{"id":1024,"date":"2016-04-20T13:43:45","date_gmt":"2016-04-20T13:43:45","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1024"},"modified":"2017-08-21T10:57:23","modified_gmt":"2017-08-21T10:57:23","slug":"primary-care-corner-with-geoffrey-modest-md-diabetes-dpp-4-inhibitors-and-the-risk-of-heart-failure","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/04\/20\/primary-care-corner-with-geoffrey-modest-md-diabetes-dpp-4-inhibitors-and-the-risk-of-heart-failure\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Diabetes DPP-4 Inhibitors and the Risk of Heart Failure"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>The FDA recently\u00a0came out with a safety\u00a0alert about 2 DPP-4 inhibitors and\u00a0the increased\u00a0risk of heart failure (released 04\/05\/2016) (see\u00a0<a href=\"http:\/\/www.fda.gov\/Safety\/MedWatch\/SafetyInformation\/SafetyAlertsforHumanMedicalProducts\/ucm494252.htm?source=govdelivery&amp;utm_medium=email&amp;utm_source=govdelivery\">http:\/\/www.fda.gov\/Safety\/MedWatch\/SafetyInformation\/SafetyAlertsforHumanMedicalProducts\/ucm494252.htm?source=govdelivery&amp;utm_medium=email&amp;utm_source=govdelivery<\/a>\u200b ).<\/p>\n<p>Details:<\/p>\n<ul>\n<li>Saxagliptin and alogliptin were singled out because of 2 clinical trials in\u00a0diabetic\u00a0patients with heart disease. In each trial more patients taking these meds were hospitalized for heart failure vs those on placebo\n<ul>\n<li>In the saxagliptin trial: 3.5% were hospitalized for heart failure (vs 2.8% on placebo). Risk factors included prior heart failure or kidney disease<\/li>\n<li>In the alogliptin trial: 3.9% were hospitalized for heart failure (vs 3.3% on placebo)<\/li>\n<\/ul>\n<\/li>\n<li>Recommendation by the FDA:\n<ul>\n<li><strong>We should consider stopping these drugs if the patient develops heart failure<\/strong><\/li>\n<\/ul>\n<\/li>\n<li>I believe these trials (not cited specifically\u00a0by the FDA) were the ones in the blog\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2013\/09\/10\/primary-care-corner-with-geoffrey-modest-md-new-diabetes-drugs-dpp-4-is-lower-a1c-not-cardiac-events\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2013\/09\/10\/primary-care-corner-with-geoffrey-modest-md-new-diabetes-drugs-dpp-4-is-lower-a1c-not-cardiac-events\/<\/a>\u200b . The saxagliptin one was clearly the one in the blog, the alogliptin one probably was (reviewing the article, they did not have any breakdown for developing heart failure in the article or\u00a0the supplementary materials. my guess is that the FDA got their hands on more\u00a0specific\u00a0data&#8230;.)<\/li>\n<\/ul>\n<p>Ironically, this FDA safety alert was published 2 weeks after the New England Journal of Medicine published a multicenter observational study of these meds and heart failure (N Engl J Med 2016;374:1145), looking at health care data from Canada, UK, and the US, using\u00a0a nested case-control design (matching each heart failure case to 20 controls from the same cohort), finding:<\/p>\n<ul>\n<li>1,499,650 patients involved, 29,741 hospitalized for heart failure\n<ul>\n<li>For those without history of heart failure: HR 0.86 (0.62-1.19)<\/li>\n<li>For those with history of heart failure: HR 0.82 (0.67-1.00)<\/li>\n<li>\u200bNo difference between those on DPP-4 inhibitors or GLP-1 agonists<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>So, how does this affect us?<\/p>\n<ul>\n<li>As I have mentioned many times in the past, I do not see any big benefit from using these drugs: the A1C benefit is not very large (about 0.3% in several studies, including the above 2 studies as well as\u00a0the sitigliptin one in the additional blog\u00a0below), DPP-4 is a pretty ubiquitous enzyme which deactivates lots of different bioactive peptides (i.e., DPP-4 inhibitors are hardly magic bullets), and it is really not so surprising that there may be significant collateral damage.<\/li>\n<li>The pretty small absolute increases in hospitalizations for heart failure (0.6-0.7%) is likely the tip of the\u00a0iceberg. Diabetics get lots of heart disease (the vast majority of diabetics, in\u00a0the 70-80% range, die from heart disease), most heart failure (I think) is treated as an outpatient and therefore\u00a0not showing up in statistics for hospitalizations, and the mortality from heart failure may well be higher in patients not enrolled in a study, where study personnel tend to follow patients closely and patients have easy access to them (this may be especially true\u00a0in areas of the country where there is not ready access to any\u00a0high quality outpatient\u00a0care or\u00a0hospitals.)<\/li>\n<li>Since\u00a0so many diabetic patients develop heart failure just because of their diabetes and other risk factors,\u00a0I think it is important that the FDA brings this drug association\u00a0to our attention (i.e., one would not think necessarily that the drug caused\u00a0the\u00a0heart failure). Not exactly sure what to do with the recent NEJM article, though it was a retrospective matching of patients from many trials (albeit a pretty big one)<\/li>\n<li>So, the DPP-4 inhibitors\u00a0are not on my list of meds to use, even in patients without known underlying heart or kidney disease&#8230;.. [Though, I should add, that I do use GLP-1 agonists, which have a much more dramatic effect on A1C levels, are more physiologic than exogenous\u00a0insulin or sulfonylureas, and are very specifically targeted to meal-related endogenous insulin release (the &#8220;incretin&#8221; effect). So, though it might surprise you,\u00a0I am really not against all new drugs&#8230;]<\/li>\n<\/ul>\n<p><a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/06\/24\/primary-care-corner-with-geoffrey-modest-md-dpp-4-inhibitors-and-cardiovascular-outcomes\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/06\/24\/primary-care-corner-with-geoffrey-modest-md-dpp-4-inhibitors-and-cardiovascular-outcomes\/<\/a> , which looks at sitigliptin (not one of the ones singled out by the FDA), showing very small effects on A1C levels, showing no increase in cardiovascular outcomes, but does bring up the point that for the minimal-effect on A1c, DPP-4 inhibitors block a ubiquitous enzyme on the surface of most cells and deactivates a variety of bioactive peptides.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Diabetes DPP-4 Inhibitors and the Risk of Heart Failure  [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/04\/20\/primary-care-corner-with-geoffrey-modest-md-diabetes-dpp-4-inhibitors-and-the-risk-of-heart-failure\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1024","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1024","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1024"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1024\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1024"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1024"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1024"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}