Lipohypertrophy

Inject into the same patch of skin often enough and the fat underneath responds by thickening. The area may feel rubbery or slightly raised, and it often becomes less sensitive — which is precisely why people keep using it. The spot stops hurting, so it becomes the default, and the problem compounds.

The consequence is not cosmetic. Scarred, thickened tissue has a disorganized blood supply, so the drug deposited there is absorbed erratically. On a GLP-1 that means a week where appetite suppression feels weaker than usual, or a week where side effects arrive harder than expected, for no reason you can identify. Insulin users have known this pattern for decades; GLP-1 users are running into it now.

Every major label addresses it. Wegovy and Zepbound both instruct patients to rotate injection sites with each dose. The Saxenda label goes further and names a specific reason: rotate within the same region to reduce the risk of cutaneous amyloidosis, a related deposit that can build at overused sites. The labels also confirm that rotating costs you nothing in drug exposure — semaglutide and tirzepatide reached similar blood levels whether injected in the abdomen, the thigh or the upper arm.

The practical fix is a system, not a resolution. Divide each approved region into a small grid and move one position every week, cycling through abdomen, thigh and upper arm over a couple of months so no single square gets used more than a few times a year. Our rotation calendar generates that pattern, and the rotation cheat sheet is printable.

Worth asking your clinician: to actually feel your injection sites at a visit — lipohypertrophy is found by palpation, not by looking — and how long to rest an affected area before using it again. If your response to the drug has become unpredictable, this is a cheap thing to rule out before assuming the dose has stopped working. Our subcutaneous injection entry covers the technique side.