Byetta side effects
In Byetta's FDA label (revised Sep 2, 2025), the most common side effects were nausea (41% vs 8% on placebo), diarrhea (18% vs 8%) and vomiting (18% vs 4%).
Source: FDA label on DailyMed (Astrazeneca Pharmaceuticals LP), revised , version 26. Read every day: a new FDA version updates this page by itself.
How often Byetta side effects happened
Table 5: Treatment-Emergent Adverse Reactions ≥2% Incidence with BYETTA used with Insulin Glargine with or without Oral Antihyperglycemic Medications (excluding Hypoglycemia)In a 30-week placebo-controlled clinical trial.
| Side effect | Byetta All BYETTA BID | Placebo |
|---|---|---|
| Nausea | 41% | 8% |
| Diarrhea | 18% | 8% |
| Vomiting | 18% | 4% |
| Headache | 14% | 4% |
| Constipation | 10% | 2% |
| Indigestion | 7% | 2% |
| Bloating | 4% | 1% |
| Decreased appetite | 3% | 0% |
| Reflux | 2% | 1% |
| Gas | 2% | 1% |
People in the trial reporting each side effect, as FDA prints it. The placebo column is the rate among people given no medication, which is why a side effect can be common on both.
What the label warns about
Section 5 of the label, word for word.
Acute Pancreatitis
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists, including BYETTA [see Adverse Reactions (6.2)] . After initiation of BYETTA, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue BYETTA and initiate appropriate management.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Never Share a BYETTA Pen Between Patients
BYETTA pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin
Patients receiving BYETTA in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia including severe hypoglycemia [see Adverse Reactions (6) and Drug Interactions (7)] .
The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Acute Kidney Injury Due to Volume Depletion
There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists, BYETTA [see Adverse Reactions (6.2)] . The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea [see Adverse Reactions (6)] . Monitor renal function in patients reporting adverse reactions to BYETTA that could lead to volume depletion, especially during dosage initiation and escalation of BYETTA.
BYETTA is not recommended in patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease and should be used with caution in patients with renal transplantation [see Use in Specific Populations (8.6)] .
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Severe Gastrointestinal Adverse Reactions
Use of GLP-1 receptor agonists, including BYETTA, has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions (6)] . BYETTA is not recommended in patients with severe gastroparesis.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Immunogenicity
Patients may develop antibodies to exenatide following treatment with BYETTA. Antibody levels were measured in 90% of subjects in the 30-week, 24-week, and 16-week placebo-controlled studies and the 30-week comparator-controlled study of BYETTA. In 3%, 4%, 1%, and 1% of these patients, respectively, antibody formation was associated with an attenuated glycemic response. If there is worsening glycemic control or failure to achieve targeted glycemic control, alternative antidiabetic therapy should be considered [see Adverse Reactions (6.1)] .
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Hypersensitivity
There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) in patients treated with BYETTA. If a hypersensitivity reaction occurs, the patient should discontinue BYETTA and other suspect medications and promptly seek medical advice. Inform and closely monitor patients with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist for allergic reactions, because it is unknown whether such patients will be predisposed to anaphylaxis with BYETTA [see Adverse Reactions (6.2)] .
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Drug-Induced Thrombocytopenia
Serious bleeding, which may be fatal, from drug-induced immune-mediated thrombocytopenia has been reported in the postmarketing setting with exenatide use. Drug-induced thrombocytopenia is an immune-mediated reaction, with exenatide-dependent anti-platelet antibodies. In the presence of exenatide, these antibodies cause platelet destruction. If drug-induced thrombocytopenia is suspected, discontinue BYETTA immediately and do not re-expose the patient to exenatide [see Adverse Reactions (6.2)] .
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Acute Gallbladder Disease
Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In a clinical study with exenatide, 1.9% of exenatide-treated patients and 1.4% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Pulmonary Aspiration During General Anesthesia or Deep Sedation
BYETTA delays gastric emptying [see Clinical Pharmacology (12.2) ]. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.
Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking BYETTA, including whether modifying preoperative fasting recommendations or temporarily discontinuing BYETTA could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking BYETTA.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Who should not take Byetta
BYETTA is contraindicated in patients with:
- A prior severe hypersensitivity reaction to exenatide or to any of the excipients in BYETTA. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with BYETTA [see Warnings and Precautions (5.7)].
