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• W2912573443 abstract "What is the logic, in the CANOE trial (July 10, p 103),1Zinman B Harris SB Neuman J et al.Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study.Lancet. 2010; 376: 103-111Summary Full Text Full Text PDF PubMed Scopus (180) Google Scholar of taking patients without diabetes and giving them diabetes medicines, which they might be interested in avoiding by avoiding diabetes? We think this regimen is motivated by an implicit preference for an alternative to community and clinical interventions to prevent disease through healthy lifestyles.2Pan XR Li GW Hu YH et al.Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the Da Qing IGT and diabetes study.Diabetes Care. 1997; 20: 537-544Crossref PubMed Scopus (3371) Google Scholar, 3Tuomilehto J Lindstrom J Eriksson JG et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med. 2001; 344: 1343-1350Crossref PubMed Scopus (8478) Google Scholar After giving up on lifestyle interventions, are pills an attractive alternative? CANOE, and DREAM before it, highlight a major problem of using diabetes medicines to prevent diabetes. The safety of rosiglitazone, used in both trials, is in question and the drug has now been removed from the European market. Whatever benefits might outweigh exposure to this medicine in patients with severe type 2 diabetes do not exist in the case of diabetes prevention. This point is particularly striking when one realises that diabetes is a surrogate outcome for a symptomatic condition (uncontrolled hyperglycaemia) or for elevated cardiovascular risk.4Montori VM Isley WL Guyatt GH Waking up from the DREAM of preventing diabetes with drugs.BMJ. 2007; 334: 882-884Crossref PubMed Scopus (35) Google Scholar Furthermore, because the market of healthy people at risk of diabetes is enormous, the number of individuals exposed to harm will be large, as would be the cost of the intervention itself and of caring for the harms it will cause. While high-income countries struggle to balance budgets after the economic depression and seek to restrict health-care spending, emerging economies—some of which have fared better (eg, Peru)—might be tempted to make the mistakes that high-income nations can no longer afford. The medicalisation of social problems and medication-mediated prevention of risk factors seems counterintuitive and wrong. We declare that we have no conflicts of interest. Rosiglitazone plus metformin to prevent type 2 diabetes mellitus – Author's replyThe main aim of the CANOE study was to determine whether low-dose combination therapy would be effective in preventing type 2 diabetes while minimising clinically relevant adverse effects. This strategy was chosen since half-maximum doses generally provide more than half-maximum effect and use of two agents with complementary mechanisms of action could be particularly desirable. Additionally, adverse effects are more commonly seen as one approaches maximum therapeutic doses. In this context, the CANOE trial showed that the combination of rosiglitazone and metformin was highly effective in preventing type 2 diabetes, with remarkably low rates of the common day-to-day adverse effects of these medications. Full-Text PDF" @default.
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• W2912573443 date "2010-10-01" @default.
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• W2912573443 title "Rosiglitazone plus metformin to prevent type 2 diabetes mellitus" @default.
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• W2912573443 doi "https://doi.org/10.1016/s0140-6736(10)61946-0" @default.
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