Sulfonylureas and Body Weight Gain: Can This Side Effect Give us Insight into the Nature of Obesity?

Sulfonylureas are anti-diabetic drugs that often associate with a side effect of unwanted weight gain. Why might this weight gain occur? And what might it tell us about the etiology of overweight and obesity?

The Caloric Balance Hypothesis says that sulfonylureas can only make us fatter by first increasing our appetites and/or decreasing our ability to burn off calories.

The Lipophilia Hypothesis says medications can make us fatter simply by changing the hormonal balance of our fat tissue -- specifically by influencing energy balance at the level of the fat tissue itself. In other words, if a medication indirectly deranges the adipose tissue, then it could cause weight gain: any changes in appetite and energy expenditure would be downstream effects of this fundamental cause.

Which perspective is right? Let's investigate. A brief search of the online published papers about sulfonylureas delivers surprisingly intriguing returns.

1. For instance, this article: "Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea treated patients with type 2 diabetes."[1]

Don't get caught up in the stuff about how exenatide works. Instead, focus on this remark: "sulfonylureas, commonly prescribed antidiabetic drugs, are generally safe and efficacious... however... weight gain often accompanies their use."

2. Here's another interesting paper: "Effect of thiazolidinediones on body weight in patients with diabetes mellitus."[2]

The authors point out that: "treatment of diabetes mellitus with medications, including insulin, sulfonylureas, and TZDs, often leads to weight gain through a variety of mechanisms."

"A variety of mechanisms?" According to the Caloric Balance Hypothesis, you can only gain weight from one of two things: overeating or under exercising. Any mechanism that is not involved in manipulating "Calories In" or "Calories Out" does not square with the Caloric Balance Hypothesis. This is one of the reasons why it is so easy for an amateur non-scientist to pick holes in Caloric Balance. Practically everywhere you look you can find problems with the mainstream theory.

If the mainstream theory were airtight -- like the Law of Gravity appears to be, for instance -- it would be nearly impossible for someone to push it around so easily. Can you imagine an amateur physicist challenging the Law of Gravity as easily as we've challenged Caloric Balance?

Return to the home page

Return to main page on the discussion about what causes unexplained weight changes due to sulfonylureas and other factors


1. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD; Exenatide-113 Clinical Study Group. "Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea treated patients with type 2 diabetes." Diabetes Care. 2004 Nov;27(11):2628-35.

2. Fonseca V. "Effect of thiazolidinediones on body weight in patients with diabetes mellitus." Am J Med. 2003 Dec 8;115 Suppl 8A:42S-48S.

Sign up for my FREE report and email series. Finally, get CLARITY on all your calorie-related questions :)