- A history of drug-induced immune-mediated thrombocytopenia from exenatide products. Serious bleeding, which may be fatal, from drug-induced immune-mediated thrombocytopenia has been reported with exenatide use [see Warnings and Precautions (5.8)] .
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Byetta, pregnancy and breastfeeding
Pregnancy
Risk Summary
Limited data with BYETTA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Based on animal reproduction studies, there may be risks to the fetus from exposure to BYETTA during pregnancy. BYETTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Animal reproduction studies identified increased adverse fetal and neonatal outcomes from exposure to exenatide during pregnancy and lactation in association with maternal effects. In mice, exenatide administered during gestation and lactation caused increased neonatal deaths at systemic exposure 3-times the human exposure resulting from the maximum recommended human dose (MRHD) of 20 mcg/day for BYETTA (see Data) .
The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryofetal risk
Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
Data
Animal Data
In studies evaluating reproduction and development in pregnant mice and rabbits, maternal animals were administered exenatide, the active ingredient in BYETTA, by subcutaneous injection twice a day.
In pregnant mice given 6, 68, 460, or 760 mcg/kg/day exenatide during fetal organogenesis, skeletal variations associated with slowed fetal growth, including changes in number of rib pairs or vertebral ossifications sites, and wavy ribs were observed at 760 mcg/kg/day, a dose that produced maternal toxicity and yielded systemic exposure 390-times the human exposure resulting from the MRHD of BYETTA based on AUC comparison.
In pregnant rabbits given 0.2, 2, 22, 156, or 260 mcg/kg/day exenatide during fetal organogenesis, irregular fetal skeletal ossifications were observed at 2 mcg/kg/day, a dose yielding systemic exposure up to 12-times the human exposure from the MRHD of BYETTA based on AUC comparison.
In maternal mice given 6, 68, or 760 mcg/kg/day exenatide from gestation day 6 through lactation day 20 (weaning), an increased number of neonatal deaths was observed on postpartum days 2 to 4 in dams given 6 mcg/kg/day, a dose yielding a systemic exposure 3-times the human exposure from the MRHD of BYETTA based on AUC comparison.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
Breastfeeding
Risk Summary
There is no information regarding the presence of BYETTA, in human milk, the effects of BYETTA on the breastfed infant, or the effects of BYETTA on milk production. Exenatide was present in the milk of lactating mice. However, due to species-specific differences in lactation physiology, the clinical relevance of these data is not clear (see Data) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BYETTA and any potential adverse effects on the breastfed child from BYETTA or from the underlying maternal condition.
Data
In lactating mice subcutaneously injected twice a day with exenatide, the concentration of exenatide in milk was up to 2.5% of the concentration in maternal plasma.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
What Byetta interacts with
Generic Section
| Table 6: Clinically Relevant Interactions with BYETTA | Table 6: Clinically Relevant Interactions with BYETTA |
|---|---|
| Concomitant Use of Insulin Secretagogues or Insulin | Concomitant Use of Insulin Secretagogues or Insulin |
| Clinical Impact | Exenatide promotes insulin release from pancreatic beta-cells in the presence of elevated glucose concentrations. The risk of hypoglycemia is increased when exenatide is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin [see Warnings and Precautions (5.3) and Adverse Reactions (6)] . |
| Intervention | When initiating BYETTA, consider reducing the dose of concomitantly administered insulin secretagogue or insulin to reduce the risk of hypoglycemia. |
| Warfarin | Warfarin |
| Clinical Impact | In a drug interaction study, BYETTA did not have a significant effect on INR [see Clinical Pharmacology (12.3)] . There have been postmarketing reports for BYETTA of increased INR with concomitant use of warfarin, sometimes associated with bleeding [see Adverse Reactions (6.2) ] . |
| Intervention | In patients taking warfarin, the prothrombin time should be monitored more frequently after initiation or alteration of BYETTA therapy. Once a stable prothrombin time has been documented, the prothrombin time can be monitored at the intervals recommended for patients taking warfarin. |
| Orally Administered Drugs (e.g., acetaminophen) | Orally Administered Drugs (e.g., acetaminophen) |
| Clinical Impact | Exenatide slows gastric emptying. Therefore, BYETTA has the potential to reduce the rate of absorption of orally administered drugs [see Clinical Pharmacology (12.3)]. |
| Intervention | Use caution when administering oral medications with BYETTA where a slower rate of oral absorption may be clinically meaningful. For oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before BYETTA injection. If such drugs are to be administered with food, patients should be advised to take them with a meal or snack when BYETTA is not administered [see Clinical Pharmacology (12.3)] . |
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
All side-effect tables and trial data in the label
Everything the label reports under adverse reactions, in its own order.
