One of the therapeutic paradoxes of our time is the coexistence of two families of drugs for diabetes, both of which lower blood glucose but one of which (the biguanide group) leads to weight loss in the obese, mildly diabetic patient while the other (the sulfonylurea group) is alleged to favor weight gain. Despite numerous investigations there is still doubt about the mechanisms by which these effects are accomplished.
Members of the sulfonylurea group stimulate the secretion of insulin, and, since insulin promotes fat synthesis, it is not strange that such treatment of the glycosuric diabetic helps to restore the weight he has lost while insulin deficient. What is strange is the concept, espoused by some, that administration of sulfonylurea drugs, or insulin itself, will increase body weight in the obese patient with mild diabetes, or even in the nondiabetic individual, both of whom have plenty of endogenous insulin already.
Weight Change With Orally Administered "Antidiabetic" Drugs. JAMA. 1970;213(10):1676–1677. doi:10.1001/jama.1970.03170360074016
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