{"id": "b040f965-1185-4435-9322-a094664627b5", "subject": "semaglutide", "predicate": "has_boxed_warning", "object": "WARNING: RISK OF THYROID C-CELL TUMORS \u2022 In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13.1 )] . \u2022 WEGOVY is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindications ( 4 )] . Counsel patients regarding the potential risk for MTC with the use of WEGOVY and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with WEGOVY [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. \u2022 In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. ( 5.1 , 13.1 ) \u2022 WEGOVY is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors. ( 4 , 5.1 )", "confidence": 1.0, "source_class": 0, "source_metadata": {"type": "openfda_label", "set_id": "ee06186f-2aa3-4990-a760-757579d8f77b", "section": "boxed_warning", "effective_date": "20251222", "brand_name": "WEGOVY"}, "timestamp": 1770186231}
{"id": "e5d24560-d93d-42c0-a856-b932fb03d358", "subject": "semaglutide", "predicate": "has_adverse_reactions_section", "object": "6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: \u2022 Risk of Thyroid C-Cell Tumors [see Warnings and Precautions ( 5.1 )] \u2022 Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] \u2022 Acute Gallbladder Disease [see Warnings and Precautions ( 5.3 )] \u2022 Hypoglycemia [see Warnings and Precautions ( 5.4 )] \u2022 Acute Kidney Injury due to Volume Depletion [see Warnings and Precautions ( 5.5 )] \u2022 Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.6 )] \u2022 Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] \u2022 Diabetic Retinopathy Complications in Patients with Type 2 Diabetes [see Warnings and Precautions ( 5.8 )] \u2022 Heart Rate Increase [see Warnings and Precautions ( 5.9 )] \u2022 Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.10 )] \u2022 Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (incidence \u22655%) in adults or pediatric patients aged 12 years and older are: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc., at 1-833-934-6891 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 studies of another drug and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials in Adults with Obesity or Overweight for Weight Reduction WEGOVY 2.4 mg Subcutaneous Weekly Dosage WEGOVY was evaluated for safety in 3 randomized, double-blind, placebo-controlled trials that included 2,116 adult patients with obesity or overweight treated with 2.4 mg WEGOVY for up to 68 weeks and a 7-week off-drug follow-up period [see Clinical Studies ( 14.2 )] . Baseline characteristics included a mean age of 48 years, 71% female, 72% White, 14% Asian, 9% Black or African American, and 5% reported as other or unknown; and 85% were not Hispanic or Latino ethnicity, 13% were Hispanic or Latino ethnicity, and 2% reported as unknown. The baseline characteristics were 42% with hypertension, 19% with type 2 diabetes, 43% with dyslipidemia, 28% with a BMI greater than 40 kg/m 2 , and 4% with CV disease. In these clinical trials, 6.8% of patients treated with 2.4 mg WEGOVY and 3.2% of patients treated with placebo permanently discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were nausea (1.8% versus 0.2%), vomiting (1.2% versus 0%), and diarrhea (0.7% versus 0.1%) for WEGOVY and placebo, respectively. Adverse reactions reported in clinical trials in adults and greater than or equal to 2% of WEGOVY-treated patients and more frequently than in placebo-treated patients are shown in Table 3 . Table 3. Adverse Reactions (\u22652% and Greater Than Placebo) in WEGOVY Injection-treated Adults with Obesity or Overweight for Weight Reduction Placebo N=1,261 % WEGOVY Injection (2.4 mg once weekly) N=2,116 % Nausea 16 44 Diarrhea 16 30 Vomiting 6 24 Constipation 11 24 Abdominal Pain a 10 20 Headache 10 14 Fatigue b 5 11 Dyspepsia 3 9 Dizziness 4 8 Abdominal Distension 5 7 Eructation <1 7 Hypoglycemia in T2DM c 2 6 Flatulence 4 6 Gastroenteritis 4 6 Gastroesophageal Reflux Disease 3 5 Gastritis d 1 4 Gastroenteritis Viral 3 4 Hair Loss 1 3 Dysesthesia e 1 2 a Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal tenderness, abdominal discomfort and epigastric discomfort b Includes fatigue and asthenia c Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia or severe hypoglycemia (requiring the assistance of another person) in patients with type 2 diabetes not on