The following serious adverse reactions are described below or elsewhere in the prescribing information:
- Acute Pancreatitis [see Warnings and Precautions (5.1)]
- Never Share a BYETTA Pen Between Patients [see Warnings and Precautions (5.2)]
- Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin [see Warnings and Precautions (5.3)]
- Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions (5.4)]
- Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.5)]
- Immunogenicity [see Warnings and Precautions (5.6)]
- Hypersensitivity [see Warnings and Precautions (5.7)]
- Drug-Induced Thrombocytopenia [see Warnings and Precautions (5.8)]
- Acute Gallbladder Disease [see Warnings and Precautions (5.9)]
- Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions (5.10)]
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Hypoglycemia
Table 1 summarizes the incidence and rate of hypoglycemia with BYETTA in six placebo-controlled clinical trials.
| Placebo BID | BYETTA 5 mcg BID | BYETTA 10 mcg BID | |
| Monotherapy (24 Weeks) | Monotherapy (24 Weeks) | Monotherapy (24 Weeks) | Monotherapy (24 Weeks) |
| N | 77 | 77 | 78 |
| % Overall | 1.3% | 5.2% | 3.8% |
| Rate (episodes/patient-year) | 0.03 | 0.21 | 0.52 |
| % Severe | 0.0% | 0.0% | 0.0% |
| With Metformin (30 Weeks) | With Metformin (30 Weeks) | With Metformin (30 Weeks) | With Metformin (30 Weeks) |
| N | 113 | 110 | 113 |
| % Overall | 5.3% | 4.5% | 5.3% |
| Rate (episodes/patient-year) | 0.12 | 0.13 | 0.12 |
| % Severe | 0.0% | 0.0% | 0.0% |
| With a Sulfonylurea (30 Weeks) | With a Sulfonylurea (30 Weeks) | With a Sulfonylurea (30 Weeks) | With a Sulfonylurea (30 Weeks) |
| N | 123 | 125 | 129 |
| % Overall | 3.3% | 14.4% | 35.7% |
| Rate (episodes/patient-year) | 0.07 | 0.64 | 1.61 |
| % Severe | 0.0% | 0.0% | 0.0% |
| With Metformin and a Sulfonylurea (30 Weeks) | With Metformin and a Sulfonylurea (30 Weeks) | With Metformin and a Sulfonylurea (30 Weeks) | With Metformin and a Sulfonylurea (30 Weeks) |
| N | 247 | 245 | 241 |
| % Overall | 12.6% | 19.2% | 27.8% |
| Rate (episodes/patient-year) | 0.58 | 0.78 | 1.71 |
| % Severe | 0.0% | 0.4% | 0.0% |
| With a Thiazolidinedione (16 Weeks) | With a Thiazolidinedione (16 Weeks) | With a Thiazolidinedione (16 Weeks) | With a Thiazolidinedione (16 Weeks) |
| N | 112 | not evaluated | 121 |
| % Overall | 7.1% | not evaluated | 10.7% |
| Rate (episodes/patient-years) | 0.56 | not evaluated | 0.98 |
| % Severe | 0.0% | not evaluated | 0.0% |
| With Insulin Glargine with or without Metformin and/or Thiazolidinedione (30 Weeks) When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA1c ≤8.0% to minimize the risk of hypoglycemia. See Table 9 for insulin dose titration algorithm. | With Insulin Glargine with or without Metformin and/or Thiazolidinedione (30 Weeks) When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA1c ≤8.0% to minimize the risk of hypoglycemia. See Table 9 for insulin dose titration algorithm. | With Insulin Glargine with or without Metformin and/or Thiazolidinedione (30 Weeks) When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA1c ≤8.0% to minimize the risk of hypoglycemia. See Table 9 for insulin dose titration algorithm. | With Insulin Glargine with or without Metformin and/or Thiazolidinedione (30 Weeks) When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA1c ≤8.0% to minimize the risk of hypoglycemia. See Table 9 for insulin dose titration algorithm. |
| N | 122 | not evaluated | 137 |
| % Overall | 29.5% | not evaluated | 24.8% |
| Rate (episodes/patient-years) | 1.58 | not evaluated | 1.61 |
| % Severe | 0.8% | not evaluated | 0.0% |
| N = number of Intent-to-Treat subjects in each treatment group. | N = number of Intent-to-Treat subjects in each treatment group. | N = number of Intent-to-Treat subjects in each treatment group. | N = number of Intent-to-Treat subjects in each treatment group. |
Immunogenicity
Antibodies were assessed in 90% of subjects in the 30-week, 24-week, and 16-week studies of BYETTA. In the 30-week controlled trials of BYETTA add-on to metformin and/or sulfonylurea, antibodies were assessed at 2- to 6-week intervals. The mean antibody titer peaked at Week 6 and was reduced by 55% by Week 30. Three hundred and sixty patients (38%) had low titer antibodies (<625) to exenatide at 30 weeks. The level of glycemic control (HbA 1c ) in these patients was generally comparable to that observed in the 534 patients (56%) without antibody titers. An additional 59 patients (6%) had higher titer antibodies (≥625) at 30 weeks. Of these patients, 32 (3% overall) had an attenuated glycemic response to BYETTA; the remaining 27 (3% overall) had a glycemic response comparable to that of patients without antibodies.
