Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).

Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.

The potential risks and benefits, the profile of adverse events, and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00279045 [ClinicalTrials.gov].).

Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.).

Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes.

JUDITH WYLIE-ROSETT, EDD, RD FOR THE DIABETES PREVENTION PROGRAM RESEARCH GROUPOBJECTIVE -Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants.RESEARCH DESIGN AND METHODS -For this study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up.RESULTS -A total of 1,079 participants were aged 25-84 years (mean 50.6 years, BMI 33.9 kg/m 2 ). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.51]; P Ͻ 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence.CONCLUSIONS -Interventions to reduce diabetes risk should primarily target weight reduction. Diabetes Care 29:2102-2107, 2006T he Diabetes Prevention Program (DPP) reported a 58% reduction in the incidence of diabetes over almost 3 years in subjects treated with an intensive lifestyle intervention (ILS) compared with participants treated with placebo (1). The ILS involved changes in diet and physical activity aimed at producing weight loss, but the study did not randomly assign each component of the intervention. However, there was variation in the change in diet, physical activity, and weight loss among ILS participants (2). Thus, we analyzed the relative contributions of changes in diet, physical activity, or weight loss to the reduction in diabetes incidence and assessed the contribution of diet and activity changes on weight loss. This report extends the understanding of how the ILS resulted in lower diabetes incidence (1) by assessing the impact of meeting intervention goals and on the changes in risk factors among individuals randomized to the ILS.RESEARCH DESIGN AND METHODS -The design, methods, recruitment, and characteristics of the DPP participants have been reported elsewhere (3,4). In summary, participants were aged Ն25 years, had a BMI of Ն24 kg/m 2 (Ն22 kg/m 2 in Asian Americans), and had impaired glucose tolerance during an oral glucose tolerance test, based on DPP criteria (5). Participants were excluded if they had diabetes or a number of other conditions or medications. All participants gave written informed consent after approval by the appropriate institutional review board. ILSThe ILS has been described (6). Goals were to reduce weight by 7% from baseline, to achieve and/or maintain at least 150 min per week of moderate physical activity, and to reduce total dietary fat to Ͻ25% of calorie...

A four-dose course of rituximab partially preserved beta-cell function over a period of 1 year in patients with type 1 diabetes. The finding that B lymphocytes contribute to the pathogenesis of type 1 diabetes may open a new pathway for exploration in the treatment of patients with this condition. (ClinicalTrials.gov number, NCT00279305.)

AimsWe previously reported that in the EMPA-REG OUTCOME® trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure.Methods and resultsPatients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1%) had heart failure at baseline. Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin [265/4687 patients (5.7%)] than with placebo [198/2333 patients (8.5%)] [hazard ratio, HR: 0.66 (95% confidence interval: 0.55–0.79); P < 0.001], corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years. Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics, including patients with vs. without heart failure, and across categories of medications to treat diabetes and/or heart failure. Empagliflozin improved other heart failure outcomes, including hospitalization for or death from heart failure [2.8 vs. 4.5%; HR: 0.61 (0.47–0.79); P < 0.001] and was associated with a reduction in all-cause hospitalization [36.8 vs. 39.6%; HR: 0.89 (0.82–0.96); P = 0.003]. Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups, but were no more common with empagliflozin than with placebo.ConclusionIn patients with type 2 diabetes and high cardiovascular risk, empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure.