{"id":385970,"date":"2024-10-01T14:00:00","date_gmt":"2024-10-01T12:00:00","guid":{"rendered":"https:\/\/medizinonline.com\/?p=385970"},"modified":"2024-09-30T21:42:48","modified_gmt":"2024-09-30T19:42:48","slug":"sglt2-inhibitors-are-also-a-matter-of-the-heart","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/sglt2-inhibitors-are-also-a-matter-of-the-heart\/","title":{"rendered":"SGLT2 inhibitors are also a matter of the heart"},"content":{"rendered":"\n

There are up to six SGLT isoforms, whereby SGLT2 has come into particular focus in recent years due to its importance for type 2 diabetes mellitus.\nSGLT2 inhibitors lower blood glucose levels, but also enable blood pressure control in patients with hypertension and have a positive effect on the cardiovascular system. <\/strong><\/p>\n\n\n\n\n\n\n\n

SGLT2 inhibitors (SGLT2i) inhibit the function of SGLT2, thus preventing the absorption of glucose and enabling its excretion via the urine.\nAlthough SGLT2 inhibitors are not first-line drugs, they are used in combination with other drugs to control hyperglycemia in people with diabetes mellitus.\nThey also have the side effect of lowering blood pressure independently of blood glucose levels.\nPriscilla Ahwin and Diana Martinez from the Department of Biomedical Sciences, Cooper Medical School of Rowan University in Camden, USA, investigated the function of SGLT2 inhibitors in a review paper, including the importance of the SGLT2 receptor for blood glucose and blood pressure regulation [1]. <\/p>\n\n\n\n

SGLT2 is found in the early proximal tubule of the nephron.\nWhen the body begins to produce filtrate, which eventually becomes excretable urine, the role of SGLT2 in the nephron is to reabsorb glucose from the filtrate.\nMore than 90% of the glucose reabsorbed from the filtrate is accounted for by SGLT2, the remaining 10% by SGLT1.\nIn addition, SGLT2 also has an effect on blood pressure, as SGLT2i not only controls glycemic levels but also has a secondary effect on blood pressure.\nIn addition, SGLT2 is not only found in the kidney, but also in the central nervous system.\nSGLT2 receptors may exert cardioprotective effects via central nervous system mechanisms by influencing areas involved in cardiorespiratory regulation. <\/p>\n\n\n\n

SGLT2i lead to glucose excretion <\/h3>\n\n\n\n

One of the greatest risks for diabetes patients is hyperglycemia and its consequences.\nThe kidney is an important regulator of blood glucose homeostasis and this process is highly dependent on SGLT2.\nWhen waste products accumulate in the kidney, they are mixed with useful substances such as glucose.\nThe kidney has the task of filtering the glucose back into the body and excreting the waste products in the urine.\nSGLT2 works in a two-step process in which glucose and sodium enter the cell body through the SGLT2 transporter.\nThe accumulation of glucose in the cell leads to its exit into the plasma through the glucose transporter 2 (GLUT2), and the sodium-potassium ATPase maintains sodium concentration by pumping sodium into the plasma.\nIn an animal model with primates, tofogliflozin and phlorizin, competitive inhibitors of SGLT2, led to the excretion of glucose via the urine. <\/p>\n\n\n\n

SGLT2i are a new class of antidiabetic drugs that cause glucosuria by inhibiting glucose uptake in the proximal tubule of the nephron.\nFollowing the introduction of an SGLT2 inhibitor, SGLT1-mediated transport increases as a compensatory measure for glucosuria.\nHowever, inhibition of SGLT2 attenuates hyperglycemia and increases urine glucose.\nInstead, it travels through the nephron, is excreted in the urine and subsequently lowers blood glucose.\nStudies have shown that SGLT2i not only lowers blood glucose but also blood pressure in people with hypertension.\nThe mechanism by which blood pressure is lowered is not yet fully understood, but it is possible that osmotic and natriuretic diuresis reduces circulating plasma volume, which ultimately leads to a reduction in blood pressure, Ahwin and Martinez write.\nIn addition, SGLT2 can influence the sympathetic nervous system. <\/p>\n\n\n\n

A study by Seman et al. showed that the SGLT2i empagliflozin causes dose-dependent glycosuria in healthy male subjects without inducing hypoglycemia [2]. Similarly, a phase 1 study with the drug showed that an increase in dose led to greater cumulative glucose excretion. A single dose of empagliflozin can result in urinary glucose excretion of 46.3 to 89.8 g within 24 hours, compared to 5.84 g for placebo. Ultimately, treatment with empagliflozin stimulated urinary glucose excretion, resulting in an acute reduction in blood glucose levels and a chronic reduction in HbA1c<\/sub>.<\/p>\n\n\n\n

Empagliflozin caused clinically relevant reduction in blood pressure<\/h3>\n\n\n\n