In the 16-week trial of BYETTA add-on to thiazolidinediones, with or without metformin, 36 patients (31%) had low titer antibodies to exenatide at 16 weeks. The level of glycemic control in these patients was generally comparable to that observed in the 69 patients (60%) without antibody titer. An additional 10 patients (9%) had higher titer antibodies at 16 weeks. Of these patients, 4 (4% overall) had an attenuated glycemic response to BYETTA; the remaining 6 (5% overall) had a glycemic response comparable to that of patients without antibodies.
In the 24-week trial of BYETTA used as monotherapy, 40 patients (28%) had low titer antibodies to exenatide at 24 weeks. The level of glycemic control in these patients was generally comparable to that observed in the 101 patients (70%) without antibody titers. An additional 3 patients (2%) had higher titer antibodies at 24 weeks. Of these patients, 1 (1% overall) had an attenuated glycemic response to BYETTA; the remaining 2 (1% overall) had a glycemic response comparable to that of patients without antibodies.
Antibodies to exenatide were not assessed in the 30-week placebo-controlled trial of BYETTA used in combination with insulin glargine.
In the 30-week comparator-controlled trial of BYETTA used in combination with insulin glargine and metformin, 60 patients (20%) had low titer antibodies to exenatide at 30 weeks. The level of glycemic control in these patients was generally comparable to that observed in the 234 patients (77%) without antibody titers. An additional 10 patients (3%) had higher titer antibodies at 30 weeks. Of these patients, 2 (1% overall) had an attenuated glycemic response to BYETTA; the remaining 8 (3% overall) had a glycemic response comparable to that of patients without antibodies.
Two hundred and ten patients with antibodies to exenatide in the BYETTA clinical trials were tested for the presence of cross-reactive antibodies to GLP-1 and/or glucagon. No treatment-emergent cross-reactive antibodies were observed across the range of titers.
Other Adverse Reactions
Monotherapy
For the 24-week placebo-controlled study of BYETTA used as a monotherapy, Table 2 summarizes adverse reactions (excluding hypoglycemia) occurring with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients.
| Monotherapy | Placebo BID N=77 % | All BYETTA BID N=155 % |
|---|---|---|
| Nausea | 0 | 8 |
| Vomiting | 0 | 4 |
| Dyspepsia | 0 | 3 |
| BID = twice daily. | BID = twice daily. | BID = twice daily. |
Adverse reactions reported in ≥1.0% to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite, diarrhea, and dizziness. The most frequently reported adverse reaction associated with BYETTA, nausea, occurred in a dose-dependent fashion.
Two of the 155 patients treated with BYETTA withdrew due to adverse reactions of headache and nausea. No placebo-treated patients withdrew due to adverse reactions.
Cholelithiasis and cholecystitis
In a clinical study with exenatide, 1.9% of exenatide-treated patients and 1.4% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis.
