Trulicity Side Effects and Safety Tips for Patients

Trulicity (dulaglutide) is a once-weekly injectable medication primarily used to help control blood sugar levels in individuals aged 10 years and older with type 2 diabetes. It belongs to a class of drugs called GLP-1 receptor agonists, which work by mimicking the effects of a natural hormone that helps regulate blood sugar, especially after meals.

Clinical studies indicate that Trulicity can reduce HbA1c levels by approximately 0.7% to 1.6% over an average period of 24 to 26 weeks. While Trulicity is effective for many, it may cause side effects, which can vary in both frequency and severity.

In this article, we’ll explore the range of Trulicity side effects, factors that may increase risks, and safety tips for those considering or currently using Trulicity.

Common Side Effects of Trulicity

In clinical trials, Trulicity commonly caused the following side effects:

• • Nausea
  • Diarrhea
  • Vomiting
  • Abdominal pain
  • Decreased appetite
  • Fatigue
  • Indigestion

These side effects were more pronounced during the initial stage of treatment. For instance, nausea was reported in 12.4% of patients on the 0.75 mg dose, increasing to 21.1% at the 1.5 mg dose. However, among participants who continued treatment for up to 36 weeks, the occurrence of common side effects tended to decrease, indicating they may subside over time.

For example, nausea decreased to 16.4% at the 4.5 mg dose, and only 2.6% of patients experienced indigestion at this dose—similar to the percentage of patients in the placebo group at the start of the trial.

In pediatric patients, Trulicity showed a safety profile similar to that observed in adults. However, one notable difference was a higher incidence of injection site reactions, reported in 3.9% of patients on the 0.75 mg dose and 3.8% on the 1.5 mg dose, compared to 2.0% in the placebo group.

For gastrointestinal side effects, the following strategies may help:

Physical habits are equally important. Incorporating light exercise, such as walking, and maintaining a regular sleep schedule can help combat fatigue.

Serious Trulicity Side Effects

Some may experience more severe side effects to Trulicity, such as:

1. Hypoglycemia (with Concomitant Insulin Use)

The risk of hypoglycemia with Trulicity is not dose-dependent but increases when used alongside insulin or insulin secretagogues (such as sulfonylureas).

In clinical trials, all cases of severe hypoglycemia with Trulicity occurred in patients who were also taking sulfonylureas or insulin. However, these episodes are relatively uncommon, occurring in approximately 0.2% of patients over one to two years. Adjusting the doses of insulin or sulfonylureas can help reduce this risk.

Symptoms of hypoglycemia include:

• • Shakiness
  • Sweating
  • Confusion
  • Loss of consciousness (in severe cases)

To help minimize this risk, patients are advised to regularly monitor their blood sugar levels, especially after meals and before bedtime. They may also benefit from carrying a glucose source, like glucose tablets or sugary snacks, for immediate use if symptoms arise.

It’s also recommended that patients inform their healthcare provider of any instances of low blood sugar so that their treatment plan can be adjusted as needed.

2. Hypersensitivity Reactions

Reports of serious allergic reactions, such as anaphylaxis and angioedema, among Trulicity users have been reported. Anaphylaxis is a life-threatening reaction that may cause symptoms such as:

• • Difficulty breathing
  • Swelling of the throat or tongue
  • Rapid heart rate
  • Low blood pressure

Angioedema typically involves swelling under the skin, often around the face, lips, or throat, which can also obstruct breathing.

Patients with a history of hypersensitivity to GLP-1 RAs should exercise caution, as they may have an increased risk. Signs of hypersensitivity, such as rash, hives, swelling, or difficulty breathing, require immediate medical attention, and Trulicity should be discontinued if a serious reaction occurs.

Long-Term Trulicity Side Effects and Considerations

There are also long-term considerations associated with Trulicity use, especially in individuals using the medication over extended periods. These may include:

1. Risk of Thyroid C-cell Tumors

Trulicity carries a boxed warning for the risk of thyroid C-cell tumors. This is based on studies in rodents, which showed an increased production of calcitonin (a hormone produced by C-cells) and abnormal cell growth. However, in humans and certain monkeys, the GLP-1 RA didn’t trigger the same cellular responses as it did in rodents. Even after giving monkeys high doses for 20 months, there were no signs of abnormal cell growth.

Though this risk has not been confirmed in humans, recent studies indicate an increased risk of thyroid cancer with GLP-1 RAs, particularly after one to three years of treatment. Patients should be aware of thyroid tumor symptoms, including:

• • A lump in the neck
  • Trouble swallowing
  • Persistent hoarseness
  • Difficulty breathing

The boxed warning also advises against using Trulicity in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).

2. Pancreatitis

Pancreatitis has been observed in patients taking Trulicity. In one case, a 37-year-old male with type 2 diabetes had been on a weekly dose of 0.75 mg Trulicity for two years, with an increase to 1.5 mg two months before symptom onset.

