Diabetes as cardiovascular disease — viva

Stem

Practice viva. The examiner asks why a cardiologist should care which glucose-lowering drug a patient with type 2 diabetes takes, and works through risk stratification, the SGLT2 inhibitor and GLP-1 RA rows by population, the drug-specific heart failure rows and the outcome trials.^[1]

Branch A — Why is diabetes a cardiovascular problem?

Examiner: Why does a cardiologist own this decision?^[1]

Strong answer:

• ESC 2023: people with T2DM are at a two- to four-fold higher risk of developing CVD during their lifetime, including CAD, stroke, HF, AF and peripheral artery disease, and many patients with CVD have undiagnosed T2DM.^[1]
• ESC 2023 separates two intentions for a glucose-lowering drug: to improve CV outcomes and safety, and to control glucose.^[1]
• Many decisions are independent of glucose management, so T2DM status can inform clinical decision-making for mitigating CV risk.^[1]

Branch B — Risk stratification

Examiner: How do you stratify a patient with type 2 diabetes in Europe?^[1]

Strong answer:

• ESC 2023 recommends screening patients with diabetes for severe TOD (Class I, Level A) and assessing medical history and symptoms suggestive of ASCVD (Class I, Level B).^[1]
• Very high CV risk under ESC 2023 Table 7: clinically established ASCVD, severe TOD or a SCORE2-Diabetes 10-year CVD risk ≥20%.^[1]
• Otherwise, ESC 2023 recommends estimating 10-year CVD risk via SCORE2-Diabetes in T2DM without symptomatic ASCVD or severe TOD (Class I, Level B), in patients aged ≥40 years; the bands are high 10% to <20%, moderate 5% to <10% and low <5%, and ESC 2023 says these suggested thresholds are not definitive but are designed to prompt joint decision-making conversations.^[1]

Follow-up: What is severe target-organ damage?^[1]

• ESC 2023: eGFR <45 mL/min/1.73 m² irrespective of albuminuria; eGFR 45–59 with microalbuminuria (UACR 30–300 mg/g); proteinuria (UACR >300 mg/g); or microvascular disease in at least three different sites.^[1]

Branch C — Which drug, for whom?

Examiner: Walk me through the SGLT2 inhibitor and GLP-1 RA rows by population.^[1][4]

Strong answer:

• ASCVD: SGLT2 inhibitors and GLP-1 RAs with proven CV benefit are recommended to reduce CV events, independent of baseline or target HbA1c and of concomitant glucose-lowering medication (ESC 2023, each Class I, Level A).^[1]
• No ASCVD or severe TOD, SCORE2-Diabetes ≥10%: either may be considered to reduce CV risk (ESC 2023, Class IIb, Level C).^[1]
• Multiple ASCVD risk factors or established ASCVD: SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin or sotagliflozin) are also recommended to reduce the risk of HF hospitalisation (ESC 2023 Recommendation Table 22, Class I, Level A).^[1]
• T2DM at risk of HF (multiple ASCVD risk factors or established ASCVD): an SGLT2 inhibitor is recommended to reduce the risk of HF and CV death (ESC 2026 HF, Class I, Level A); a GLP-1 RA should be considered in T2DM with at least one other additional CV risk factor to reduce the risk of HF or CV death (ESC 2026 HF, Class IIa, Level A).^[4]
• Symptomatic HF: dapagliflozin or empagliflozin is recommended independent of LVEF to reduce the risk of HF hospitalisation or CV death (ESC 2026 HF, Class I, Level A); semaglutide or tirzepatide should be considered with symptomatic HF, LVEF ≥45% and BMI ≥30 kg/m², regardless of diabetes status, to reduce body weight and improve exercise capacity and QoL (ESC 2026 HF, Class IIa, Level B1).^[4]
• CKD: an SGLT2 inhibitor (canagliflozin, empagliflozin or dapagliflozin) is recommended in T2DM and CKD with an eGFR ≥20 mL/min/1.73 m² to reduce the risk of CVD and kidney failure (ESC 2023, Class I, Level A), and a GLP-1 RA is recommended at eGFR >15 mL/min/1.73 m² to achieve adequate glycaemic control, due to low risk of hypoglycaemia and beneficial effects on weight, CV risk and albuminuria (ESC 2023, Class I, Level A).^[1]
• CKD as defined by the entry criteria of DAPA-CKD, EMPA-KIDNEY and CREDENCE: an SGLT2 inhibitor is recommended in T2DM to reduce the risk of HF or CV death (ESC 2026 HF, Class I, Level A).^[4]

Follow-up: How do the US guidelines differ?^[2][3]