Combination Therapy
Add-On to Metformin and/or Sulfonylurea
In the three 30-week controlled trials of BYETTA add-on to metformin and/or sulfonylurea, adverse reactions (excluding hypoglycemia) with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients are summarized in Table 3.
| Placebo BID N=483 % | All BYETTA BID N=963 % | |
|---|---|---|
| Nausea | 18 | 44 |
| Vomiting | 4 | 13 |
| Diarrhea | 6 | 13 |
| Feeling Jittery | 4 | 9 |
| Dizziness | 6 | 9 |
| Headache | 6 | 9 |
| Dyspepsia | 3 | 6 |
| Asthenia | 2 | 4 |
| Gastroesophageal Reflux Disease | 1 | 3 |
| Hyperhidrosis | 1 | 3 |
| BID = twice daily | BID = twice daily | BID = twice daily |
Adverse reactions reported in ≥1.0% to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite. Nausea was the most frequently reported adverse reaction and occurred in a dose-dependent fashion. With continued therapy, the frequency and severity decreased over time in most of the patients who initially experienced nausea. Patients in the long-term uncontrolled open-label extension studies at 52 weeks reported no new types of adverse reactions than those observed in the 30-week controlled trials.
The most common adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (3% of patients) and vomiting (1%). For placebo-treated patients, <1% withdrew due to nausea and none due to vomiting.
Add-On to Thiazolidinedione with or without Metformin
For the 16-week placebo-controlled study of BYETTA add-on to a thiazolidinedione, with or without metformin, Table 4 summarizes the adverse reactions (excluding hypoglycemia) with an incidence of ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients.
| With a TZD or TZD/MET | Placebo N=112 % | All BYETTA BID N=121 % |
|---|---|---|
| Nausea | 15 | 40 |
| Vomiting | 1 | 13 |
| Dyspepsia | 1 | 7 |
| Diarrhea | 3 | 6 |
| Gastroesophageal Reflux Disease | 0 | 3 |
| BID = twice daily. | BID = twice daily. | BID = twice daily. |
Adverse reactions reported in ≥1.0% to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite. Chills (n=4) and injection-site reactions (n=2) occurred only in BYETTA-treated patients. The two patients who reported an injection-site reaction had high titers of antibodies to exenatide. Two serious adverse events (chest pain and chronic hypersensitivity pneumonitis) were reported in the BYETTA arm. No serious adverse events were reported in the placebo arm.
The most common adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (9%) and vomiting (5%). For placebo-treated patients, <1% withdrew due to nausea.
Add-On to Insulin Glargine with or without Metformin and/or Thiazolidinedione (Placebo-Controlled)
For the 30-week placebo-controlled study of BYETTA as add-on to insulin glargine with or without oral antihyperglycemic medications, Table 5 summarizes adverse reactions (excluding hypoglycemia) occurring with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients.
| With Insulin Glargine | Placebo N=122 % | All BYETTA BID N=137 % |
|---|---|---|
| Nausea | 8 | 41 |
| Vomiting | 4 | 18 |
| Diarrhea | 8 | 18 |
| Headache | 4 | 14 |
| Constipation | 2 | 10 |
| Dyspepsia | 2 | 7 |
| Asthenia | 1 | 5 |
| Abdominal Distension | 1 | 4 |
| Decreased Appetite | 0 | 3 |
| Flatulence | 1 | 2 |
| Gastroesophageal Reflux Disease | 1 | 2 |
| BID = twice daily. | BID = twice daily. | BID = twice daily. |
The most frequently reported adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (5.1%) and vomiting (2.9%). No placebo-treated patients withdrew due to nausea or vomiting.
Postmarketing Experience
The following additional adverse reactions have been reported during post approval use of BYETTA or other formulations of exenatide. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood : Drug induced thrombocytopenia.
Drug Interactions : International normalized ratio (INR) increased with concomitant warfarin use sometimes associated with bleeding [see Drug Interactions (7)] .
Gastrointestinal : Nausea, vomiting, and/or diarrhea resulting in dehydration; abdominal distension, abdominal pain, eructation, constipation, flatulence, ileus, acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death
Hepatobiliary : Cholecystitis, cholelithiasis requiring cholecystectomy.
Hypersensitivity : Injection-site reactions, generalized pruritus and/or urticaria, macular or papular rash, angioedema, anaphylactic reaction.
Neurologic : Dysgeusia, somnolence, dysesthesia.
Pulmonary : Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation.
Renal : Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure or acute renal failure (sometimes requiring hemodialysis), kidney transplant, and kidney transplant dysfunction.
Skin and Subcutaneous Tissue : Alopecia.
