Safety and Side Effects of Once-Weekly GLP-1 Injections for Type 2 Diabetes | Research

The takeaway

Once-weekly GLP-1 receptor agonists (dulaglutide, exenatide ER, semaglutide) are generally well-tolerated, with GI side effects being most common and usually transient.

3 agents
Once-weekly GLP-1 RAs compared for safety: dulaglutide, exenatide ER, and semaglutide

What the researchers found

Once-weekly GLP-1 RAs have manageable safety profiles dominated by gastrointestinal side effects, with differences between agents that inform treatment selection.

Why it matters

With GLP-1 RAs increasingly prescribed for diabetes and obesity, clinicians need clear safety comparisons to choose the right agent for each patient.

The numbers in context

30 trials; 3 QW GLP-1 RAs; GI AEs most common; semaglutide DRC 3.0% vs 1.8% placebo (SUSTAIN 6); low hypoglycemia/pancreatitis/neoplasm rates

How the study worked

Narrative review comparing phase 3 clinical trial safety data for dulaglutide, exenatide ER, and semaglutide.

Who was studied

Type 2 diabetes patients across 30 Phase 3 clinical trials

What this study cannot tell us

Based on clinical trial data which may not capture all real-world safety signals. Head-to-head comparisons between agents are limited.

How to read the evidence

Review of phase 3 clinical trial data. Reliable safety information from well-designed trials.

When this study was published

Published in 2020. Additional safety data have accumulated with widespread clinical use.

The bigger picture

As GLP-1 RAs become a cornerstone of diabetes treatment, understanding their distinct safety profiles helps optimize prescribing and improve patient outcomes.

Questions still open

Which once-weekly GLP-1 RA has the best tolerability profile?
How do real-world side effect rates compare to clinical trial data?
Are there long-term safety concerns not captured in clinical trials?

Common questions

What are the most common side effects of weekly GLP-1 shots?

Nausea, vomiting, and diarrhea are the most common side effects, especially when starting treatment. These are usually mild and improve over time as the body adjusts to the medication.

Which weekly GLP-1 shot has the fewest side effects?

Each agent has a slightly different profile. The review compares them to help clinicians choose the best option for individual patients based on their specific health conditions and tolerance.

Read the original research

Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes.

Journal of clinical pharmacy and therapeutics, 45 Suppl 1(Suppl 1), 43-60

View on PubMed ↗Publisher’s paper ↗

Citation

Trujillo, Jennifer. (2020). Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes.. Journal of clinical pharmacy and therapeutics, 45 Suppl 1(Suppl 1), 43-60. https://doi.org/10.1111/jcpt.13225