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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article debates the value and cost of diabetes medications.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EIn answer to the question \u201cDiabetes Drugs: Are we getting value for money?\u201d Orville G. Kolterman, MD, Amylin Pharmaceuticals, San Diego, California, United States offered a resounding \u201cyes,\u201d while Edwin Gale, MD, University of Bristol, United Kingdom, countered with a firm \u201cno, not yet.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EDr. Kolterman began by pointing out that, as several important diabetes medications go off patent within the next 4\u20136 years, generic substitutions will add to the value received by patients. He further added that a consideration of drug costs must take into account the arduous FDA path that new drugs must traverse to pass through three clinical trial phases. The average process takes 8.5 years, and new estimates place the total cost of drug development and introduction to the market in excess of $1.5 billion (up from $802 million in 2000). Furthermore, the price of pharmaceuticals is determined by the marketplace and reflects not only the development expense, but a reward for the cumulative risks sustained by drug developers and manufacturers. Citing the pharma-biotech symbiosis, combining biotech\u0027s high-risk drug innovation with pharma\u0027s development and marketing prowess, he asked \u201cWhat would be the incentive to invest in a high-risk 14-year undertaking if the rewards were determined other than by the marketplace?\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThe value of \u201cme too\u201d drugs, an industry focus also often criticized, derives not only from prices restrained by increased competition, but also because agents do differ in terms of routes of metabolism and side-effects and tolerance profiles. Also, the lower risk for a company developing a \u201cme too\u201d drug helps fund riskier pioneering programs for that company as well. Finally, the value of improved lives enters the equation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EProf. Gale opened with a depiction of a pharmaceutical industry characterized by the face of a \u201cMr. Nice,\u201d who brings the new drugs that have the potential to truly change society and wants to make the world a better place, and the face of a \u201cMr. Nasty,\u201d who believes only in the bottom line, complains about any government restrictions, and sues anyone who enters the market with a cheaper product. In the final analysis, Mr. Nasty\u0027s truth is: \u201cDrug companies are machines for making money.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThat machine has been a successful one, consuming, for example, proportions of the US economy that have grown geometrically since 1990 (+573%) versus the arithmetic growth progression of the overall economy (+57%). During the last decade, drug costs have increased faster than other components of diabetes care. But at the same time that newer, more expensive drugs have been emerging, clinical evidence is not showing them to be more efficacious than traditional agents, or their benefits are marginal or relegated to second-line use.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003E\u201cThere is no evidence that increased drug costs have paid for themselves,\u201d Prof. Gale said. Furthermore, the focus on newer agents has diverted attention from lifestyle change, a known means to prevent or treat diabetes. \u201cThe attempt to substitute pharmacotherapy for lifestyle change is a recipe for failure,\u201d he stated.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EProf. Gale offered the ironic concept of the NNNT (the number needed \u003Cem\u003Enot\u003C\/em\u003E to treat), pointing out that the savings from treating 80 diabetes patients with metformin instead of rosiglitazone would fund one diabetes nurse educator. He concluded, \u201cFar from paying for themselves, more expensive therapies for diabetes have important negative costs.\u201d In addition, he pointed to excessive profit-taking in the industry, as witnessed by the fact that the profit margin of the top 10 American drug companies (18.5% of sales), far exceeded the Fortune 500 median of 3.3%.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EProf. Gale noted the emerging demand for evidence-based medicine and appropriate government regulation which should lead to drug costs that are linked to evidence-based value. He closed with a plea for collaboration between industry and the medical profession.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe second debate in this evidence-based medicine session centered around the question of whether GLP-1-based therapies will substitute for sulfonylureas. Jens Juul Holst, MD, University of Copenhagen, Denmark, took the affirmative position (although he noted that GLP-1 based therapies were still in their \u201cneonatal period\u201d), listing the therapeutic virtues of GLP-1 in type 2 diabetes. These include improvements in insulin secretion and biosynthesis, improved \u03b2-cell function, proliferation, and differentiation reductions in \u03b2-cell apoptosis favorable effects on gastric emptying, satiety, appetite, food intake, and weight plus beneficial cardiovascular effects.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003ETurning to GLP-1 receptor activators, he noted favorable incretin mimetic (eg, with exanatide) effects on HbA1c, body weight, cardiovascular risk factors, insulin dose, and health-related quality of life.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003ESimilarly, he reviewed liraglutide as added to glimepiride or metformin, and the DDP-IV inhibitors (vildagliptin, sitagliptin) alone and in combination with metformin, finding a wide range of benefits. Comparing the benefits of DPP-4 inhibitors\/GLP-1 receptor agonists benefits with those of sulfonylureas, Prof. Holst pointed to issues of weight gain, hypoglycemia, durability of effect, effects on \u03b2-cell health and cardiovascular risk factors all to favor the former. One study [Maedler K et al. \u003Cem\u003EJ Clin Metab Endocrinol\u003C\/em\u003E 2005] demonstrated sulfonylurea-induced \u03b2-cell apoptosis in cultured human islets. \u201cThese little facts,\u201d he concluded, \u201ctalk for themselves.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EDavid R Matthews, MD, The Oxford Centre for Diabetes, Endocrinology and Metabolsim, Oxford, United Kingdom, said \u201cno\u201d to substituting GLP-1 based therapies for sulfonylureas. He suggested that the idea of substitution is the wrong concept given that polypharmacy has proven to be necessary in contemporary treatment of hypertension, cancer, heart failure, pain relief and rheumatic illnesses. Pointing to studies of exenatide added to metformin, sulfonylureas or a combination of the two that demonstrated the benefit of polypharmacy on HbA1c levels and weight gain, Prof. Matthews suggested that the treatment benefits of the newer agents over sulfonylureas are marginal (less than 0.3% at 5 years for rosiglitazone, for example).\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EProf. Matthews urged caution with the DPP-IV inhibitors and GLP-1 analogs because of the paucity of long-term trials and of cardiovascular disease outcome trials, and noted potential pleiotrophic effects of DPP-IV inhibition as well. Even the long-term effects of GLP-1 agonist- and homolog-induced weight loss need to be evaluated. On the other hand, there is an evidence base for significant heart attack reductions with metformin and reduced diabetes-related endpoints and microvascular disease with sulfonylureas. He added that while \u03b2-cells do fail faster on sulfonylureas, the effect is comparatively small.\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EAt the same time, the cost differences are enormous, Prof. Matthews said, with exanatide about 15 times more expensive than gliclazide or glibenclamide. The developing world cannot afford these new injectable therapies, and in the developed world expensive therapies divert a large proportion of resources.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EMatthews concluded that sulfonylureas are low-cost and highly efficacious drugs for type 2 diabetes. \u201cTherefore,\u201d he said, \u201cwe should not abandon sulfonylureas that are tried and tested in favor of the new and sexy.\u201d\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/6\/21\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1948328451\u0022 data-figure-caption=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure1\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/6\/21\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/6\/21\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure1\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/7\/6\/21\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10833\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2007 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/7\/6\/21.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm85e\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm85e\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}