Clinical Review

When Losing Weight Leads to Gaining Weight

Study data finds patients with diabetes taking canagliflozin experienced an increase of appetite and calorie intake without realizing it.


Just what someone with diabetes who’s successfully losing weight doesn’t want to hear: Losing weight may boost appetite significantly.

NIH researchers analyzed data from a year-long study of 242 people, of whom 153 were taking canagliflozin, a drug that increases the amount of glucose excreted in urine. That calorie loss led to a gradual weight loss that averaged 8 pounds. The patients were not “directly aware” of the calorie loss, the researchers say.

Related: A VA-Based, Multidisciplinary Weight Management Program

The participants could eat and drink without restriction. Using a math model, the researchers calculated the changes in the amount of calories consumed during the study. They found no long-term calorie intake changes in the 89 people on placebo. By contrast, for every pound of lost weight, the canagliflozin patients consumed about 50 calories more per day than they were eating before the study. After about 6 months, the extra appetite-fueled calories led to a plateau in weight loss.

The findings didn’t entirely surprise the researchers. In an earlier study of participants in a weight loss program not involving canagliflozin, something similar happened. Despite the dieters’ consistent efforts, increased appetite led to a calorie intake 3 times stronger than the changes in caloric expenditure that typically accompany weight loss, the researchers say—and a plateau.

Related: Keeping Diabetes at Bay

The study provides the “first quantification of the homeostatic control of energy intake in free-living humans,” the researchers say. While energy expenditure adaptations often are thought to be the main reasons for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult, the researchers say.

The conclusion? “Persistent effort is required to avoid weight gain,” the NIH report notes. Unfortunately, “weight regain is typical in the absence of heroic and vigilant efforts to maintain behavior changes in the face of an omnipresent obesogenic environment.”

Related: A Call to Action: Intensive Lifestyle Intervention Against Diabesity

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