The #1 Principle: Start Low, Go Slow
Most side effects are dose-related and improve with time. Starting at the lowest dose and titrating slowly gives your body time to adapt. Rushing to higher doses is the most common cause of intolerable side effects.
Side Effect Timeline
Weeks 1-4
Side effects often peak during initial weeks and dose increases
Weeks 4-8
Body begins adapting; most people see improvement
Weeks 8+
Most tolerate well; persistent issues may need dose adjustment
Managing Specific Side Effects
Nausea
~40% experience
The most common side effect. Usually worst during first weeks and after dose increases. Improves for most people.
Eating Strategy
Smaller, more frequent meals. Stop eating before you feel full—the medication slows digestion.
Food Choices
Bland, low-fat foods. Avoid greasy, spicy, or heavy meals that worsen nausea.
Ginger
Ginger tea, ginger chews, or ginger supplements have evidence for nausea relief.
Timing
Some find taking injection at bedtime means sleeping through worst nausea.
When to Call Your Doctor
Vomiting that won't stop, inability to keep down fluids, signs of dehydration. These need medical attention.
Constipation
~25% experience
Slowed gut motility means things move slower. Very common and manageable with the right approach.
Fiber
Increase gradually—too fast can worsen bloating. Psyllium husk (Metamucil) is gentle.
Hydration
Reduced eating often means reduced fluid intake. Consciously drink more water.
Movement
Regular walking or exercise helps gut motility. Sedentary behavior worsens constipation.
Magnesium
Magnesium citrate is a gentle, effective option. Start with 200-400mg at bedtime.
Fatigue
~15% experience
Often related to reduced calorie intake rather than the medication itself. Your body is adjusting to less fuel.
Protein Priority
Eating less? Make sure what you eat is nutrient-dense. Prioritize protein at every meal.
Blood Sugar
If on diabetes meds, blood sugar may drop too low. Work with your doctor to adjust.
Electrolytes
Reduced eating can mean electrolyte imbalances. Consider a supplement or electrolyte drinks.
Sleep
Calorie restriction can disrupt sleep. Maintain good sleep hygiene.
Injection Site Reactions
~5-10% experience
Redness, itching, or small bumps at injection site. Usually mild and resolve on their own.
Rotate Sites
Abdomen, thigh, upper arm. Never inject in the same spot twice in a row.
Room Temperature
Let medication warm to room temperature before injecting. Cold medication stings more.
Technique
Don't inject too shallow or too deep. Pinch skin, inject at 90°, release slowly.
Ice
Applying ice before injection can reduce discomfort and bruising.
When to Talk to Your Doctor
- Side effects aren't improving after 4-6 weeks at a stable dose
- You're unable to eat or drink enough to stay nourished
- Severe abdominal pain (could indicate pancreatitis)
- Signs of dehydration (dark urine, dizziness, dry mouth)
- Mood changes or depression
- Vision changes (if diabetic)
Your doctor may recommend: staying at current dose longer, stepping back to a lower dose, switching to a different GLP-1, or adding supportive medications.
The Bottom Line
Most GLP-1 side effects are manageable and improve with time. The key strategies: start low and titrate slowly, eat smaller meals, stay hydrated, increase fiber, and give your body time to adapt. Most people who push through the first few weeks find side effects become tolerable or disappear. If they don't improve, work with your doctor on dose adjustment—there's usually a way to make it work.
Sources
- FDA prescribing information for semaglutide and tirzepatide.
- Clinical trial adverse event data from STEP and SURMOUNT programs.
- Clinical practice recommendations for GI side effect management.