{"id":996,"date":"2016-03-10T15:46:59","date_gmt":"2016-03-10T15:46:59","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=996"},"modified":"2017-08-21T11:02:11","modified_gmt":"2017-08-21T11:02:11","slug":"primary-care-corner-with-geoffrey-modest-md-glp1-added-to-metformin-and-basal-insulin-in-diabetes","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/10\/primary-care-corner-with-geoffrey-modest-md-glp1-added-to-metformin-and-basal-insulin-in-diabetes\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: GLP1 Added to Metformin and Basal Insulin in Diabetes"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>JAMA recently had a study comparing the A1c effects of\u00a0uptitrating basal insulin vs using a combo of basal insulin and a GLP-1 agonist (glucagon-like peptide-1) &#8212; see\u00a0JAMA. 2016;315(9):898\u200b.<\/p>\n<p>Details:<\/p>\n<ul>\n<li>26-week randomized study at 75 centers in 10 countries\u00a0 from Sept 2013 to Nov 2014 of patients\u00a0with uncontrolled diabetes\u00a0treated with glargine (20-50 U) and metformin (&gt;=1500mg\/d) and had A1c of 7-10% and BMI&lt;40<\/li>\n<li>557 patients (mean age 58.8, 49.7% women, 95% white, 40% Latino, BMI 31.7, duration of diabetes 11.5 years, mean\u00a0basal insulin dose of 31 U, 75% with hypertension, 61% with dyslipidemia, 44% on statins, 27% b-blockers, 65% of RAS inhibitors), randomized to\u00a0stopping the glargine and substituting\u00a0degludec\/liraglutide\u00a0(titrating to\u00a0max dose of 50 U degludec\/1.8mg of liraglutide) vs glargine (no max dose) and titrated twice-weekly to glucose target of 72-90 mg\/dL. Drug-company sponsored. (Degludec is a newly FDA-approved basal insulin)<\/li>\n<li>After titration, the mean dose of\u00a0degludec\/liraglutide was 41U\u00a0degludec\/1.48 mg\u00a0liraglutide and for glargine\u00a0was 66U.<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>\u200bDegludec\/liraglutide:\u00a0baseline A1c of 8.4% decreased 1.81 percentage points; 71.6% achieved A1c &lt;7% and 55.4% achieved A1c\u00a0&lt;6.5%<\/li>\n<li>Glargine:\u00a0baseline A1c of 8.2% decreased 1.13\u00a0percentage points; 47.0% achieved A1c\u00a0&lt;7% and 30.8% achieved A1c\u00a0&lt;6.5%<\/li>\n<li>Estimated treatment difference of -0.59\u00a0percentage points (-0.74 to-0.45\u00a0percentage points), meeting criteria for non-inferiority (p&lt;0.001) and also for statistical superiority (p&lt;0.001)<\/li>\n<li>Degludec\/liraglutide also associated with weight loss of -1.4 kg, vs weight gain with glargine of 1.8kg:\u00a0estimated treatment difference of -3.20 kg (-3.77 to -2.64 kg, p&lt;0.001) and fewer hypoglycemic episodes\/patient-yr of exposure (2.23 vs 5.05, corresponding to 28.4% on\u00a0degludec\/liraglutide and 49.1% on glargine), with estimated\u00a0hypoglycemia\u00a0rate ratio of 0.43 (0.30-0.61, p&lt;0.001)<\/li>\n<li>Adverse events: overall\u00a0events similar at\u00a0343.3 per 100 patient-year of exposure with\u00a0degludec\/liraglutide and 286.4 with glargine; serious events were 3.9 for\u00a0degludec\/liraglutide vs 6.7 for glargine. But\u00a0degludec\/liraglutide had much more minor GI adverse effects (9.4% with nausea vs 1.1% with glargine)<\/li>\n<li>Overall score on SF-36 patient questionnaire, assessing patient&#8217;s sense of their physical and mental well-being, improved with\u00a0degludec\/liraglutide\u00a0\u200bfrom baseline 47.4 to 49.0, but got worse with glargine, from 47.7 to 47.2, which was statistically significant at p&lt;0.001. I&#8217;m not\u00a0sure these are really clinically significant, but at least\u200b the GI adverse effects did not translate into a worsening of the SF-36<\/li>\n<\/ul>\n<p>So, this trial used a fixed dose combination injection (degludec\/liraglutide). The price in the UK is about the same or slightly less than the meds if bought individually. From my searching around, the combo drug is being considered by the FDA this year. Who knows what our price will be??\u00a0This is a drug-company sponsored study, but there are several attractive features of this combo injection:<\/p>\n<ul>\n<li>It seems to work well, and my experience using the combo of a GLP-1 agonist with basal insulin (mostly glargine) has been really pretty dramatically\u00a0positive. I have been prescribing either weekly exenatide (advantage of being weekly injection, disadvantage of being big needle injecting viscous material in order\u00a0to slow absorption, and patients having bumps under their skin for a while) or daily liraglutide (may work slightly better, is daily, but very small needle).<\/li>\n<li>As mentioned in prior blogs, the GLP-1 agonists are the only of the new meds that I am using (other than occasional pioglitazone, esp in those who are needle-averse, and pioglitazone is not really a new med). But GLP-1 agonists seem to be pretty target-specific (vs DPP-4 antagonists, which are oral and block degradation of GLP-1, but are not targeted and degrade other proteins in the body) and\u00a0restore a normal physiologic insulin\u00a0response to meals (the incretin effect), which is decreased for some reason in diabetics but is restored with injectable GLP-1 analogs.<\/li>\n<li>It is noteworthy that the average person in the study above had diabetes for 11.5 years. GLP-1 agonists rely on the pancreas to secrete insulin, and a concern is that patients with long-standing diabetes could have burnt-out pancreases. I have also had several patients with close to 20 years of diabetes who have responded well (though I have checked C-peptide levels in\u00a0several of them with very long-standing diabetes prior to initiating GLP-1 agonists, just to make sure the pancreas is working).<\/li>\n<li>There are some pretty useful advantages for the combo treatment: the A1c decreased (though we do need studies seeing if this translates into important clinical outcomes) and there was a reasonably big difference in weight loss vs gain with glargine.<\/li>\n<li>And, if there really is no price difference, it would be a lot easier to have one injection\/day.<\/li>\n<\/ul>\n<p>For other blogs on diabetes\/meds, see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/diabetes\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/diabetes\/<\/a>\u200b<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: GLP1 Added to Metformin and Basal Insulin in Diabetes  [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/10\/primary-care-corner-with-geoffrey-modest-md-glp1-added-to-metformin-and-basal-insulin-in-diabetes\/\">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-996","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\/996","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=996"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/996\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=996"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=996"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=996"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}