American Diabetes Association 73rd Scientific Sessions
June 21-25, 2013, Chicago, IL
The 73rd Scientific Sessions of the American Diabetes Association (ADA) — the largest diabetes meeting in the world — brought together 18,000 participants from all 50 states and 117 countries. In this issue, Cardiology Review covers 6 of the studies presented at the meeting: ACCORD, Look AHEAD, DCCT, Triple Therapy for New-Onset Diabetes, DIABAMON, and MOVE!
MOVE It and Lose It
A lifestyle-based intervention program using 8 to 12 weekly group sessions at Veterans Affairs (VA) hospitals focusing on nutrition, diet, exercise, social support, and exercise significantly reduced body weight in a large number of patients enrolled in the program. The program, Managing Obesity and Overweight in Veterans Everywhere (MOVE!), was designed for VA hospitals. Data from MOVE found that individuals who were more actively engaged in the programs — those participating in at least 8 sessions — lost 2.5% of their body weight in a 3-year period.
Lead investigator Sandra Jackson, MPH, of Emory University in Atlanta said that MOVE! was developed to see what lifestyle-based interventions could accomplish in the real-world setting. MOVE! was offered to patients at 130 VA hospitals and clinics in the United States, and has enrolled approximately 400,000 people. Ms Jackson said the weight loss was modest but sustained and that MOVE! is a good example of what a healthcare system can do with a small budget. Of the 135,000 people with at least 3 years of follow-up, patients lost an average of 1.3% of body weight. Participants who benefited most from MOVE! were those who attended at least 8 sessions and took the greatest advantage of the program.
The MOVE! program varied from center to center and allowed patients to set achievable goals for themselves. The sessions are modeled on the Diabetes Prevention Program (DPP).
Lawrence Phillips, MD, of Emory University, director of clinical studies at the Atlanta VA Medical Center and senior investigator of MOVE!, said the DPP asked patients to perform 150 minutes of exercise per week — something some of the VA patients would be unable to perform.
Of the participants enrolled in MOVE!, 38% had type 2 diabetes at enrollment. These patients were significantly more likely to participate actively in the program than were those without diabetes. Patients with diabetes lost significantly more weight than those without diabetes at 3 years. The researchers also observed a relationship between weight change at 6 months and the risk of diabetes at 3 years: the more weight patients lost, the less likely they were to develop diabetes. Participants who lost any weight or maintained their weight had a 16% lower risk of diabetes at 3 years compared with those who gained weight.
Jackson SL, Olson DE, Rhee M, et al. Lifestyle change works in a large national healthcare system. Presented at the American Diabetes Association 2013 Scientific Sessions, June 23, 2013, Chicago, IL. Abstract 382-OR.
DCCT 18 Years Later: Intensive Control Still Shows CV Benefits
Findings presented after 18 years of participation in the Diabetes Control and Complications Trial (DCCT) show that dramatic reductions in complications in people with type 1 diabetes mellitus, achieved with intensive glycemic control, are still being seen. The overall prevalence of diabetes mellitus complications is 50% lower among people with type 1 diabetes in the DCCT who were randomized to intensive glucose control compared with those who received conventional treatment— despite the finding that glycated hemoglobin (A1C) levels are no longer different between the 2 groups.
The long-term follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC), began in 1994 when the DCCT ended. DCCT/EDIC biostatistician John M. Lachin, ScD, of George Washington University, Rockville, MD, said the message of the DCCT has remained the same. “The A1C matters today, tomorrow, and for many, many years to come.”
After the DCCT ended and patients returned to their communities, glycemic control in the 2 groups became approximately the same. Thus, EDIC is measuring the ongoing impact of glycemic control that took place in the initial 10 years of the study. Investigators have called this “metabolic memory.” End points of retinopathy, nephropathy, neuropathy, and cardiovascular disease continue to be reduced among those originally in the intensivetreatment group. Investigators are also looking at mortality in the EDIC and disclosed that there is no increased mortality among the intensive-treatment group.
The extended analysis through 2012 found a 33% decrease in any cardiovascular event and a 35% reduced risk for nonfatal heart attack, stroke, or death from cardiovascular causes. These are still statistically significant and clinically meaningful, said Dr. Lachin.
The investigators said the take-away lesson concerning the results of this study are to start intensive diabetes management as soon as safely possible.
This study was presented at the ADA 2013 Scientific Sessions on June 22, 2013. Both the DCCT and the EDIC are funded by the US National Institutes of Health. Dr Lachin is a board member of Boehringer Ingelheim, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, and Reata and is a consultant for Andromeda Biotech and Magellan Health Services.
“Triple Therapy” for New-Onset Type 2 Diabetes Mellitus
A new way to start therapy for newly diagnosed type 2 diabetes mellitus patients was described in an interim study presented by Muhammad A. Abdul-Ghani of the University of Texas Health Science Center at San Antonio. The simultaneous “triple therapy” using metformin, pioglitazone, and exenatide (Byetta) was shown to produce greater and more durable reductions in glycated hemoglobin (A1C), less hypoglycemia, and less weight gain compared with conventional, stepwise, add-on treatments. Patients were able to achieve a mean A1C of 6% over the duration of the trial.
The comparator stepwise add-on therapy used metformin, glyburide, and basal insulin glargine.
Dr. Abdul-Ghani said the researchers believe that their findings might be clinically meaningful and may, in a larger study (this study involved only 155 patients), show differences in the risk of microvascular complications.