His tests showed elevated pancreatic enzyme levels, and a CT scan confirmed fat stranding around the pancreas, indicating pancreatitis. The patient’s symptoms of abdominal pain, nausea, and vomiting began shortly after his most recent dose of Trulicity, suggesting a possible link between the increased dose and pancreatitis onset.

If pancreatitis is suspected, Trulicity should be discontinued, and alternative treatments should be considered, especially for patients with a history of pancreatitis.

3. Diabetic Retinopathy Complications

A study following patients with type 2 diabetes and cardiovascular disease or risk factors over 5.4 years found that diabetic retinopathy complications occurred in 1.9% of Trulicity users, compared to 1.5% in those given a placebo.

The risk was notably higher for patients who already had diabetic retinopathy at the start of the study, with complications affecting 8.5% of Trulicity users versus 6.2% of the placebo group. Additionally, rapid improvements in blood sugar control, such as those achieved with Trulicity, are known to temporarily worsen diabetic retinopathy.

For this reason, patients with a history of diabetic retinopathy should be closely monitored when starting or adjusting Trulicity treatment.

4. Acute Gallbladder Disease

In studies and real-world reports, some patients taking Trulicity have experienced gallbladder problems, such as gallstones (cholelithiasis) or gallbladder inflammation (cholecystitis).

Gallstones occurred at a rate of 0.62 per 100 patient-years in Trulicity users, compared to 0.56 per 100 patient-years in those on placebo. Additionally, serious cases of gallbladder inflammation occurred in 0.5% of Trulicity users versus 0.3% in the placebo group.

In a specific case report, a 72-year-old man with type 2 diabetes began taking dulaglutide alongside his other diabetes medications, including metformin, glipizide, pioglitazone, and insulin. After 16 months on dulaglutide, he developed symptoms including:

• • Nausea
  • Loss of appetite
  • Severe, localized pain in the upper right abdomen

Tests confirmed acute cholecystitis, and surgery revealed a severely damaged gallbladder, which was removed. Following the surgery, dulaglutide therapy was resumed without further issues. At an 8-month follow-up, the patient showed no signs of new bile stones, biliary tract disease, or abdominal symptoms.

If a patient on Trulicity shows symptoms of gallstones, doctors should perform gallbladder tests and provide appropriate follow-up care.

5. Severe Gastrointestinal Disease

Chronic gastrointestinal issues or worsening of preexisting GI conditions, such as gastroparesis, can become more evident with long-term use of dulaglutide. In one case, a 57-year-old woman with a 16-year history of type 2 diabetes began experiencing symptoms like abdominal bloating, nausea, and vomiting after 15 months of weekly dulaglutide injections.

Previous upper endoscopy and colonoscopy results showed no obstructions or abnormalities, but a gastric emptying scintigraphy (GES)—a specialized test assessing stomach function—had not been performed. Upon conducting a GES, it was found that 35% of the isotope remained in her stomach after four hours, indicating delayed gastric emptying (gastroparesis).

To address her symptoms, dulaglutide was discontinued for four weeks, leading to a gradual resolution of symptoms. A repeat GES confirmed that her gastric emptying had normalized.

For patients on Trulicity, consider evaluating gastric motility, particularly in those with a history of GI conditions. In cases of delayed gastric emptying, temporary discontinuation of dulaglutide may help resolve symptoms, with follow-up testing recommended to assess improvements.

6. Acute Kidney Injury

Postmarketing reports have documented cases of acute kidney failure and worsening of chronic kidney disease in patients treated with GLP-1 RAs, including Trulicity. Some incidents occurred even in patients without preexisting kidney disease.

Most of these cases involved patients who had experienced side effects that can further stress kidney function, such as:

• • Nausea
  • Vomiting
  • Diarrhea
  • Dehydration

To minimize these risks, ensure adequate fluid intake to avoid dehydration and be alert for symptoms that might suggest kidney problems, including:

• • Reduced urination
  • Swelling in the legs or ankles
  • Fatigue
  • Changes in mental clarity

Caution is advised in patients with renal impairment. Renal function should be closely monitored in these patients, especially if they report severe gastrointestinal symptoms.

Takeaway

Trulicity offers effective blood sugar control for individuals with type 2 diabetes, but users should be aware of both common and serious side effects. Gastrointestinal symptoms such as nausea and diarrhea are most frequent in the early stages of treatment and often decrease over time. However, there are also more severe risks, such as hypoglycemia, thyroid tumors, pancreatitis, and gallbladder issues, which require immediate medical attention.

Patients should also be mindful of kidney health, as dehydration and gastrointestinal issues can strain kidney function. Monitoring symptoms closely and communicating with healthcare providers about any side effects is essential, especially for those with preexisting conditions.

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