Update on comorbidities in heart failure: type 2 diabetes
Heart failure in type 2 diabetics is associated with a significant increase in mortality. The most important comorbidities in heart failure were presented at the DGK 2023.
Hba1c level determines the occurrence of cardiovascular diseases
Elevated Hba1c levels in diabetes mellitus are associated with a whole range of risks for the cardiovascular system. Prof. Sedding presented important key figures to the audience. In the study presented, a 1% increase in Hba1c was associated with a 14% increase in the risk of fatal and non-fatal myocardial infarction. The same increase in Hba1c was associated with a 12% increase in the risk of fatal and non-fatal stroke. A 1% increase in Hba1c had the greatest effect on amputation/death from PAOD (peripheral artery occlusive disease). Here, the risk increased by 43%. With regard to heart failure (HF), a risk increase of 16% was recorded. It should be noted that the data presented by Prof. Sedding are from the year 2000.1,2
Cardiovascular risk in type 2 diabetics decrased over 20 years
A look at the epidemiological data of the last decades showed a positive development. The risk of heart attacks and strokes has steadily decreased in diabetic patients from 1990 to 2010. The risk of cardiovascular death in type 2 diabetes has also been reduced.1,3,4
Heart failure as a central cardiovascular problem in type 2 diabetics
Prof. Sedding pointed out that despite these initially positive figures, the incidence of cardiovascular disease in type 2 diabetics was about twice as high as in non-diabetics. In addition, the incidence and prevalence of heart failure in type 2 diabetics has increased, relatively speaking.1,5,6 The data presented by Anker et al. at the EASD 2020 showed that type 2 diabetics had an extremely significant increased risk of hospitalisation and death from heart failure compared to non-diabetics.1,7
Almost 90% increase in cardiovascular mortality in type 2 diabetics with heart failure
Prof. Sedding presented current epidemiological data on heart failure in type 2 diabetics from 2022 to the auditorium. According to these, type 2 diabetics were 2 to 5 times more likely to develop heart failure. In 30% of type 2 diabetics, heart failure was already present, whereby the number of unreported cases is currently still very high, according to Prof. Sedding. In 28% of type 2 diabetics, heart failure had not yet been diagnosed. In the majority of these undiagnosed cases, the ejection fraction would have been reduced (75% heart failure with reduced ejection fraction (HFrEF); 25% heart failure with preserved ejection fraction (HFpEF)). Another startling observation would be that the age spectrum of heart failure in type 2 diabetes had shifted significantly towards younger patients. Prof. Sedding emphasised in his presentation that the coexistence of type 2 diabetes and heart failure would be associated with a 50-90% increase in the risk of cardiovascular mortality.1,8
SGLT2 inhibitors as the only substance class with a positive effect on heart failure
Prof. Sedding presented the advantages and disadvantages of different antidiabetic drugs to his audience. Antidiabetic drugs differ significantly in their influence on the hospitalisation rate in heart failure. For example, a significantly increased risk for the hospitalisation rate in diabetics suffering from hypertensive heart failure (hHF) could be observed with the class of thiazolidinediones and saxagliptin.
In contrast, sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors) were associated with a significant reduction in the risk of hHF. In a large-scale meta-analysis, type 2 diabetics showed a significant decrease in hHF with SGLT-2 inhibitors compared to placebo or other antidiabetic drugs. Sedding emphasised that SGLT-2 inhibitors could significantly improve the prognosis of diabetic patients.1,9
SGLT2 inhibitors reduce the risk of cardiovascular death in type 2 diabetics and in non-diabetics with HFrEF
In both the DAPA-HF (evaluating dapagliflozin) and EMPEROR-Reduced (evaluating empagliflozin) trials, SGLT2 inhibitors were shown to reduce the combined risk of cardiovascular death or hospitalisation for heart failure for the following patient groups:
- Type 2 diabetics with heart failure with reduced ejection fraction (HFrEF)
- Non-diabetic with heart failure with reduced ejection fraction (HFrEF)
In a pre-specified meta-analysis of the two studies, effects on cardiovascular death or all-cause death were assessed, among others. Overall, there was a 13% reduction in total deaths. Cardiovascular deaths were reduced by 14% with SGLT2 inhibitor medication. The combined risk of cardiovascular death or first hospitalisation for heart failure was relatively reduced by 26%.1,10 Prof. Sedding highlighted in his presentation that SGLT2 inhibitors could now effectively treat heart failure (HFrEF; LV-EF ≤ 40%) for both type 2 diabetics and non-diabetics.1,11
SGLT2 inhibitors reduce the risk of cardiovascular death in heart failure regardless of ejection fraction
The two large-scale studies DELIVER and EMPEROR-Preserved investigated the therapeutic effects of SGLT2 inhibitors on cardiovascular mortality in HFpEF patients (HFpEF: heart failure with slightly reduced or preserved ejection fraction). In a pre-specified meta-analysis, the SOLOIST-WHF study was included in the analysis in addition to these two studies. This study included type 2 diabetics hospitalised for worsening heart failure. They received either the SGLT2 inhibitor sotagliflozin or a placebo. The primary endpoint was the total number of cardiovascular deaths, hospitalisations and emergency department visits due to heart failure.
