sitagliptin -- ??more drug company shenanigans.

The preliminary results of the TECOS trial (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) was just released by the drug company (Merck), though formal release is expected in June at the Am Diabetes Assn meeting (and, i do not have an advanced copy to critique in detail).  This issue takes on added importance since there were 2 other large trials released recently on other DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors) finding possible increases in hospitalizations for heart failure. the SAVOR-TIMI 53 trial found a significant 27% increased hospitalization rate for heart failure in those randomized to saxagliptin (though no effect on cardiovascular outcomes overall, defined as cardiovascular death, nonfatal MI, or nonfatal ischemic stroke). the EXAMINE trial found a trend to higher heart failure hospitalization in those of alogliptin. based on these findings the FDA did recommend that these trials' results be added to the drugs' labels.  the TECOS trial, as reported by the drug company (see their press release: http://www.mercknewsroom.com/news-release/prescription-medicine-news/merck-announces-trial-evaluating-cardiovascular-outcomes-sit ), randomized 14,724 patients from 38 countries with a history of diabetes and cardiovascular disease to sitagliptin (Januvia) vs placebo and followed them 3 years, finding that it "achieved its primary endpoint of non-inferiority for the composite cardiovascular endpoint. among secondary endpoints, there was no increase in hospitalization for heart failure in the sitagliptin group versus placebo".

so, the issues here:
--the DPP-4 inhibitors add small amounts to diabetic control (varies somewhat depending on initial A1C, but in general about 0.5% decrease)
--the FDA several years ago allowed diabetic drugs to be marketed based only on A1C levels, a surrogote marker. there are no data on the clinical outcomes withSchedule
 DPP-4 inhibitors (and, i do find it a tad disconcerting that the Am Diab Assn, in their latest update, gives DPP-4 inhibitors an equal footing to all of the other alternatives as the second drug to use after metformin, though at least there are some data that others have some clinical benefit -- eg insulin, sulfonylureas, pioglitazone)
--Sitagliptin made $6 billion for Merck in 2014
--as succinctly put:  "Sanjay Kaul, a frequent FDA adviser, pointed out the paradox of the larfge commercial success of sitagliptin despite the absence of any proven clinical benefit: 'So, we have a drug that yields modest glycemic efficacy, is neutral with respect to cardiometabolic factors (lipids, weight, blood pressure), does not kill you or land you in a hospital, and yet is a blockbuster drug nearly five times over! What is the big news here? That it does not kill you or land you in a hospital? Or that it is a blockbuster drug nearly five times over without evidence of microvascular or macrovascular outcome benefit? Miracle of medicine or miracle of marketing?'   http://www.forbes.com/sites/larryhusten/2015/04/27/cardiovascular-outcomes-with-mercks-januvia-no-better-or-worse-than-conventional-care/, also quoted in Physician's First Watch)

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