Clinical perspective and future directions
“These results suggest that there are modest long-term cardiovascular disease benefits of therapies directed toward bringing glucose control to near-normal range in high-risk type 2 diabetes and that substantial and continuous glucose separation may be required to maintain these improvements,” Dr. Reaven concluded, adding that “recent studies demonstrating cardiovascular benefit with diabetes agents that only achieve modest improvements in glycemic control highlight the importance of also considering nonglycemic approaches to reducing cardiovascular disease events and mortality in these patients.”
Similarly, Dr. Emanuele concluded that there is a delayed beneficial effect of intensive glycemic control on kidney outcomes but that the effect dissipates as glycemic separation wanes.
However, in his commentary at the meeting, Dr. Gerstein stressed that the findings add value; in addition to showing, via mediation analyses, that HbA1c levels statistically explain the differences seen between the intensive and standard therapy arms at 10 years, the VADT and VADT-F findings also underscore the veracity of the ADA’s recommended target of HbA1c less than 7%, albeit “with all sorts of caveats.”
“But one point to make is that clinical trials do not tell you how to treat the patient in front of you. [They] just tell you what works on average for the average patient. ... You have to take the information you get from randomized trials and put it into your brain as a doctor and treat the patient,” he said.
He and several colleagues further explained this concept in a recent editorial (Diabetes Care. 2018 Jun;41[6]:1121-4) penned in response to new guidance statements published by the American College of Physicians advocating for relaxation of HbA1c control goals in patients with T2DM.
“The ACP proposal may encourage a step backward at a time when accumulating evidence from randomized, controlled trials calls for movement forward in the treatment of diabetes,” they wrote in the editorial entitled “A1c targets should be personalized to maximize benefits while limiting risks.”
Findings from those trials, including the VADT and VADT-F, continue to increase diabetes insights and inform care, and while there is not yet a statin-like “prescribe-and-go” treatment for diabetes, the findings represent a step in the right direction, Dr Gerstein said.
“All you have to do is look at all the clinical trials that are happening. We’re going to get there. ... This is not the end of the end, this is the beginning of the next phase,” he said.
The VADT and VADT-F were funded by the VA Cooperative Studies Program, the ADA, and the National Institutes of Health/National Eye Institute. Medication and additional support were provided by Aventis, GlaxoSmithKline, and Novo Nordisk Pharmaceuticals, which provided funding and supplies, and by Abbott Laboratory, Amylin, Eli Lily, Kos, Roche, and the University of Chicago, which also provided supplies. Dr. Reaven is an advisory panel member for Sanofi and has received research support from AstraZeneca and Novo Nordisk. Dr. Gerstein has received grants or other research support, honoraria, and/or consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Novo Nordisk, and Sanofi. Dr. Wiitala and Dr. Emanuele reported having no disclosures.