The Two Questions Patients Ask Most About GLP-1 Medications

Brenda Johnson, MATS, PA-C is a physician assistant at Lone Star Center for Health & Wellness in San Antonio. She specializes in medically supervised weight loss and hormone optimization. Below are the two questions patients ask her most often before and during GLP-1 therapy. For more information, contact us or request an appointment online. We are conveniently located at 8233 Fredericksburg Rd, San Antonio, TX 78229.

Question 1. What are the side effects of GLP-1 Medication?

Brenda: The most common side effects are gastrointestinal—nausea, diarrhea, constipation, vomiting, bloating, and reflux. They happen because these medicines slow stomach emptying and change appetite signals in the brain. That is how they help you feel full. It is also why the gut often protests during the first weeks and after each dose increase.

In the landmark STEP 1 trial of once-weekly semaglutide 2.4 mg, gastrointestinal events occurred in 74.2% of people on medication versus 47.9% on placebo. Nausea was reported by 44.2% versus 17.4%, diarrhea by 31.5% versus 15.9%, vomiting by 24.8% versus 6.6%, and constipation by 23.4% versus 9.5%. Most events were mild to moderate and improved with time. About 4.5% stopped the medicine because of gut symptoms, compared with 0.8% on placebo (Wilding et al., 2021).

A pooled analysis of STEP 1–3 found the same pattern: nausea 43.9%, diarrhea 29.7%, vomiting 24.5%, and constipation 24.2% with semaglutide 2.4 mg. Nearly all events were non-serious (99.5%) and mild to moderate (98.1%). They clustered during dose escalation. Permanent discontinuation for GI events was 4.3%. Importantly, weight loss was similar whether or not a person had GI symptoms—those symptoms are not what drives most of the weight loss (Wharton et al., 2022).

Tirzepatide shows a similar profile. In SURMOUNT-1, nausea occurred in 24.6% to 33.3% of people on tirzepatide versus 9.5% on placebo. Diarrhea ranged from 18.7% to 23.0% versus 7.3%. Events were mostly mild to moderate and occurred mainly during dose escalation. Treatment was stopped for any adverse event in 4.3% to 7.1% of tirzepatide groups versus 2.6% on placebo (Jastreboff et al., 2022).

What I tell patients in clinic

• Start low and go slow. Skipping titration almost always worsens nausea.
• Eat smaller, blander, lower-fat meals, especially the day of the injection and the next two days.
• Sip fluids all day. These medicines can blunt thirst as well as hunger. Dehydration makes nausea and constipation worse.
• Protect muscle: aim for adequate protein and resistance training. Rapid weight loss of any kind includes some lean mass.
• Call us for severe or persistent belly pain (especially if it radiates to the back), inability to keep fluids down, signs of dehydration, or yellowing of the skin or eyes. Gallbladder events and rare pancreatitis need prompt evaluation.

Question 2. What happens if I stop taking it?

Brenda: For most people, a large share of the lost weight returns after the medicine is stopped, and some of the cardiometabolic gains ease back toward baseline. That is not a personal failure. Obesity is a chronic condition. When the pharmacologic signal is removed, appetite and weight regulation typically rebound.

In the STEP 1 trial extension, adults who had lost a mean of 17.3% of body weight on semaglutide 2.4 mg plus lifestyle support regained a mean of 11.6 percentage points in the year after both the medicine and the structured lifestyle program were withdrawn. Net loss at week 120 was 5.6% from starting weight—about one-third of the original loss remaining. Most cardiometabolic improvements also moved back toward baseline (Wilding et al., 2022).

The same story appears with tirzepatide. In SURMOUNT-4, participants lost a mean of 20.9% during a 36-week open-label lead-in. Those who continued tirzepatide for another 52 weeks lost an additional 5.5% (25.3% total from the start). Those switched to placebo regained 14.0% from the week-36 weight and finished with 9.9% net loss from baseline. About 89.5% of people who stayed on tirzepatide kept at least 80% of their lead-in weight loss, versus 16.6% of those who stopped (Aronne et al., 2024).

A later analysis of people withdrawn from tirzepatide found that most regained 25% or more of the lost weight within a year, and greater regain tracked with greater reversal of waist circumference, blood pressure, lipids, and glycemic measures (Horn et al., 2025).

What this means for planning

• Think of GLP-1 therapy the way we think of blood pressure or cholesterol medicine: it treats a chronic condition while it is taken.
• If a pause or stop is planned, do it with a clinician. A slower taper is ideal and a written nutritional plan give you a better chance of holding more of the loss.
• Protein intake, resistance training, sleep, and follow-up visits matter more—not less—after the medicine is reduced or stopped.
• Some patients do well on a lower long-term maintenance dose. That decision is individual and should be based on response, tolerability, cost, and health goals.

Quick comparison from the trials

Topic	Semaglutide 2.4 mg	Tirzepatide 10–15 mg	Take-home

Most common side effects	Nausea ~44%; diarrhea ~32%; vomiting ~25%; constipation ~23% (STEP 1)	Nausea ~25–33%; diarrhea ~19–23%; constipation ~12–17% (SURMOUNT-1)	Gut symptoms are expected, usually early, and usually temporary.
Stopped for GI / any AE	4.5% stopped for GI events (STEP 1)	4.3–7.1% stopped for any AE (SURMOUNT-1)	Most people stay on therapy when titration and meal timing are coached.
After stopping	Regained ~2/3 of lost weight in 1 year off drug (STEP 1 extension)	Regained 14 percentage points after withdrawal; only 16.6% kept ≥80% of loss (SURMOUNT-4)	Ongoing treatment, or a planned maintenance strategy, is usually required.

Topic

Most common side effects

Semaglutide 2.4 mg

Nausea ~44%; diarrhea ~32%; vomiting ~25%; constipation ~23% (STEP 1)

Tirzepatide 10–15 mg

Nausea ~25–33%; diarrhea ~19–23%; constipation ~12–17% (SURMOUNT-1)

Take-home

Gut symptoms are expected, usually early, and usually temporary.

Topic

Stopped for GI / any AE

Semaglutide 2.4 mg

4.5% stopped for GI events (STEP 1)

Tirzepatide 10–15 mg

4.3–7.1% stopped for any AE (SURMOUNT-1)

Take-home

Most people stay on therapy when titration and meal timing are coached.

Topic

After stopping

Semaglutide 2.4 mg

Regained ~2/3 of lost weight in 1 year off drug (STEP 1 extension)

Tirzepatide 10–15 mg

Regained 14 percentage points after withdrawal; only 16.6% kept ≥80% of loss (SURMOUNT-4)

Take-home

Ongoing treatment, or a planned maintenance strategy, is usually required.

When to call the clinic

• Severe or persistent abdominal pain, especially with vomiting or pain that moves to the back
• Inability to keep down fluids for more than 24 hours, dizziness, or markedly reduced urine
• Yellowing of the skin or eyes, dark urine, or pale stools
• A sudden change in mood, vision, or allergic swelling after an injection
• Plans to stop, skip several weeks, become pregnant, or start a new medicine that affects blood sugar