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SGLT2-Is is recommended in all patients with HF and T2DM, independently of glycated haemoglobin levels or other concomitant glucose-lowering agents. SGLT2-Is are generally well tolerated, although they may cause urinary infections and genital fungal infections as vulvovaginitis and balanitis with a prevalence of up to 6.9% in women and 4.8% in men. They are not indicated in patients with type 1 diabetes mellitus due to the risk of diabetic ketoacidosis (reported incidence of 2%– 3%).835,836 Semaglutide or tirzepatide should be added if not contraindicated in patients with HFpEF and T2DM, especially if they are also obese.316,317 Metformin, despite its long history as first-line treatment of T2DM, has no dedicated CV outcome trials to assess its safety or efficacy; observational studies reported a lower risk of death or HFH in patients with HF when compared with insulin and sulfonylureas.837–839 Metformin is not recommended in patients with an eGFR <30 mL/min/1.73 m2 or hepatic impairment because of the risk of lactic acidosis. In the context of T2DM, insulin glargine and insulin degludec have been evaluated in specific CV outcome trials, demonstrating a neutral effect on incident HF in patients with diabetes.840–842 In post-hoc analyses of RCTs and retrospective registries, use of insulin was associated with poorer outcomes among patients with HF. Thus, if insulin is needed in a patient with HF, patients should be monitored for WHF after initiation of treatment.843,844 The dipeptidyl peptidase-4 inhibitor saxagliptin and thiazolidinediones (glitazones) have been associated with an approximately 30% increased risk of HFH and, thus, are contraindicated in patients with HF.845,846 No consistent data are available for the use of sulphonylureas in patients with HF.60

10.3 Chronic kidney disease

Chronic kidney disease and HF frequently coexist.847 They share common risk factors and may develop simultaneously. CKD may lead to worsening of cardiac function and vice versa. The incidence of CKD is five-fold higher in patients with HF as compared with those without.848 About 30%–40% of individuals with chronic HF have CKD, with the highest proportions, up to 50%, in HFpEF.778,849,850 CKD is a major independent determinant of increased mortality and morbidity in HF.850 Albuminuria and low GFR are independently associated with an increased risk of major ASCVD, HF events, and CV death.61,851–854 The presence of CKD might have an impact on FMT optimization, and it is often cited as a reason for FMT under-utilization in clinical practice.855 Even in most patients with CKD the initiation of beta-blockers, ACE-Is/ARNIs/ARBs, SGLT2-Is, and MRAs is recommended.164 Several RCTs have shown that patients with HF and concomitant CKD are at higher risk of events as compared to those without CKD. However, no interaction between drug effects and kidney function was noted in subgroup analyses of these trials.242–245,309 Furthermore, the beneficial effects of FMT are similar, or even higher, irrespective of CKD.251,252,847,856–858 An evidence gap remains for the treatment of HF in patients with severe CKD as these patients were generally excluded from RCTs. Worsening kidney function in patients with chronic HF is not necessarily associated with worse outcomes. For example, after initiation of ACE-Is/ARNIs/ARBs, MRAs or SGLT2-Is, an initial decrease in the glomerular filtration pressure may decrease GFR and increase serum creatinine. These changes are generally transient and occur despite improvement in patient outcomes and may delay long term deterioration of kidney function.243,250–253 Sacubitril–valsartan, compared with enalapril, led to a slower decline in kidney function, despite a slight increase in the UACR, and improved CV outcomes to a similar extent in patients with CKD vs other patients in the PARADIGM-HF trial.279 In a participant-level pooled analysis of the DAPA-HF and DELIVER trials, patients experiencing worsening of eGFR to <25 mL/min/1.73 m2 were at heightened risk for development of subsequent CV events. Continuation of dapagliflozin was associated with lower rates of the primary composite outcome.859

A prespecified secondary analysis of the FINEARTS-HF trial, in patients with HF and LVEF ≥40%, reported an acute decline in eGFR of −2.9 mL/min/1.73 m2 (95% CI −3.4 to −2.4) during the first 3 months on finerenone vs placebo.860 However, finerenone still reduced the risk of new-onset micro- and macroalbuminuria by 24% and 38%, respectively.860 Thus, a transient decrease in kidney function after the initiation of ACE-Is/ARNIs/ARBs and MRAs or SGLT2-Is should not prompt their interruption. An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/ min/1.73 m2, is considered acceptable. Notably, in patients with HFpEF, semaglutide and tirzepatide may acutely reduce eGFR; however, they exhibit a long-term protective effect on kidney function.861,862 Chronic kidney disease is highly prevalent in patients with DHF. Worsening or improvement of kidney function occurs commonly, affecting about 30%–50% of patients admitted with HF.273 Adverse CV outcomes are observed in patients with worsening kidney function and poor diuretic response, but not in patients with good diuretic response.506,863 Data from the STRONG-HF trial showed that a decrease in eGFR within 1 week after discharge was associated with more evidence of congestion and with an increased incidence of HF readmissions.864 Conversely, worsening kidney function is not associated with poor outcomes in the context of successful decongestion.506,863 For further details refer to the 2026 ESC Guidelines on cardiovascular disease and chronic kidney disease.122

10.4 Iron deficiency and anaemia

Iron deficiency and anaemia are common in patients with HF and are associated with reduced functional capacity, and worse QoL and prognosis independently of each other.778,865–868 Iron deficiency is slightly more prevalent in patients with HFpEF than in patients with HFrEF.865,869 In patients with HF, ID has been defined as either ferritin <100 ng/mL, or ferritin 100–299 ng/mL with TSAT <20%. This definition has been adopted by the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure3 and the 2023 Focused Update of the 2021 ESC Guidelines for the Downloaded from academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehag100/8766302 by guest on 31 August 2026