Source: Byetta prescribing information (FDA label on DailyMed), revised 2025-09-02
What changed for Exenatide
- RecallRecall: Exenatide Injection, USP, 250 mcg/mL, 1.2 mL per prefilled pen
- FDA labelFDA label updated: Exenatide (Amneal Pharmaceuticals LLC), effective 2026-05-27
- FDAFDA approved a labeling supplement for Byetta
- FDAFDA approved a labeling supplement for Bydureon
- FDAFDA approved a labeling supplement for Bydureon Bcise
- FDAFDA approved a labeling supplement for Byetta
Written from each source's own record as it changes. Every change on GLPcompare
What people have reported to FDA about Byetta
52,087 reports name Byetta, 14,028 of them marked serious, in FDA's file of Oct 28, 2026. Anyone can file a report and a report names every medicine the person took, so these counts cannot show that Byetta caused a problem or how often it happens. For how often, use the trial rates above.
Symptoms reported most
- Blood glucose increased15,615
- Weight decreased12,195
- Nausea12,076
- Decreased appetite5,659
- Blood glucose decreased5,557
- Vomiting4,327
- Diarrhea2,747
- Dizziness2,676
- Headache2,091
- Injection site pain2,042
- Pancreatitis2,004
- Injection site bruising1,857
Pen, dose and use problems reported most
- Drug ineffective2,259
- Incorrect dose administered1,636
- Off label use1,104
- Drug dose omission913
- Product quality issue793
Counted through openFDA from FDA's Adverse Event Reporting System. One report can list several problems.
Byetta side effects: common questions
What are the most common side effects of Byetta?
In Byetta's FDA label (revised Sep 2, 2025), the most common side effects were nausea (41% vs 8% on placebo), diarrhea (18% vs 8%) and vomiting (18% vs 4%). These come from FDA's table of placebo-controlled trials (Table 5: Treatment-Emergent Adverse Reactions ≥2% Incidence with BYETTA used with Insulin Glargine with or without Oral Antihyperglycemic Medications (excluding Hypoglycemia)In a 30-week placebo-controlled clinical trial.).
Does Byetta cause acid reflux?
In its FDA label, 2% of people taking Byetta reported acid reflux, against 1% on placebo.
Does Byetta cause headaches?
In its FDA label, 14% of people taking Byetta reported headaches, against 4% on placebo.
Does Byetta cause constipation?
In its FDA label, 10% of people taking Byetta reported constipation, against 2% on placebo.
Does Byetta cause gas?
In its FDA label, 2% of people taking Byetta reported gas, against 1% on placebo.
Does Byetta cause hair loss?
Its FDA label lists alopecia among side effects reported after approval, without a rate: reports like these come from people using it in practice, so they cannot say how often it happens or prove the medicine caused it.
What serious side effects does the Byetta label warn about?
Its Warnings and Precautions section covers Acute Pancreatitis; Never Share a BYETTA Pen Between Patients; Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin; Acute Kidney Injury Due to Volume Depletion; Severe Gastrointestinal Adverse Reactions; Immunogenicity; Hypersensitivity; Drug-Induced Thrombocytopenia; Acute Gallbladder Disease; and Pulmonary Aspiration During General Anesthesia or Deep Sedation.
Does Byetta have a boxed warning?
No boxed warning appears in Byetta's current FDA label.
Can you take Byetta while pregnant?
Limited data with BYETTA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage.
Can you take Byetta while breastfeeding?
There is no information regarding the presence of BYETTA, in human milk, the effects of BYETTA on the breastfed infant, or the effects of BYETTA on milk production.
Should you stop Byetta before surgery?
Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking BYETTA, including whether modifying preoperative fasting recommendations or temporarily discontinuing BYETTA could reduce the incidence of retained gastric contents.
Does Byetta cause withdrawal symptoms?
The warnings and side effect sections of its FDA label do not list any. What trials do show after people stop a GLP-1 is weight coming back. What happens when you stop a GLP-1
Who should not take Byetta?
BYETTA is contraindicated in patients with: A prior severe hypersensitivity reaction to exenatide or to any of the excipients in BYETTA. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with BYETTA. A history of drug-induced immune-mediated thrombocytopenia from exenatide products. Serious bleeding, which may be fatal, from drug-induced immune-mediated thrombocytopenia has been reported with exenatide use.
How many side effect reports has FDA received about Byetta?
FDA's adverse event system holds 52,087 reports that name Byetta, 14,028 of them marked serious. The most reported symptoms are blood glucose increased, weight decreased, nausea. Anyone can file a report and a report names every medicine the person took, so these cannot show that Byetta caused a problem or how often it happens. The trial rates in its label do that.
Trial rates describe groups, not what one person will feel. Talk to your clinician before starting, stopping or changing a medicine. Label revised Sep 2, 2025.