In the meta-analysis, SGLT2 inhibitors reduced the risk of cardiovascular death and hospitalisation for heart failure in a wide range of heart failure patients. They thus had an important role as baseline therapy for heart failure, regardless of ejection fraction or care setting.1,12 This effect of SGLT2 inhibitors was observed for non-diabetics and type 2 diabetics.1
SGLT2 inhibitors: effective in non-diabetics and type 2 diabetics with HFrEF or HFpEF
SGLT2 inhibitors are thus suitable for heart failure therapy in non-diabetics and type 2 diabetics regardless of ejection fraction.1
Conclusions for medical practice
- Heart failure (HF) in type 2 diabetes mellitus (T2DM) is associated with a significant increase in mortality.
- The coexistence of type 2 diabetes with heart failure is associated with a 50-90% increase in risk of cardiovascular mortality.
- Type 2 diabetics are 2 to 5 times more likely to develop heart failure.
- Type 2 diabetics develop heart failure at a younger age.
- The number of unreported cases of heart failure in T2DM is high: in one third of type 2 diabetics, heart failure is initially undiagnosed.
- The class of thiazolidinediones and saxagliptin has a significantly increased risk of hospitalisation in type 2 diabetics suffering from heart failure (hHF).
- SGLT-2 inhibitors reduce the risk of hHF.
- SGLT2 inhibitors are effective heart failure therapy (HFrEF; LV-EF ≤ 40 %) for non-diabetics and type 2 diabetics.
- SGLT2 inhibitors reduce the risk of cardiovascular death in heart failure regardless of ejection fraction for HFrEF and HFpEF patients.
- Sedding, Daniel G., Prof. Dr. med., Session: Comorbidities in heart failure (mechanisms, therapeutic features) [Original German title: Komorbiditäten bei Herzinsuffizienz (Mechanismen, Therapeutische Besonderheiten)], Session Chair: Dr. Franz Goss; Prof. Dr. Stefan Frantz, 89. Annual Congress of the German Society for Cardiology (DGK), 08:35am, 14 April 2023.
- Stratton I.M. et al. (2000). Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12.
- Gregg EW. Et al. (2010). Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014 Apr 17;370(16):1514-23.
- Rawshani A. et al. (2017). Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes. N Engl J Med 2017; 376:1407-1418.
- Nichols G.A. et al. (2004). The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004 Aug;27(8):1879-84.
- Gustafsson I. et al. (2004). Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure. J Am Coll Cardiol. 2004 Mar 3;43(5):771-7.
- Anker et al. 56th annual meeting EASD 2020.
- Schütt K. et al. (2022). Position Papier Heart Failure and Diabetes Cardiology 2022 (Original title: Herzinsuffizienz und Diabetes Kardiologie 2022), 16:358–371.
- Singh A. K. et al. (2019). Heart failure hospitalization with SGLT-2 inhibitors: a systematic review and meta-analysis of randomized controlled and observational studies. Expert Rev Clin Pharmacol. 2019 Apr;12(4):299-308.
- Zannad F. et al. (2020). SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020 Sep 19;396(10254):819-829.
- Petrie M.C. et al. (2020). Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA. 2020 Apr 14;323(14):1353-1368.
- Vaduganathan M. et al. (2022). SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022 Sep 3;400(10354):757-767.