Implications of Look AHEAD for clinical trials and clinical practice

Abstract

Look AHEAD was a randomized clinical trial designed to examine the long-term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow up of 9.6 years was not reduced in the intensive lifestyle group relative to the control group. This finding is discussed, with emphasis on its implications for design of clinical trials and clinical treatment of obese people with type 2 diabetes.

Family physician-led, team-based, lifestyle intervention in patients with metabolic syndrome: results of a multicentre feasibility project

“…34 Contrary to the Look AHEAD trial, our intervention focused on reversing MetS (and not only weight loss) and emphasized changes in the dietary composition (e.g., the Mediterranean diet pattern). 35 The relevance of purely reversing MetS has been criticized by some 6,7 and therefore it is noteworthy that our intervention was associated with a 17% relative risk reduction in the 10-year risk of acute myocardial infarction from baseline.…”

Low Carbohydrate Diets and Type 2 Diabetes: What is the Latest Evidence?

“…For people with type 2 diabetes, there is evidence from a large, long-term RCT suggesting that higher carbohydrate diets can improve weight loss, glycemic control, and CVD risk factors (although not CVD mortality) [ 40 ]. The Look AHEAD trial (ClinicalTrials.gov identifier, NCT0017953) reported greater weight loss, improvements in glycemia and CVD risk factors, and reduced risk of microvascular complications, depression, sleep apnea, and urinary incontinence at 9.6-year follow-up in those allocated an intensive lifestyle education (ILE) program compared to standard diabetes education (DES) [ 41 ]. Those in the ILE group were encouraged to increase physical activity and adopt an energy-reduced, low fat, partial meal replacement plan.…”

Clinical Update: Cardiovascular Disease in Diabetes Mellitus

“…265 The narrow 95% CI for the primary outcome was consistent with the conclusion that the absence of between-group differences was not due to lack of a sufficient number of primary endpoint events. 285 …”

“…291 Another parallel goal is to prevent weight gain, and certain glucose-lowering medications are more likely to result in weight gain (insulin, sulfonylureas and thiazolidinediones), while others are either weight neutral (dipeptidyl peptidase 4 [DPP4] inhibitors, or gliptins), and some result in weight loss (metformin, glucagon-like peptide [GLP]-1 receptor agonists and sodium-glucose cotransporter [SGLT]2 inhibitors, or gliflozins). 292 Interestingly, the use of insulin does not preclude weight loss, 285 and short- and long-term weight loss can occur with adherence to treatments. The most effective strategies for weight loss in diabetes include a Mediterranean diet 287 and an intensive program combining diet and physical activity.…”