Читать книгу Clinical Dilemmas in Diabetes - Группа авторов - Страница 26

The Diabetes Prevention Program (DPP) enrolled 3234 nondiabetic adult subjects at 27 centers in the U.S. [18]. Eligibility criteria included FPG of 95–125 mg/dL and a 2‐h PG during a 75‐g OGTT 140–199 mg/dL. Subjects were assigned to one of three groups: (1) intensive lifestyle modification (goal ≥ 7% weight loss of initial body weight and ≥ 150 minutes of moderate intensity physical activity/week); (2) metformin 850 mg twice daily plus standard lifestyle recommendations; or (3) placebo plus standard lifestyle recommendations. Standard lifestyle recommendations were provided in writing and through annual brief individual sessions [73]. In contrast, the intensive lifestyle modification provided comprehensive instruction in a structured 16‐lesson curriculum.

The original DPP results were published after an average follow‐up of 2.8 years. The estimated cumulative incidence of DM at three years was significantly different among all groups: 28.9% in the placebo group; 21.7% in the metformin group; and 14.4% in the intensive lifestyle group. Weight loss was the main predictor of reduced DM incidence, with a hazard ratio per five‐kilogram (kg) weight loss of 0.42 (95% CI 0.35–0.51). Further, for every one kg of weight loss, there was a 16% reduction in risk of progression to DM [74].

Following randomization, DPPOS followed subjects for 15 years and metformin continued to be provided to the group originally assigned to it [75]. Over 15 years of follow‐up, the cumulative incidence of DM was 62% in the placebo group, 56% in the metformin group, and 55% in the intensive lifestyle group. At the end of DPPOS, the aggregate prevalence of microvascular outcomes – which included nephropathy, retinopathy, and neuropathy – did not differ among the 3 treatment groups. However, for women, intensive lifestyle intervention significantly reduced aggregate microvascular disease at 15 years compared to metformin and compared to placebo. Additionally, for those subjects with a baseline BMI ≥ 35 kg/m², the RR for the development of aggregate microvascular disease was significantly lower in the intensive lifestyle intervention group compared to the placebo group. Among participants whose most recent HbA1c was ≥ 6.5%, the intensive lifestyle intervention group showed statistically significant reductions in the aggregate microvascular outcome, retinopathy, and neuropathy compared with placebo and metformin.

Other benefits of intensive lifestyle changes were seen in DPP subjects [76]. From baseline to year three after randomization, hypertension increased in the placebo and metformin groups but decreased in the intensive lifestyle group. From baseline to year three, dyslipidemia progressed in all three groups but the progression was less in the intensive lifestyle group compared to the metformin and placebo groups. After a mean follow‐up of 3.2 years in the DPP, there were significant improvements in quality of life measures for the intensive lifestyle group, but not for the other two groups [77]. From a payer perspective, 10 years after randomization in DPP, intensive lifestyle changes were cost‐effective, and metformin was marginally cost‐saving compared to placebo [78].