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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Type 1 diabetes mellitus &#40;DM1&#41; is a heterogeneous disease caused by a complete defect in insulin secretion due to the destruction of pancreatic beta cells&#46; Most cases of DM1 are due to autoimmune destruction of beta cells &#40;DM1a&#41;&#44; while a small percentage are caused by nonautoimmune destruction or failure of beta cells &#40;DM1b&#41;&#46; DM1 represents 5&#8211;10&#37; of all cases of diabetes worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> In contrast&#44; DM2 is characterized by a combination of insulin resistance and an inadequate compensatory response to the action of insulin&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> Although DM1 can present at any age&#44; it characteristically affects children and adolescents&#46; Recently&#44; however&#44; the prevalence of DM2 has increased in young people&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Studies with euglycemic clamps have discovered that patients with DM1 have higher insulin resistance than patients without diabetes&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">2</span></a> which could partly explain this population&#39;s excessive cardiovascular risk&#46; It is believed that insulin resistance can be caused by a negative regulation of insulin receptors&#44; by the presence of glucotoxicity&#44; by increased secretion and growth hormone action and by the presence of hyperandrogenism in women&#46; Patients with DM1 and greater insulin resistance have been confirmed to present greater coronary calcification&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">3</span></a> Recent studies have shown that patients with DM1 have a hazard ratio of 3&#46;26 for myocardial infarction&#44; 2&#46;68 for heart failure and 2&#46;61 for ischemic stroke compared with the reference population without diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> The factors related to a greater risk of cardiovascular disease and mortality are glycated hemoglobin levels&#44; duration of the diabetes mellitus&#44; systolic blood pressure and low-density lipoprotein cholesterol values&#46; These risk factors have been reproduced in several studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Metformin is an antihyperglycemic that improves insulin sensitivity and constitutes the first-line therapy for patients with DM2&#46; The United Kingdom Prospective Diabetes Study showed that metformin therapy reduced the risk of macrovascular disease in patients with obesity and DM2&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> Metformin has also been shown to improve insulin sensitivity in patients with DM1 and has been observed to improve vascular function in children with DM1 and could therefore be considered a cardioprotective drug for this patient group&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> However&#44; the results of the Reducing With Metformin Vascular Adverse Lesions in Type 1 Diabetes 2 &#40;REMOVAL 2&#44; the broadest clinical trial to evaluate the effects of metformin in patients with DM1&#41; were not conclusive&#44; obtaining only small effects on glycemic control&#44; a modest weight reduction and ambiguous results for carotid intima-media thickness&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Sodium-glucose cotransporter-2 inhibitors &#40;SGLT2i&#41; block glucose and sodium reabsorption in the proximal tubule&#44; producing glycosuria and natriuresis&#46; Dual sodium-glucose cotransporter-2 and 1 inhibitors &#40;SGLT2&#47;1i&#41;&#44; such as sotagliflozin&#44; have an additional SGLT inhibitor effect at the gastrointestinal level&#44; delaying glucose and galactose absorption in the gastrointestinal tract&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The use of SGLT2i is recommended for patients with DM2 and established cardiovascular disease or moderate chronic renal failure to prevent major cardiovascular events &#40;including cardiovascular mortality&#44; myocardial infarction&#44; stroke and hospitalizations for heart failure&#41; and renal function impairment&#46; The recommendations are based on cardiovascular safety studies conducted with empagliflozin &#40;EMPA-REG OUTCOME&#41;&#44; canagliflozin &#40;CANVAS&#41; and dapagliflozin &#40;DECLARE&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In the current issue of <span class="elsevierStyleSmallCaps">Revista Cl&#237;nica Espa&#241;ola</span>&#44; Zhang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a> conducted a meta-analysis of 20 studies with 5868 patients to assess the use of metformin and SGLT2i in treating DM1&#46; The study showed that SGLT2i are more potent than metformin in reducing glycated hemoglobin levels &#40;-0&#46;4&#37; vs&#46; -0&#46;08&#37;&#44; respectively&#41; and body weight &#40;-3&#46;56<span class="elsevierStyleHsp" style=""></span>kg vs&#46; -2&#46;02<span