Treatment course and risks

Weeks 1 to 16: dose escalation

Wegovy starts at 0.25 mg weekly and rises every 4 weeks to 2.4 mg at week 17. Zepbound starts at 2.5 mg and rises by 2.5 mg after at least 4 weeks on each dose. The schedule is set to reduce gastrointestinal side effects, which occur mostly during escalation.[1][2][3]

Weeks 12 to 16: response check

Saxenda: stop if weight loss is under 4% at 16 weeks. Qsymia and Contrave: stop if weight loss is under 5% after 12 weeks on the full dose.[1][2][3]

Weeks 68 to 72: trial results

Mean weight loss was 14.9% on semaglutide 2.4 mg at 68 weeks and 20.9% on tirzepatide 15 mg at 72 weeks.[1][2]

Continuing treatment

In STEP 4, people who stayed on semaglutide lost another 7.9% over 48 weeks; those switched to placebo regained 6.9%. In SURMOUNT-4, staying on tirzepatide brought total loss to 25.3% at 88 weeks.[1][2]

After stopping

One year after stopping semaglutide, STEP 1 participants had regained two-thirds of the weight lost, and most cardiometabolic gains moved back toward baseline. In SURMOUNT-4, people switched to placebo regained 14.0%.[1][2]

Before surgery or sedation

Current Ozempic and Zepbound labels state that pulmonary aspiration during general anesthesia or deep sedation has been reported with GLP-1 drugs. Patients are told to inform providers of any planned surgery or procedure.[1][2]

Nausea, vomiting, diarrhea, constipation

In Wegovy trials: nausea 44% against 16% on placebo, diarrhea 30%, vomiting 24%, constipation 24%. Nausea led 1.8% to stop. In STEP 1 and SURMOUNT-1, most events were mild to moderate.[1][2][3]

Pancreatitis

Acute pancreatitis, including fatal hemorrhagic or necrotizing cases, has been seen with GLP-1 drugs. In Wegovy trials it was confirmed in 4 treated patients (0.2 per 100 patient-years) against 1 on placebo. The drug is stopped if pancreatitis is suspected.[1]

Gallbladder disease

Gallstones in 1.6% on Wegovy against 0.7% on placebo; cholecystitis 0.6% against 0.2%. A 76-trial meta-analysis found a relative risk of 2.29 for gallbladder or biliary disease in weight-loss trials.[1][2]

Thyroid C-cell tumor boxed warning

Semaglutide and tirzepatide cause thyroid C-cell tumors in rodents. Whether they do in humans is unknown. They are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2.[1][2][3]

Muscle and lean mass loss

In a 22-trial meta-analysis, lean mass made up about 25% of weight lost on GLP-1 drugs. Semaglutide 2.4 mg and tirzepatide 15 mg were among the least effective at preserving lean mass. The Zepbound label states fat mass loss exceeds lean mass loss.[1][2]

Compounded drug dosing errors

FDA has reports of overdoses, some requiring hospitalization, from compounded semaglutide in multi-dose vials, including confusion between milliliters, milligrams and units. A poison center series described 10-fold self-dosing errors.[1][2][3]

Mood, heart rate and blood pressure

Contrave carries a boxed warning for suicidal thoughts. Wegovy raised resting heart rate 1 to 4 beats per minute. The phentermine label lists rare primary pulmonary hypertension and valvular heart disease.[1][2][3]

Aspiration under anesthesia

GLP-1 drugs slow stomach emptying. Current labels state that pulmonary aspiration during general anesthesia or deep sedation has been reported in patients having elective procedures.[1][2][3]