Antidiabetic Agents with Cardiovascular or Renoprotective Benefits.

ABSTRACT: Type 2 diabetes mellitus often goes hand in hand with cardiovascular and renal comorbidities. Stroke, myocardial infarction, heart failure, and chronic kidney disease are high-risk complications of type 2 diabetes that contribute to morbidity and mortality. Recent clinical trials have uncovered evidence that certain antidiabetic agents may confer cardiovascular and/or renal benefits such as reduced cardiovascular and all-cause mortality and reduced need for renal replacement therapy. Two landmark trials in particular, EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) and LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results), demonstrated the cardioprotective and/or renoprotective effects of empagliflozin and liraglutide, respectively. These trials led to new US Food and Drug Administration indications for empagliflozin and liraglutide as risk reduction for major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease. Other trials are under way to determine whether these benefits are class effects and what other agents may have a role in risk reduction for cardiovascular and renal disease. This review will summarize the evidence for noninsulin antidiabetic drugs with benefits beyond glycemic control, discuss proposed mechanisms for these effects, and consider their place in therapy.

SUBMITTER: Madievsky R

PROVIDER: S-EPMC6141654 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Spotlight on Antidiabetic Agents with Cardiovascular or Renoprotective Benefits.

Madievsky Ruth R

The Permanente journal 20180101

Type 2 diabetes mellitus often goes hand in hand with cardiovascular and renal comorbidities. Stroke, myocardial infarction, heart failure, and chronic kidney disease are high-risk complications of type 2 diabetes that contribute to morbidity and mortality. Recent clinical trials have uncovered evidence that certain antidiabetic agents may confer cardiovascular and/or renal benefits such as reduced cardiovascular and all-cause mortality and reduced need for renal replacement therapy. Two landmar ...[more]

PMID: 30227909

Similar Datasets

Project description:ObjectiveTo review the literature on the association between antidiabetic agents and morbidity and mortality in people with heart failure and diabetes.DesignSystematic review and meta-analysis of controlled studies (randomised trials or cohort studies) evaluating antidiabetic agents and outcomes (death and admission to hospital) in patients with heart failure and diabetes.Data sourcesElectronic databases, manual reference search, and contact with investigators.Review methodsTwo reviewers independently extracted data. Risk estimates for specific treatments were abstracted and pooled estimates derived by meta-analysis where appropriate.ResultsEight studies were included. Three of four studies found that insulin use was associated with increased risk for all cause mortality (odds ratio 1.25, 95% confidence interval 1.03 to 1.51; 3.42, 1.40 to 8.37 in studies that did not adjust for diet and antidiabetic drugs; hazard ratio 1.66, 1.20 to 2.31; 0.96, 0.88 to 1.05 in the studies that did). Metformin was associated with significantly reduced all cause mortality in two studies (hazard ratio 0.86, 0.78 to 0.97) compared with other antidiabetic drugs and insulin; 0.70, 0.54 to 0.91 compared with sulfonylureas); a similar trend was seen in a third. Metformin was not associated with increased hospital admission for any cause or for heart failure specifically. In four studies, use of thiazolidinediones was associated with reduced all cause mortality (pooled odds ratio 0.83, 0.71 to 0.97, I2=52%, P=0.02). Thiazolidinediones were associated with increased risk of hospital admission for heart failure (pooled odds ratio 1.13 (1.04 to 1.22), I2=0%, P=0.004). The two studies of sulfonylureas had conflicting results, probably because of differences in comparator treatments. Important limitations were noted in all studies.ConclusionMetformin was the only antidiabetic agent not associated with harm in patients with heart failure and diabetes. It was associated with reduced all cause mortality in two of the three studies.