class="elsevierStyleHsp" style=""></span>kg&#44; respectively&#41;&#44; while the reduction in insulin requirements was equivalent for the two drugs &#40;-6&#46;94 units&#47;day vs&#46;-3&#46;88 units&#47;day&#44; respectively&#41;&#46; In terms of safety issues&#44; the hypoglycemia risk was similar for SGLT2i and metformin &#40;odds ratio &#91;OR&#93;&#44; 0&#46;89 vs&#46; 1&#46;25&#44; respectively&#41;&#44; while the risk of diabetic ketoacidosis was higher for SGLT2i than for metformin &#40;OR&#44; 9&#46;21 vs&#46; 1&#46;00&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Based on the results of the REMOVAL 2 study&#44; metformin is unlikely to make headway in the treatment of DM1&#59; however&#44; the use of SGLT inhibitors is progressively increasing beyond its indication for patients with DM1&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> Several SGLT2i and SGLT2&#47;1i are undergoing evaluation by the US Food and Drug Administration and the European Medicines Agency as a joint treatment with insulin for DM1&#46; The drugs in the most advanced evaluation phases are sotagliflozin &#40;SGLT2&#47;1i&#41; and dapagliflozin &#40;SGLT2i&#41;&#46; Ipragliflozin &#40;SGLT2i&#41; has recently been approved in Japan for treating DM1 in combination with insulin&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Combined therapy with insulin and SGLT inhibitors is a promising treatment option for DM1 because it can facilitate glycemic control without a greater risk of hypoglycemia&#44; decreasing glycemic variability&#44; reducing insulin doses&#44; preventing insulin treatment-associated weight gain and&#44; potentially&#44; preventing cardiorenal morbidity and mortality in this population&#46; However&#44; this therapy is associated with a greater risk of severe ketoacidosis&#46; The use of this combination should therefore be restricted to expert physicians and selected patients&#46; Consensus documents have been developed to alert the medical community and mitigate the risk of diabetic ketoacidosis associated with use of SGLT inhibitors in patients with DM1&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a> The document describes the criteria necessary for starting treatment with SGLT inhibitors in patients with DM1 and preventing ketoacidosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; When ketonemia or ketonuria values are high&#44; patients should be instructed to discontinue the SGLT inhibitor treatment until the values return to normal&#46; Treatment to correct the ketosis should start swiftly to prevent severe ketoacidosis and hospitalization&#46; The key to treating ketosis is to maintain good hydration&#44; consume carbohydrates and continue administering insulin&#46; SGLT inhibitors should be discontinued for intercurrent acute processes&#44; surgery and scheduled procedures&#44; until the patient can restart oral intake&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ena J&#44; G&#243;mez-Huelgas R&#46; Metformina e inhibidores del cotransportador sodio-glucosa en el tratamiento de la diabetes mellitus tipo 1&#58; man&#233;jese con cuidado&#46; Rev Clin Esp&#46; 2020&#46; https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;rce&#46;2019&#46;09&#46;001&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; DM&#44; diabetes mellitus&#59; SGLTi&#44; sodium-glucose cotransporter inhibitors&#46;</p>"
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                  \t\t\t\t">&#8226; No pregnancy and no desire to become pregnant&nbsp;\t\t\t\t\t\t\n
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January - February 2020 Metformin and sodium-glucose cotransporter inhibitors as therapy for type 1 diabetes...
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Vol. 220. Issue 1.
Pages 24-26 (January - February 2020)
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Vol. 220. Issue 1.
Pages 24-26 (January - February 2020)
Editorial
DOI: 10.1016/j.rceng.2019.09.011
Metformin and sodium-glucose cotransporter inhibitors as therapy for type 1 diabetes mellitus: Handle with care
Metformina e inhibidores del cotransportador sodio-glucosa en el tratamiento de la diabetes mellitus tipo 1: manéjese con cuidado
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J. Enaa,
Corresponding author
ena_jav@gva.es

Autor para correspondencia.
, R. Gómez-Huelgasb
a Servicio de Medicina Interna, Hospital Marina Baixa, Villajoyosa, Alicante, España
b Departamento de Medicina, Hospital Regional Universitario de Málaga, Málaga, España
Related content
Efficacy and safety of metformin and sodium-glucose co-transporter-2 inhibitors in adults with type 1 diabetes: A systematic review and network meta-analysis
Rev Clin Esp. 2020;220:8-2110.1016/j.rceng.2019.06.011
Q Zhang, Y. Wu, Y Lu, X Fei
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Table 1. Criteria for Patients with Type 1 Diabetes Mellitus to Undergo Sodium-Glucose Cotransporter-2 Inhibitor Therapy.

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