Cardio-renal protection is one of the most important goals in the management of type 2 diabetes mellitus. Therefore, SGED/SSED recommendations for the treatment of type 2 diabetes mellitus include a more rapid escalation of therapy when glucose control is inadequate and the use of agents with proven cardioprotective properties [1].
The goal of diabetes therapy is to delay or, at best, prevent the occurrence of complications without compromising quality of life [2]. This requires sustained glycemic control and effective management of cardiovascular risks. To achieve this, individual wishes and objectives should be defined during the patient’s follow-up in order to promote therapy adherence and motivation for accompanying measures. The consideration of the patient’s wishes and an individual goal setting as well as treatment strategy are central factors [2]. The choice of appropriate drug therapy can be complicated by the heterogeneity of type 2 diabetes mellitus (T2DM) and comorbidities present. The recently adapted Swiss recommendations for the treatment of T2DM guide general practitioners through the prescribing process, taking into account the latest scientific evidence [1].
Adjusted cardiovascular risk categories.
In line with the 2019 update of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) guidelines, the Swiss Society of Endocrinology and Diabetology (SGED/SSED) recommendation for the management of type 2 diabetes mellitus (2020) also adjusted the cardiovascular risk categories, which take into account the duration of diabetes and comorbidities [1,3]. In addition to patients with existing cardiovascular disease, patients with three or more additional risk factors are now assigned to the highest risk category [1]. These criteria are often met in T2DM patients or in the presence of microvascular complications (nephropathy, retinopathy, or neuropathy).
Role of SGLT-2 inhibitors in the management of T2DM.
Cardiovascular outcome studies are available for the SGLT-2 inhibitors canagliflozin, dapagliflozin, and empagliflozin and the GLP-1 receptor agonists lixisenatide, exenatide, liraglutide, semaglutide, and dulaglutide, which show a significant reduction in cardiovascular events and mortality [4–12]. Therefore, in the Swiss recommendations, at an estimated glomerular filtration rate (eGFR) >30 ml/min, early combination therapy consisting of metformin and an SGLT-2 inhibitor or GLP-1 receptor agonist is recommended (Fig. 1). If the set HbA1c target values are not reached, the other drug class (SGLT-2 inhibitor or GLP-1 receptor agonist) can be added in the next step (Fig. 2) [1].
In the presence of heart failure, early combination of metformin with an SGLT-2 inhibitor is recommended, as no benefit has been shown for GLP-1 receptor agonists in the context of heart failure [1].
In addition to cardiovascular considerations, renal risk factors must also be taken into account when treating T2DM. In patients with chronic kidney disease, SGLT-2 inhibitors can be used at an eGFR ≥45 ml/min (except ertugliflozin only at eGFR >60 ml/min), according to the SmPC [1]. However, study data are available for canagliflozin and empagliflozin showing safety up to an eGFR >30 ml/min [1].* Although the glucose-lowering effect of canagliflozin and empagliflozin decreases with decreasing eGFR, the benefit of cardio-renal protection remains even at low eGFR [1, 5, 7].
Conclusion
The adapted SGED/SSED recommendations for the management of type 2 diabetes focus on cardio-renal protection and serve as a guide for general practitioners on the optimal management of type 2 diabetes patients. By redefining cardiovascular risk groups based on the latest scientific evidence and early use of metformin in combination with SGLT-2 inhibitors or GLP-1 receptor agonists, cardio-renal prevention can be markedly improved [1].
* SGLT-2 inhibitors are not currently approved for renal protection. You can find the current drug information on www.swissmedicinfo.ch
Figure 1: Updated Swiss recommendations. Adapted from [1].
Figure 2: Key recommendations for general practitioners. Adapted from [1].
Literature:
- Lehmann, R., et al: Recommendations of the Swiss Society of Endocrinology and Diabetology (SGED/SSED) for the treatment of type 2 diabetes mellitus (2020). Swiss Society of Endocrinology and Diabetology (SGED/SSED). https://www.sgedssed.ch/diabetologie/sged-empfehlungen-diabetologie Last access 24.04.2020, 2020.
- Davies MJ, et al: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 2018. 41(12): 2669-2701.
- Cosentino, F., et al, 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J, 2020. 41(2): p. 255-323.
- Neal B, et al: Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med, 2017. 377(7): 644-657.
- Perkovic V, et al: Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med, 2019. 380(24): 2295-2306.
- Wiviott SD, et al: Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med, 2019. 380(4): 347-357.
- Zinman B, et al: Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med, 2015. 373(22): 2117-2128.
- Pfeffer MA, et al: Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med, 2015. 373(23): 2247-2257.
- Holman RR, et al: Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med, 2017. 377(13): 1228-1239.
- Marso SP, et al: Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med, 2016. 375(4): 311-322.
- Marso SP, et al: Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med, 2016. 375(19): 1834-1844.
- Gerstein HC, et al: Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet, 2019. 394(10193): 121-130.
Responsible for content and financed by Mundipharma Medical Company, Basel Branch.
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