Methods of treatment in subjects suffering from diabetes mellitus or obesity are provided. The methods comprise ablation of a region of the small intestine in the subject, in particular ablation of a region of the duodenum. The ablation may be a mechanical, electrical, thermal, radiative, or chemical ablation and may in some cases target a sensory nerve. The methods may, in some cases, comprise the step of administering an active agent directly to the small intestine in the subject, in particular administering the active agent directly to the duodenum.