{"id":7605,"date":"2011-04-06T18:30:44","date_gmt":"2011-04-06T22:30:44","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?p=7605"},"modified":"2011-07-19T17:44:28","modified_gmt":"2011-07-19T21:44:28","slug":"large-study-finds-wide-differences-in-risks-among-diabetes-drugs","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2011\/04\/06\/large-study-finds-wide-differences-in-risks-among-diabetes-drugs\/","title":{"rendered":"Large Study Finds Wide Differences in Risks Among Diabetes Drugs"},"content":{"rendered":"<p>A very large observational study has found an increase in death and  cardiovascular risk in people taking insulin secretagogues (ISs)  compared with those taking metformin. Tina Ken Schramm and colleagues, <a href=\"http:\/\/eurheartj.oxfordjournals.org\/content\/early\/2011\/04\/05\/eurheartj.ehr077.abstract\">reporting in the <em>European Heart Journal<\/em><\/a>,  analyzed data from the entire population of Denmark and identified  107,806\u00a0 people who initiated therapy with an IS or metformin. The  study, they say, is the first &#8220;to analyse major cardiovascular endpoints  with all currently approved ISs monotherapies in a nationwide setting.&#8221;<\/p>\n<p>The analysis found a consistent increase in deaths and cardiovascular  events associated with the most commonly used ISs, including  glimepiride, glibenclamide, glipizide, and tolbutamide, while the risks  associated with gliclazide and repaglinide were not significant.<\/p>\n<p>Here are the hazard ratios and confidence intervals for mortality  for the following drugs, compared with metformin, in patients <em>without<\/em> a history of MI:<\/p>\n<ul>\n<li> glimepiride: 1.32 (1.24\u20131.40)<\/li>\n<li> glibenclamide: 1.19 (1.11\u20131.28)<\/li>\n<li> glipizide: 1.27 (1.17\u20131.38)<\/li>\n<li> tolbutamide: 1.28 (1.17\u20131.39)<\/li>\n<\/ul>\n<p>Here are the risks for mortality for the following drugs in patients <em>with<\/em> previous MI:<\/p>\n<ul>\n<li>glimepiride: 1.30 (1.11\u20131.44)<\/li>\n<li>glibenclamide: 1.47 (1.22\u20131.76)<\/li>\n<li>glipizide: 1.53 (1.23\u20131.89)<\/li>\n<li> tolbutamide: 1.47 (1.17\u20131.84)<\/li>\n<\/ul>\n<p>In <a href=\"http:\/\/eurheartj.oxfordjournals.org\/content\/early\/2011\/04\/05\/eurheartj.ehr019.extract?sid=7aadafc8-6eac-476b-b193-9a619ed6b5db\">an accompanying editorial<\/a>, Odette Gore and Darren McGuire write  that the study is &#8220;among the most robust&#8221; due to its size, thereby  giving it enough power to evaluate the individual agents studied. They  warn against interpreting the study to mean that the drugs may cause  harm, especially since metformin has been associated with an  approximately 40% risk reduction for cardiovascular events and death  compared with placebo.<\/p>\n<p>Further, they write, an &#8220;important and novel finding of the present  study is the variability of  the estimates of hazard associated with  individual insulin  secretagogues, suggesting that some may be better  than others with  regard to the outcomes assessed.&#8221; In the absence of  trial data, drug choices &#8220;remain grounded primarily on clinical  judgement.&#8221;<\/p>\n<p>&#8220;Ideally,&#8221; they conclude, &#8220;all drugs used to treat   T2DM should undergo CV efficacy and safety evaluation, but for drugs   that are already approved, and especially for those that are generic, it   remains to be determined where the responsibility will fall to support   such large and expensive clinical trial evaluations.&#8221;<\/p>\n<p>&nbsp;<\/p>\n<p><strong> <\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A very large observational study has found an increase in death and cardiovascular risk in people taking insulin secretagogues (ISs) compared with those taking metformin. Tina Ken Schramm and colleagues, reporting in the European Heart Journal, analyzed data from the entire population of Denmark and identified 107,806\u00a0 people who initiated therapy with an IS or [&hellip;]<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,7],"tags":[200,788,787],"class_list":["post-7605","post","type-post","status-publish","format-standard","hentry","category-general","category-prevention","tag-diabetes","tag-insulin-secretagogues","tag-metformin"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/7605","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/196"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=7605"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/7605\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=7605"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=7605"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=7605"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}