The cardiovascular safety of diabetes drugs was not considered as relevant until recent years. Traditionally, the control of diabetes was mostly founded on variations of glycated haemoglobin and this parameter has been shown to be inadequate for the prevention of cardiovascular disease . Type 2 diabetes is a systemic disease with multiple different mechanisms participating in the progression of the disease characterized by a markedly increase incidence of microvascular and macrovascular complications . So multiple interventions are probably required in order to effectively diminish the cardiovascular risk of type 2 diabetic patients, and among these interventions, the control of the most common modifiable cardiovascular risk factors, inadequate dietary habits including salt intake, blood pressure (BP), body weight, lipid disorders and smoking are absolutely mandatory.
In a very recent review, Ferrannini and DeFronzo  describe the possibilities of the different classes of antidiabetic drugs to protect the cardiovascular system in type 2 diabetes. This review concludes that we need more data to really know the effect of old and new antidiabetic drugs on cardiovascular outcome in type 2 diabetic patients. In this sense, many ongoing and recently finished studies will probably come with a definite answer to this question.
In this issue of the Journal of Hypertension, Imprialos et al. have made a complete review of the available data of the new class of antidiabetic drugs the sodium–glucose cotransporters 2 (SGLT-2) on some of the cardiovascular risk factors quoted earlier, body weight and natriuresis. These agents increase glycosuria and lead to an improvement in glucose control while simultaneously reducing BP and body weight probably as a consequence of inhibition of sodium reabsorption in the proximal tubule facilitated by glycosuria. This leads to a modest decrease in office BP of around 4–8/1–4 mmHg that could be higher using ambulatory BP monitoring according to the data contained in the review to which this editorial commentary is devoted . This salutary effect can contribute to improve the control of BP in type 2 diabetic patients and even to lower the amount of drugs, particularly diuretics and as a consequence a drop in cardiovascular risk could be expected . Simultaneously, other potentially salutary effects are facilitated by SGLT-2 drugs, such as weight decrease of 2.5–3 kg over 6–12 months after initiation of therapy and decrements in serum uric acid [5,6].
SGLT-2 inhibitors are drugs that reduce glycated haemoglobin by a similar amount when compared with other antidiabetic drugs through a totally different mechanism that does not facilitate the progressive decay in β-cell function ordinary seen with many antidiabetic drugs . This could facilitate the clinical use of these drugs and the salutary cardiovascular effects, albeit, modest could also contribute to it. In fact, in the most recently published guidelines, those of the American Diabetes Association and the European Association for the Study of Diabetes  and American Association of Clinical Endocrinologists , SGLT-2 drugs are recommended as the second antidiabetic drug after metformin.
It is clear, as recognized by Imprialos et al. that the limitation of this class of drugs is the loss of effect in the presence of a decreased renal function. Therefore, these drugs can only be used with estimated glomerular filtration rate (eGFR) above 60 ml/min per 1.73 m2, with the exception of canagliflozin and empagliflozin that can be used with eGFR values between 45 and 59 ml/min per 1.73 m2.
In conclusion, we must welcome the arrival of SGLT-2 inhibitors for the management of type 2 diabetes, but we need to wait for the results of the large ongoing trials of cardiovascular outcomes to see whether this class of drugs really differs from other classes of antidiabetic drugs by its salutary effects on macrovascular disease in diabetes.
Conflicts of interest
There are no conflicts of interest.
1. Zannad F, Stough WG, Pocock SJ, Sleight P, Cushman WC, Cleland JGF, et al. Diabetes clinical trials: helped or hindered by the current shift in regulatory requirements? Eur Heart J
2. Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J
2015; [Epub ahead of print].
3. Imprialos KP, Sarafidis PA, Karagiannis AI. Sodium–glucose cotransporter-2 inhibitors and blood pressure decrease: a valuable effect of a novel antidiabetic class? J Hypertens
4. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 3. Effects in patients at different levels of cardiovascular risk – overview and meta-analyses of randomized trials. J Hypertens
5. Ptaszynska A, Hardy E, Johnsson E, Parikh S, List J. Effects of dapagliflozin on cardiovascular risk factors. Postgrad Med
6. Clar C, Gill JA, Court R, Waugh N. Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open
7. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care
8. Handelsman Y, Bloomgarden ZT, Grunberger G, Umpires G, Zimmerman RS, Bailey TS, et al. American Association of Clinical Endocrinologists and American College of Endocrinology: clinical practice guidelines for developing a diabetes mellitus comprehensive care plan – 2015. Endocr Pract