Project description:IntroductionCardiovascular benefits observed with new antidiabetic agents may not extend to chronic kidney disease (CKD) patients. This study performed a systematic review and meta-analysis of cardiovascular outcome trials (CVOTs) using new antidiabetic agents stratified by kidney function.MethodsMEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials were searched for eligible studies up to November 16, 2020. Data were stratified by the trial entry estimated glomerular filtration rate (eGFR) and albuminuria. Primary major cardiovascular event (MACE) outcomes were extracted, and a meta-analysis with a random effects model was performed to estimate overall risk ratios (RRs).ResultsOur search identified 16 studies for inclusion (glucagon-like peptide-1 [GLP-1] analogues, n = 6; dipeptidyl-peptidase 4 [DPP-4] inhibitors, n = 4; and sodium-glucose cotransporter-2 [SGLT-2] inhibitors, n = 6) with a combined total of 150,816 participants (28.2% with eGFR <60 ml/min per 1.73 m2, n = 42,534). The RR for MACE with GLP-1 analogues with an eGFR ≥60 ml/min per 1.73 m2 was 0.87 (95% confidence interval [CI], 0.77-0.98; P = 0.02) and 0.90 (95% CI, 0.78-1.04; P = 0.14) with an eGFR <60 ml/min per 1.73 m2. The RR for MACE with DPP-4 inhibitors with eGFR ≥60 ml/min per 1.73 m2 was 0.99 (95% CI, 0.92-1.07; P = 0.86) and 0.99 (95% CI, 0.91-1.08; P = 0.86) with an eGFR <60 ml/min per 1.73 m2. The RR for MACE with SGLT-2 inhibitors with an eGFR ≥60 ml/min per 1.73 m2 was 1.01 (95% CI, 0.92-1.10; P = 0.87) and 0.85 (95% CI, 0.75-0.95; P = 0.005) with an eGFR <60 ml/min per 1.73 m2. Most analyses had significant heterogeneity. Sufficient albuminuria data were unavailable to analyze empirically.ConclusionClear evidence for MACE prevention in diabetes patients with an eGFR <60 ml/min per 1.73 m2 currently exists for SGLT-2 inhibitors only. However, similar GLP-1 analogue effect sizes suggest a lack of sufficient power rather than a lack of effect.

Project description:Diabetic kidney disease represents a considerable burden; around one-third of patients with type 2 diabetes develop chronic kidney disease. In health, the kidneys play an important role in the regulation of glucose homeostasis via glucose utilization, gluconeogenesis and glucose reabsorption. In patients with diabetes, renal glucose homeostasis is significantly altered with an increase in both gluconeogenesis and renal tubular reabsorption of glucose. Environmental factors, both metabolic (hyperglycaemia, obesity and dyslipidaemia) and haemodynamic, together with a genetic susceptibility, lead to the activation of pro-oxidative, pro-inflammatory and pro-fibrotic pathways resulting in kidney damage. Hyperfiltration and its haemodynamic-driven insult to the kidney glomeruli is an important player in proteinuria and progression of kidney disease towards end-stage renal failure. Control of glycaemia and blood pressure are the mainstays to prevent kidney damage and slow its progression. There is emerging evidence that some hypoglycaemic agents may have renoprotective effects which are independent of their glucose-lowering effects. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors may exert a renoprotective effect by a number of mechanisms including restoring the tubuloglomerular feedback mechanism and lowering glomerular hyperfiltration, reducing inflammatory and fibrotic markers induced by hyperglycaemia thus limiting renal damage. Simultaneous use of an SGLT-2 inhibitor and blockade of the renin-angiotensin-aldosterone system may be a strategy to slow progression of diabetic nephropathy more than either drug alone. The use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists may exert a renoprotective effect by reducing inflammation, fibrosis and blood pressure. Given the burden of diabetic kidney disease, any additional renoprotective benefit with hypoglycaemic therapy is to be welcomed. Large randomized controlled trials are currently underway investigating if these new anti-diabetic agents can provide renoprotection in diabetes.

Dataset Information

Spotlight on Antidiabetic Agents with Cardiovascular or Renoprotective Benefits.

Publications

Spotlight on Antidiabetic Agents with Cardiovascular or Renoprotective Benefits.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets