From the Guidelines
Stomach pain and vomiting associated with GLP-1 receptor agonists can be managed by eating smaller meals, avoiding fatty or spicy foods, and staying well-hydrated, as these medications slow gastric emptying and can worsen discomfort if too much is eaten. To mitigate these symptoms, it is essential to start with a low dose and titrate upward slowly, as dose-dependent adverse effects are more frequent with short-acting than long-acting drugs 1. The most frequently reported side effects of GLP-1 receptor agonists are nausea and vomiting, which are usually transient for longer-acting GLP-1RAs and can be mitigated by gradual dose escalation and educating patients to reduce meal size 1.
Some key points to consider when managing stomach pain and vomiting with GLP-1 receptor agonists include:
- Eating smaller meals to reduce the burden on the stomach
- Avoiding fatty or spicy foods that can irritate the stomach
- Staying well-hydrated to prevent dehydration
- Contacting a healthcare provider if symptoms persist, as they may recommend temporarily reducing the dose or slowing down dose escalation
- Considering over-the-counter medications like antacids for temporary relief
- Being aware that most gastrointestinal side effects tend to improve within 4-8 weeks as the body adjusts to the medication
It is crucial to remember that these medications work by affecting gut hormones and slowing digestion, which contributes to weight loss but can also cause digestive symptoms. If severe or persistent symptoms occur, especially if accompanied by dehydration or inability to keep fluids down, seeking medical attention immediately is essential. According to the latest evidence, the management of stomach pain and vomiting associated with GLP-1 receptor agonists should prioritize a gradual dose escalation and patient education on reducing meal size 1.
From the FDA Drug Label
In a clinical pharmacology study in patients with renal impairment, including end-stage renal disease (ESRD), no clinically relevant change in dulaglutide pharmacokinetics (PK) was observed. In the 52-week trial in patients with type 2 diabetes and moderate to severe renal impairment, the PK behavior of TRULICITY 0.75 mg and 1.5 mg once weekly was similar to that demonstrated in previous clinical studies 8.8 Gastroparesis Dulaglutide slows gastric emptying. TRULICITY has not been studied in patients with preexisting gastroparesis. Use TRULICITY with caution in patients with gastroparesis. 10 OVERDOSAGE Overdoses have been reported in clinical studies. Effects associated with these overdoses were primarily mild or moderate gastrointestinal events (e.g., nausea, vomiting) and non-severe hypoglycemia.
Gastrointestinal side effects of GLP-1s, such as nausea and vomiting, are possible due to the delay in gastric emptying caused by these medications.
- Dulaglutide slows gastric emptying, and its use is cautioned in patients with gastroparesis.
- Overdoses of dulaglutide have been associated with mild or moderate gastrointestinal events, including nausea and vomiting. It is essential to use caution when prescribing GLP-1s, such as dulaglutide, to patients with a history of gastrointestinal issues, including gastroparesis 2.
From the Research
Gastrointestinal Side Effects of GLP-1 Receptor Agonists
- GLP-1 receptor agonists (GLP-1 RAs) are known to cause gastrointestinal side effects, including nausea, vomiting, and diarrhea 3
- The incidence of gastrointestinal adverse events (AEs) is higher with GLP-1 RAs compared to placebo or conventional treatment 3
- Different dose regimens of GLP-1 RAs have varying effects on the incidence of gastrointestinal AEs, with taspoglutide 30 mg once weekly and lixisenatide 30 μg twice daily having the highest incidence of nausea and vomiting, and lixisenatide 30 μg twice daily having the highest incidence of diarrhea 3
Mechanism of Action and Effects on Gastric Emptying
- GLP-1 RAs work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, and decelerating gastric emptying, which helps to reduce post-meal glycemic increments 4
- The effects of GLP-1 RAs on gastric emptying decrease over time due to tachyphylaxis 4
- Short-acting GLP-1 RAs, such as exenatide b.i.d. and lixisenatide, have reduced effectiveness on overnight and fasting plasma glucose, but maintain their effect on gastric emptying during long-term treatment 4
Comparison of GLP-1 Receptor Agonists
- Different GLP-1 RAs have varying efficacy and tolerability profiles, with some agents having a higher incidence of gastrointestinal side effects 5, 6
- Head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options for reducing A1C, but differences exist in terms of magnitude of effect on A1C and weight, as well as frequency and severity of adverse effects 6