In another study, empagliflozin proved to be effective in patients with coexisting diabetes and high blood pressure [3].\nPeople with hypertension and type 2 diabetes were recruited, with one group receiving either empagliflozin or placebo for 12 weeks.\nThe results showed that empagliflozin 10 mg lowered blood pressure by 3.44 mmHg, while empagliflozin 25 mg lowered blood pressure by 4.16 mmHg.\nIn line with this study, Ferdinand et al.\nconducted a study in which patients on empagliflozin vs. placebo showed a significant reduction in 24-hour ambulatory systolic blood pressure at week 24 [4].\nFurthermore, the effect was comparable to that of conventional antihypertensive monotherapies.\nHowever, the cardiorenal effects of SGLT2i appear to vary by ethnicity: A study by Kunutsor et al.\nfound that Asian and white patients with T2DM on SGLT2i had a lower risk of serious cardiovascular events and a lower risk of nephropathy [5].\nHowever, regional differences in SGLT2i efficacy were not observed. <\/p>\n\n\n\n

The advent of SGLT2 inhibitors shows that SGLT2 specifically regulates blood glucose levels by reabsorbing glucose through the early proximal tubule, the authors conclude.\nIn addition to lowering blood glucose levels, SGLT2i also lowered blood pressure in diabetics with hypertension and showed positive effects on cardiovascular risk. <\/p>\n\n\n\n

Literature:<\/p>\n\n\n\n

    \n
  1. Ahwin P, Martinez D.: The relationship between SGLT2 and systemic blood pressure regulation. Hypertens Res 2024; 47: 2094-2103; doi: 10.1038\/s41440-024-01723-6.<\/li>\n\n\n\n
  2. Seman L, et al: Empagliflozin (BI 10773), a Potent and Selective SGLT2 Inhibitor, Induces Dose-Dependent Glucosuria in Healthy Subjects. Clin Pharm Drug Dev 2013; 2: 152-161.<\/li>\n\n\n\n
  3. Tikkanen I, et al: Potential role of sodium glucose cotransporter 2 inhibitors in the treatment of hypertension. Curr Opin Nephrol Hypertens 2016; 25: 81-86.<\/li>\n\n\n\n
  4. Ferdinand KC, et al: Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients With Type 2 Diabetes Mellitus and Hypertension. Circulation 2019; 139: 2098-2109.<\/li>\n\n\n\n
  5. Kunutsor SK, et al: Racial, ethnic and regional differences in the effect of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes: a systematic review and meta-analysis of cardiovascular outcome trials. J R Soc Med 2023; doi: 10.1177\/01410768231198442.<\/li>\n<\/ol>\n\n\n\n

    <\/p>\n\n\n\n

    <\/p>\n\n\n\n

    InFo DIABETOLOGIE & ENDOKRINOLOGIE 2024; 1(3): 21<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    There are up to six SGLT isoforms, whereby SGLT2 has come into particular focus in recent years due to its importance for type 2 diabetes mellitus. SGLT2 inhibitors lower blood…<\/p>\n","protected":false},"author":7,"featured_media":385972,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"Type 2 diabetes, high blood pressure and cardiovascular risk","footnotes":""},"category":[11548,11359,11508,11384,11297,11460,11503],"tags":[78454,57198,44110,78455,78453,16272,12042],"powerkit_post_featured":[],"class_list":["post-385970","post","type-post","status-publish","format-standard","has-post-thumbnail","category-rx-en","category-cardiology","category-education","category-endocrinology-and-diabetology","category-general-internal-medicine","category-prevention-and-health-care","category-studies","tag-blood-pressure-control","tag-blood-sugar-level","tag-empagliflozin-en","tag-glucose-excretion","tag-sglt-isoforms","tag-sglt2-inhibitor-en","tag-type-2-diabetes","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-04-27 22:25:09","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":385964,"slug":"les-inhibiteurs-de-sglt2-sont-aussi-une-affaire-de-coeur","post_title":"Les inhibiteurs de SGLT2 sont aussi une affaire de c\u0153ur","href":"https:\/\/medizinonline.com\/fr\/les-inhibiteurs-de-sglt2-sont-aussi-une-affaire-de-coeur\/"},"it_IT":{"locale":"it_IT","id":385958,"slug":"gli-inibitori-sglt2-sono-anche-una-questione-di-cuore","post_title":"Gli inibitori SGLT2 sono anche una questione di cuore","href":"https:\/\/medizinonline.com\/it\/gli-inibitori-sglt2-sono-anche-una-questione-di-cuore\/"},"pt_PT":{"locale":"pt_PT","id":385953,"slug":"os-inibidores-sglt2-sao-tambem-uma-questao-de-coracao","post_title":"Os inibidores SGLT2 s\u00e3o tamb\u00e9m uma quest\u00e3o de cora\u00e7\u00e3o","href":"https:\/\/medizinonline.com\/pt-pt\/os-inibidores-sglt2-sao-tambem-uma-questao-de-coracao\/"},"es_ES":{"locale":"es_ES","id":385947,"slug":"los-inhibidores-de-sglt2-tambien-son-una-cuestion-de-corazon","post_title":"Los inhibidores de SGLT2 tambi\u00e9n son una cuesti\u00f3n de coraz\u00f3n","href":"https:\/\/medizinonline.com\/es\/los-inhibidores-de-sglt2-tambien-son-una-cuestion-de-corazon\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/385970","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=385970"}],"version-history":[{"count":3,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/385970\/revisions"}],"predecessor-version":[{"id":387348,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/385970\/revisions\/387348"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/385972"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=385970"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=385970"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=385970"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=385970"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}