Type 2 diabetes and decompensated heart failure on pioglitazone — case discussion

Presentation

Practice case (not a real patient). A 67-year-old man with type 2 diabetes is admitted with decompensated heart failure. His LVEF is 35%. Before admission he took metformin and pioglitazone. On admission his eGFR is 48 mL/min/1.73 m² and his UACR is 20 mg/g.^[1][4] After initial stabilisation with diuretics, the team reviews his glucose-lowering drugs.^[4]

Step 1 — What has to stop?

Discussion:

• Pioglitazone: ESC 2023 says it is associated with an increased risk of incident HF in patients with diabetes and is not recommended for glucose-lowering treatment in patients at risk of HF (or with previous HF) (Class III, Level A).^[1]
• ESC 2023 reports that thiazolidinediones increased the risk of HF hospitalisation in several trials and are not recommended in patients with diabetes and symptomatic HF; ADA 2026 says they should be avoided in people with heart failure.^[1][2]
• Metformin: ADA 2026 (10.45, grade B) says it should be avoided in unstable or hospitalised individuals with heart failure, and may be continued in stable heart failure if eGFR remains >30 mL/min/1.73 m².^[2]

Step 2 — Which glucose-lowering drug should start?

• ESC 2026 HF: in-hospital initiation of an SGLT2 inhibitor is recommended in patients with decompensated HF after initial stabilisation, to improve QoL and congestion symptoms and reduce the risk of HF hospitalisation (Class I, Level B1).^[4]
• ESC 2026 HF: an SGLT2 inhibitor (dapagliflozin or empagliflozin) is recommended in patients with symptomatic HF independent of LVEF to reduce the risk of HF hospitalisation or CV death (Class I, Level A).^[4]
• ESC 2026 HF adds that the use of SGLT2 inhibitors is recommended in all patients with HF and T2DM, independently of glycated haemoglobin levels or other concomitant glucose-lowering agents.^[4]
• His eGFR of 48 mL/min/1.73 m² is a single admission value; ESC 2023 says a persistent decrease in eGFR <60 mL/min/1.73 m² is sufficient to confirm CKD, and if CKD is confirmed, the ESC 2023 row recommending an SGLT2 inhibitor (canagliflozin, empagliflozin or dapagliflozin) in T2DM and CKD with an eGFR ≥20 mL/min/1.73 m² to reduce the risk of CVD and kidney failure (Class I, Level A) also applies.^[1]
• ADA 2026 (10.41a, grade A): in type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor (including SGLT1/2 inhibitor) with proven benefit in this population is recommended to reduce the risk of worsening heart failure and cardiovascular death.^[2]
• ADA 2026 (10.41b, grade A): in the same patients, an SGLT2 inhibitor with proven benefit in this population is recommended to improve quality of life.^[2]
• CKM 2026 (stage 4 with T2D and HF; COR 1, LOE A): SGLT2i should be prioritized as the first-line cardioprotective glucose-lowering medications to reduce cardiovascular death and HF hospitalizations.^[3]
• ADA 2026 (10.44g, grade A): in individuals with diabetes, guideline-directed medical therapy for myocardial infarction and symptomatic stage C heart failure is recommended with ACE inhibitors or ARBs (including ARBs and neprilysin inhibitors), MRAs, β-blockers and SGLT2 inhibitors.^[2]

Step 3 — If more glucose control is needed after discharge

• ESC 2023, for when additional glucose control is needed: the listed GLP-1 RAs (lixisenatide, liraglutide, semaglutide, exenatide ER, dulaglutide, efpeglenatide), and the DPP-4 inhibitors sitagliptin and linagliptin, have a neutral effect on the risk of HF hospitalisation and should be considered for glucose-lowering treatment in T2DM at risk of or with HF (Class IIa, Level A).^[1]
• ESC 2023, for when additional glucose control is needed: metformin should be considered for glucose-lowering treatment in T2DM and HF, in chronic and stable HF (Class IIa, Level B); ESC 2026 HF says metformin is not recommended at eGFR <30 mL/min/1.73 m² or with hepatic impairment because of the risk of lactic acidosis.^[1][4]
• Saxagliptin is not an alternative: ESC 2023 does not recommend it for glucose-lowering treatment in patients at risk of HF (or with previous HF) (Class III, Level B).^[1]
• ESC 2023, for when additional glucose control is needed: basal insulins (glargine and degludec) have a neutral effect on the risk of HF hospitalisation and should be considered for glucose-lowering treatment in T2DM at risk of or with HF (Class IIa, Level B).^[1]
• ESC 2023 Figure 16 adds that a GLP-1 RA is preferred in patients with ASCVD and if weight reduction is needed, and is not to be combined with a DPP-4 inhibitor.^[1]
• ESC 2026 HF: if insulin is needed in a patient with HF, the patient should be monitored for worsening HF after it is started.^[4]

Step 4 — Safety counselling

• ESC 2026 HF: SGLT2 inhibitors are generally well tolerated but may cause urinary infections and genital fungal infections, with a prevalence of up to 4.8% in men.^[4]
• ADA 2026 (10.46, grade E): educate individuals with diabetes at risk of diabetic ketoacidosis who are treated with SGLT inhibition on the risks and signs of ketoacidosis and methods of risk mitigation management, provide them with appropriate tools for ketone measurement (serum β-hydroxybutyrate) and discourage a ketogenic eating pattern.^[2]