• ADA 2026 (10.40b and 10.40c, grade A): an SGLT2 inhibitor or a GLP-1 RA with demonstrated cardiovascular benefit is recommended in type 2 diabetes with established ASCVD, multiple ASCVD risk factors or CKD to reduce the risk of cardiovascular events.^[2]
• AHA/ACC/ADA/ASN CKM 2026: in adults with CKM stage 2 to 3 with T2D and increased risk for CVD (10-year PREVENT-CVD ≥7.5%), the treatment plan should include an SGLT2i or GLP-1-based therapy with demonstrated benefit to reduce cardiovascular events and mortality (COR 1, LOE A).^[3]
• CKM 2026, established disease: for adults with CKM stage 4 with T2D and ASCVD, either an SGLT2i or a GLP-1-based therapy with proven cardiovascular benefit is recommended to reduce the risk of cardiovascular events and cardiovascular mortality (COR 1, LOE A); with T2D and HF, SGLT2i should be prioritized as the first-line cardioprotective glucose-lowering medications to reduce cardiovascular death and HF hospitalizations (COR 1, LOE A).^[3]
• 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]
• Combination: ADA 2026 (10.40d, grade B) says that in type 2 diabetes with established ASCVD or multiple ASCVD risk factors, combined therapy with an SGLT2 inhibitor and a GLP-1 RA, each with demonstrated cardiovascular benefit, may be considered for additive reduction of the risk of adverse cardiovascular and kidney events; CKM 2026 says that in adults with CKM stage 4 with T2D and ASCVD, a combination of an SGLT2i and a GLP-1-based therapy can be beneficial to improve cardiovascular outcomes (COR 2a, LOE C-LD).^[2][3]
• CKM 2026 also says that in adults with CKM stage 2 to 3 with T2D and increased risk for CVD or multiple CKM risk factors, or both, combination therapy with a GLP-1-based therapy with proven benefit and an SGLT2i may be considered for reducing the risk of cardiovascular events beyond that conferred by a single agent (COR 2b, LOE B-NR).^[3]

Branch D — Drugs that worsen heart failure

Examiner: Which glucose-lowering drugs do you avoid in heart failure, and why?^[1]

Strong answer:

• Pioglitazone is not recommended for glucose-lowering in patients at risk of HF (or with previous HF) (ESC 2023, Class III, Level A); ESC 2023 reports an estimated 0.4% annualised absolute increase in HF with pioglitazone, and says HF with thiazolidinediones appears to be attributable to expanded plasma volume, with no evidence of myocardial toxicity.^[1]
• Saxagliptin is not recommended for glucose-lowering in patients at risk of HF (or with previous HF) (ESC 2023, Class III, Level B); in SAVOR-TIMI 53 (16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events, saxagliptin vs placebo, median 2.1 years) more patients were hospitalised for HF with saxagliptin (3.5% vs. 2.8%; HR 1.27).^[1][21]
• If additional glucose control is needed, ESC 2023 lists agents with a neutral effect on the risk of HF hospitalisation that should be considered for glucose-lowering treatment in T2DM at risk of or with HF: the listed GLP-1 RAs (lixisenatide, liraglutide, semaglutide, exenatide ER, dulaglutide, efpeglenatide) and sitagliptin or linagliptin (each Class IIa, Level A), and basal insulins glargine and degludec (Class IIa, Level B).^[1]
• Metformin: ESC 2023 says it should be considered for glucose-lowering treatment in T2DM and HF, in chronic and stable HF (Class IIa, Level B); 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.^[1][2]

Follow-up: Can a patient with ASCVD but no HF take pioglitazone?^[1]

• ESC 2023: if additional glucose control is needed, pioglitazone may be considered in T2DM and ASCVD without HF (Class IIb, Level B).^[1]

Branch E — The trials

Examiner: Name two SGLT2 inhibitor trials and what they showed.^[11][13]

Strong answer:

• EMPA-REG OUTCOME (7020 patients with type 2 diabetes at high cardiovascular risk treated, empagliflozin 10 mg or 25 mg vs placebo, median 3.1 years): primary composite outcome 10.5% in the pooled empagliflozin group vs. 12.1% with placebo (HR 0.86).^[11]
• DECLARE-TIMI 58 (17,160 patients with type 2 diabetes who had or were at risk for ASCVD, dapagliflozin vs placebo, median 4.2 years): MACE not lower (HR 0.93), but CV death or HF hospitalisation lower (HR 0.83).^[13]

Follow-up: What is new since the 2023 ESC guideline?^[19][20][1]

• SOUL (2025; double-blind, placebo-controlled superiority trial; 9650 participants aged 50 or older with type 2 diabetes, HbA1c 6.5 to 10.0%, and ASCVD, CKD or both; median follow-up 49.5 months): oral semaglutide lowered MACE against placebo (HR 0.86); ESC 2023 had listed oral semaglutide under proven CV safety.^[19][1]
• SURPASS-CVOT (2025; active-comparator-controlled, double-blind noninferiority trial; type 2 diabetes with ASCVD; 6586 tirzepatide and 6579 dulaglutide patients in the modified intention-to-treat population): tirzepatide was noninferior to dulaglutide for CV death, MI or stroke (HR 0.92; P = 0.09 for superiority).^[20]