Key result
Sodium-glucose co-transporter-2 inhibitors demonstrate beneficial effects on heart failure in diabetic patients, whereas thiazolidinediones and certain dipeptidyl peptidase-4 inhibitors increase risk.
Why the study?
Diabetic patients have an increased risk of heart failure, and the co-existence of diabetes and heart failure is associated with poor prognosis.
How do various anti-diabetic therapies affect the risk and outcomes of heart failure in diabetic patients?
How do various anti-diabetic therapies affect the risk and outcomes of heart failure in diabetic patients?
This review highlights the divergent effects of anti-diabetic therapies on heart failure, emphasizing the benefits of SGLT2 inhibitors and the potential harm of thiazolidinediones and specific DPP-4 inhibitors.
May support SGLT2i in diabetic HF; leaves open mechanisms in Level 5 data.
Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin-angiotensin II-aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.
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Hsu et al. (2023) conducted a review in Diabetes and Heart Failure. Anti-diabetic therapies was evaluated. Sodium-glucose co-transporter-2 inhibitors demonstrate beneficial effects on heart failure in diabetic patients, whereas thiazolidinediones and certain dipeptidyl peptidase-4 inhibitors increase risk.
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