Metformin in New European Guidelines for Treating Patients with Diabetes and Cardiovascular Disease

Introduction

Therapeutic options for type 2 diabetes have expanded remarkably in recent years. Moreover, ongoing studies continue to provide new insights into novel classes of antidiabetic drugs as well as specific preparations. Based on new evidence, ESC created an algorithm for antihyperglycemic treatment in diabetics, derived from the presence of CV disease/risk specific to the patient. Recommendations differ for patients with untreated diabetes and those with metformin initiated as first-line therapy.

Recommendations for Diabetics without CV Disease and High CV Risk

Patients who neither have CV disease nor high/very high CV risk should receive metformin as first-line therapy. Additional preparations are added to metformin if the target HbA_1c level is not achieved.

In choosing additional drugs, the updated treatment algorithm for type 2 diabetes, jointly issued by EASD and the American Diabetes Association (ADA) in December 2019, can be referenced: If minimizing the risk of hypoglycemia is crucial, DPP-4 inhibitors, SGLT2 inhibitors (SGLT2i), GLP-1 receptor agonists (GLP-1RA), or thiazolidinediones are appropriate. If weight reduction is the priority, GLP-1RA or SGLT2i are preferred.

Recommendations for Diabetics with CV Disease or High/Very High CV Risk

For patients with CV disease or high/very high CV risk who have not yet received antidiabetic treatment, SGLT2i or GLP-1RA is recommended as first-line therapy. If target HbA_1c levels are not achieved, metformin is added. If neither achieves HbA_1c compensation, a third antidiabetic drug is introduced.

It is important to note that the updated December 2019 EASD and ADA algorithm for antidiabetic treatment recommends starting treatment with both metformin and SGLT2i/GLP-1RA irrespective of glycosylated hemoglobin levels for these patients. This recommendation is based on the cardiovascular benefits observed with SGLT2i and GLP-1RA when combined with metformin, as demonstrated by the UKPDS study.

For individuals with diabetes and CV disease or high/very high CV risk already receiving metformin, SGLT2i or GLP-1RA is added to metformin. Metformin is not discontinued. If dual therapy does not ensure HbA_1c compensation, another antidiabetic drug is added.

In all cases, contraindications and the patient's tolerance to individual drugs must be considered.

Summary and Conclusion

To optimally choose antidiabetic drugs, physicians should be familiar with the pharmacological characteristics of different drug classes, their impact on the cardiovascular system and renal function, potential side effects, and take comorbidities into account.

The change in metformin’s position in current guidelines pertains to patients with untreated diabetes and CV disease or high/very high CV risk. ESC and EASD recommend metformin as a second-line drug after SGLT2 inhibitors or GLP-1 receptor agonists for these patients. (However, if patients are already on metformin, it should not be discontinued. First-line metformin therapy continues and SGLT2i or GLP-1RA is added.) Updated ADA and EASD recommendations from December 2019 place metformin first-line for all patients, with concurrent initiation of metformin and SGLT2i/GLP-1RA for those with newly diagnosed diabetes and existing CV disease or high/very high CV risk.

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Sources:

1. Cosentino F., Grant P. J., Aboyan V. et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Eur Heart J 2020; 41 (2): 255–323, doi: 10.1093/eurheartj/ehz486.
2. Buse J. B., Wexler D. J., Tsapas A. et al. 2019 Update to: 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 2020 Feb; 43 (2): 487–493, doi: 10.2337/dci19-0066.
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