BACKGROUND:Obesity is a common health problem that requires a long-term care approach. We systematically reviewed long-term (≥2 y) studies investigating dietary/lifestyle, pharmacologic, and surgical weight loss methods to assess (1) weight loss efficacy, defined by absolute weight loss and the proportion of subjects with ≥5% weight loss, (2) effects of weight loss on cardiovascular risk factors, and (3) applicability of findings from studies to everyday clinical practice.METHODS:The MEDLINE, HealthSTAR, and the Cochrane Controlled Trials databases were searched for studies investigating the long-term efficacy of weight loss methods in overweight and obese adults. Data were extracted for (i) weight loss after 1 y (pharmacologic studies only), 2 y, 3 y, and 4 y, (ii) proportion of subjects with ≥5% weight loss at the end of follow-up, and (iii) changes (end-of follow-up minus baseline values) in blood lipids, fasting blood glucose, and systolic and diastolic blood pressure.RESULTS:Dietary/lifestyle therapy provides <5 kg weight loss after 2–4 y, pharmacologic therapy provides 5–10 kg weight loss after 1–2 y, and surgical therapy provides 25–75 kg weight loss after 2–4 y. Weight loss of ≥5% baseline weight is not consistently associated with improvements in cardiovascular risk factors and these benefits appear to be intervention specific and occur mainly in people with concomitant cardiovascular risk factors. Weight loss studies have methodologic limitations that restrict the applicability of findings to unselected obese people assessed in everyday clinical practice. These limitations include an inadequate study duration, large proportions of subjects lost to follow-up, a lack of an appropriate usual care group, and a lack of reporting of outcomes in high-risk subgroups.CONCLUSIONS:Dietary/lifestyle and pharmacologic weight loss interventions provide modest weight loss, and may improve markers of cardiovascular risk factors although these benefits occur mainly in patients with cardiovascular risks. Studies investigating weight loss have methodologic limitations that restrict the applicability of findings to obese patients assessed in clinical practice.