JDBT Journal

Communication 

It has been almost 20 years since metformin was recognized as the first antidiabetic agent with a beneficial effect on cardiovascular events according to UKPDS’s results [1]. The disappointment at the failure of rosiglitazone, the first member of thiazolidinedione’s class, left sulfonylureas and their analogues, meglitinides, to be the most reliable alternatives to metformin, together with insulin. 

However, a series of trials on novel antihyperglycemic agents has recently showed that some of them have beneficial effects against cardiovascular events. In particular, two GLP-1 receptor agonists, injectable liraglutide [2] and oral semaglutide [3], together with two SGLT-2 inhibitors, empagliflozin [4] and canagliflozin [5] both taken orally, have achieved a reduction in complex cardiovascular endpoints in longitudinal, double-blinded RCT’s versus placebo. Subsequently, another trial followed which demonstrated that the benefit of empagliflozin is actually a class effect of SGLT-2 inhibitors [6]. Most recently, a new study tried to shed light on a possible mechanism [7]. 

American Diabetes Association (ADA) has already encompassed new evidence in its updated annual guidelines for the treatment of Diabetes Mellitus [8]. It is, therefore, expected that the upcoming review of ADA/EASD consensus, awaited to be released soon, will focus on recommendations on the treatment of certain groups of patients with high risk for cardiovascular events. Beyond glucose and HbA1c measurements, a target of diabetes treatment is to minimize the cardiovascular consequences and now it seems that we have effective tools to achieve it. 

Therefore, treatment decisions should be guided not only by glycemic targets but also by the burden of cardiovascular risk. As soon as there are available new drugs with evidenced beneficial cardiovascular effects, physicians have to offer their patients the chance to benefit and this is expected to be the concept of the new guidelines. 

1.                   Erratum in Lancet (1998) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352: 854-865.

2.                   Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, et al. (2016) Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. Engl J Med 375: 311-322.

3.                   Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, et al. (2016) Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 375: 1834-1844.

4.                   Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, et al. (2015) Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 373: 2117-2128.

5.                   Neal B, Perkovic V, Mahaffey KW, Zeeuw D, Fulcher G, et al. (2017) Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 377: 644-657.

6.                   Kosiborod M, Cavender MA, Fu AZ, Wilding JP, Khunti K, et al. (2017) Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation 136: 249-259

7.                   Packer M, Anker SD, Butler J, Filippatos G, Zannad F (2017) Effects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients with Heart Failure: Proposal of a Novel Mechanism of Action. JAMA Cardiol 2: 1025-1029.

8.                   Standards of Medical Care in Diabetes-2018. Diabetes Care 41: S1-S2.