John P. is a 48-year-old white male patient with type 2 diabetes 
mellitus who presents to his primary-care clinician for a routine physical. He is 5’11” and weighs 200 lb. He says that he wants to lose weight but has been unable to do so. He has been “on and off” diets for most of his adult life. His father had diabetes, and while John knows that losing weight will be good for his health, he says he does not like exercising, is very sedentary, and enjoys eating out with his wife. 

John was diagnosed with type 2 diabetes 4 years ago and was prescribed metformin 500 mg twice a day (BID). Three years ago, his metformin dose was increased to 1,000 mg BID, and 1 year ago, a sulfonylurea was added. In addition, the patient is taking an angiotensin-­converting enzyme (ACE) inhibitor for hypertension and a statin for hypercholesterolemia. Two years ago, he started a low-carbohydrate diet and lost 30 pounds, but he has regained most of the weight he lost. He is frustrated that his blood glucose is increasing.

Weight loss is notoriously difficult to achieve. This is partially attributed to an intrinsic physiologic bias that favors energy conservation as well as alterations in neural signaling caused by obesity that facilitate overeating and energy 
conservation.1-3The physiologic causes of obesity are exacerbated by an environment that encourages overconsumption of calorically dense food with limited opportunities for physical activity.

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Losing as little as 5% to 10% of initial body weight improves metabolic risk factors for cardiovascular disease, prevents or delays the development of type 2 diabetes, and improves other adverse consequences of obesity.4,5Although intensive lifestyle interventions have been associated with an average weight loss of 7% to 10% at 1 year in clinical trials, most individuals are unable to achieve clinically significant weight loss or maintain a weight-reduced state with lifestyle interventions alone.