Dr. Abdul-Ghani explained that with conventional therapy, in which medications are added 1 at a time and a second is only started when needed, the A1C starts to slip over time, but with the triple therapy patients had exactly the same A1C at 6 months and at 2 years. Patients who reached 3 years of therapy in the study have maintained the same A1C. The investigation is slated to extend beyond 3 years.
This study was supported by the ADA, Amylin Pharmaceuticals, and Takeda.
Abdul-Ghani MD, Puckett C, Adams J, et al. Initial triple combination therapy is superior to add-on conventional therapy in newly diagnosed T2DM. American Diabetes Association 2013 Scientific Sessions: June 22, 2103, Chicago, IL. Abstract 72-OR.
PostHoc Analysis of ACCORD: Insulin Not Responsible for Increased CV Mortality Risk
An analysis of the data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial shows the dose of insulin used was not responsible for the increased risk of cardiovascular mortality among patients in the intensive-glycemic-control arm of the trial. Researchers reported that when the data are adjusted for multiple patient and on-treatment parameters, the risk of cardiovascular mortality is not significantly elevated among patients who received higher doses of insulin.
Lead investigator Elias Siraj, MD, of Temple University School of Medicine in Philadelphia, presented his findings at the ADA Scientific Sessions. “Given the patient population in ACCORD, and based on how we performed the analysis, we did not confirm insulin as an independent risk factor for cardiovascular death,” he said. He said it is difficult to make firm clinical recommendations based on the data because the study isn’t conclusive.
Dr. Siraj noted that patients in the ACCORD trial treated with intensive glycemic control were getting higher doses of insulin than those in the standard- treatment arm. After adjustment for multiple baseline covariates, he said, the risk was attenuated and no longer statistically significant. Upon further adjustments to reflect other drug treatment, weight change, average A1C, and glycemic treatment arm, the association was even further weakened.
Siraj ES, Rubin DJ, Miller ME, et al. The relationship between insulin exposure and cardiovascular mortality in the ACCORD trial. Presented at the ADA 013 Scientific Sessions, June 25, 2013, Chicago, IL. Abstract 386-OR.
CVD Reduced With Metformin, Higher With Rosiglitazone
A meta-analysis on the effect of metformin versus rosiglitazone on cardiovascular disease (CVD) found that metformin is associated with reduced risk of cardiovascular events, but that rosiglitazone (Avandia) increases the risk of heart failure and myocardial infarction (MI) and cardiovascular events.
Peter Boyle, MD, of the International Prevention Institute in Lyon, France, and lead researcher of the Diabetes Adverse Event Monitor (DIABAMON) project, said that although there have been significant reductions in the risk of cardiovascular mortality since the 1950s, the reduction in risk of coronary disease among patients with diabetes has not been as impressive. The DIABAMON project set out to investigate the risk of diabetes treatments.
The meta-analysis of 29 studies found that metformin was associated with a 10% reduction in the risk of cardiovascular events, with the medication associated with a 10% reduction in the risk of heart failure in 7 studies, and a 12% reduction in the risk of MI in 9 studies. Rosiglitazone, however, was associated with a 21% increased risk of cardiovascular events in 25 studies, a 27% increased risk of heart failure in 13 studies, and a 17% increased risk of MI in 21 studies.
The results reported for pioglitazone were less clear, according to Dr. Boyle. The meta-analysis found a 9% reduction in the risk of cardiovascular events and a 10% reduction in the risk of MI, but no association was found for heart failure.
Boyle P, Boniol M, Koechlin A, et al. Safety of glucose-lowering medications: the Diabetes Adverse Event Monitor (DIABAMON) project: II cardiovascular disease. Presented at the ADA 2013 Scientific Sessions, June 23, 2013, Chicago, IL. Abstract 1405-P.
Look AHEAD Fails To Show CVD Benefit for Lifestyle Intervention
The National Institutes of Health-sponsored Action for Health Diabetes (Look AHEAD) study looked at an intensive lifestyleintervention program that sought to achieve and maintain weight loss and fitness in type 2 diabetes mellitus (T2DM) patients. The intervention program was compared with a control group. The study was halted after a median follow-up of 9.6 years, because it failed to show that weight loss reduced the risk of cardiovascular events in overweight or obese adults with T2DM. The final results of Look AHEAD were presented at the ADA 2013 Scientific Sessions and are also published in The New England Journal of Medicine.
While the weight loss seen in the study was among the best ever reported in the literature, the study showed that an intensive lifestyle intervention (1200-1800 calories/d and 175 minutes of moderate-intensity physical activity per week) did not reduce the risk of cardiovascular events in people with type 2 diabetes.
Data from the trial did show that the intensive lifestyle intervention was associated with a 31% reduction in the risk of advanced kidney disease, and there was a significant 14% reduction in the risk of diabetic retinopathy with intensive lifestyle intervention, but no difference in the rate of diabetic neuropathy between the groups.
Fitness levels were also improved, as were other markers of metabolic risk, but low-density lipoprotein (LDL) cholesterol levels were not improved by the lifestyle interventions.
Responding to questions about why the study did not show a difference in CVD outcomes, investigators pointed out that the differential weight loss between intervention and control arms averaged 4% over the course of the study but only 2.5% at the end — a small difference that might not have been enough to have an effect on CVD events. They also noted that the intensification of medical management of CVD risk factors in routine medical care received by both groups may have may made relative benefit in the study group more difficult to show. The use of antihypertensive medications, statins, and insulin were, they noted, significantly lower in the intervention arm than in the control arm.
The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013. doi:10.1056/NEJMoa1212914. Available at www.nejm.org.