concomitant insulin (Study 3, WEGOVY N=403, Placebo N=402). See text below for further information regarding hypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus d Includes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis e Includes paresthesia, hyperesthesia, burning sensation, allodynia, dysesthesia, skin burning sensation, pain of skin, and sensitive skin In a CV outcomes trial, 8,803 patients were exposed to WEGOVY injection for a median of 37.3 months and 8,801 patients were exposed to placebo for a median of 38.6 months [see Clinical Studies ( 14.1 )] . Safety data collection was limited to serious adverse events (including death), adverse events leading to discontinuation, and adverse events of special interest. Sixteen percent (16%) of WEGOVY injection-treated patients and 8% of placebo-treated patients, respectively, discontinued study drug due to an adverse event. Additional information from this trial is included in subsequent sections below when relevant. WEGOVY Tablet 25 mg Oral Daily Dosage WEGOVY tablet was evaluated for safety in a randomized, double-blind, placebo-controlled trial that included 204 adult patients with obesity or overweight and at least one weight-related comorbidity, treated with WEGOVY tablet for up to 64 weeks and a 7-week off drug follow-up period (Study 7) [see Clinical Studies ( 14.2 )] . Patients with type 2 diabetes mellitus were excluded. Baseline characteristics included a mean age of 48 years, 75.6% were female, 92.7% were White, 0.5% were Asian, 6.3% were Black or African American, and 8.3% were Hispanic or Latino ethnicity. Mean baseline body weight was 106.4 kg and mean BMI was 37.5 kg/m 2 . The baseline characteristics were 44% with hypertension, 31% with dyslipidemia, 27% with a BMI greater than 40 kg/m 2 , and 1.5% with coronary artery disease. In the clinical trial, 6.9% of patients treated with WEGOVY 25 mg tablets and 5.9% patients treated with placebo permanently discontinued treatment as a result of adverse reactions. The most common event type leading to discontinuation was gastrointestinal adverse reactions reported in 3.4% with WEGOVY tablets and 2% with placebo. In the clinical trial with WEGOVY tablets, the types and frequency of common adverse reactions were similar to those listed in Table 3 . Adverse Reactions in a Clinical Trial of Pediatric Patients Aged 12 Years and Older with Obesity Treated with WEGOVY Injection for Weight Reduction WEGOVY injection was evaluated in a 68-week, double-blind, randomized, parallel group, placebo-controlled, multi-center trial in 201 pediatric patients aged 12 years and older with obesity [see Clinical Studies ( 14.3 )] . Baseline characteristics included a mean age of 15.4 years; 38% of patients were male; 79% were White, 8% were Black or African American, 2% were Asian, and 11% were of other or unknown race; and 11% were of Hispanic or Latino ethnicity. The mean baseline body weight was 107.5 kg, and mean BMI was 37 kg/m 2 . Table 4 shows adverse reactions reported in greater than or equal to 3% of WEGOVY injection-treated pediatric patients and more frequently than in the placebo group from a study in pediatric patients aged 12 years and older. Table 4. Adverse Reactions (\u22653% and Greater than Placebo) in WEGOVY Injection-treated Pediatric Patients Aged 12 Years and Older with Obesity for Weight Reduction Placebo N=67 % WEGOVY Injection (2.4 mg once weekly) N=133 % Nausea 18 42 Vomiting 10 36 Diarrhea 19 22 Headache 16 17 Abdominal Pain 6 15 Nasopharyngitis 10 12 Dizziness 3 8 Gastroenteritis 3 7 Constipation 2 6 Gastroesophageal Reflux Disease 2 4 Sinusitis 2 4 Urinary tract infection 2 4 Ligament sprain 2 4 Anxiety 2 4 Hair Loss 0 4 Cholelithiasis 0 4 Eructation 0 4 Influenza 0 3 Rash 0 3 Urticaria 0 3 Adverse Reactions in Clinical Trials in Adults with MASH Treated with WEGOVY Injection The safety of WEGOVY injection was evaluated in a randomized, double-blind, placebo-controlled trial (Study 9) that included 1,195 adult patients with MASH, including 800 patients who were exposed to WEGOVY for a median of 95.3 weeks and 395 patients who were exposed to placebo for a median of 83.1 weeks [see Clinical Studies ( 14.4 )] . The most commonly reported adverse reactions were consistent with the other approved WEGOVY indications (see Table 3 ). There is limited information in patients with MASH and a BMI <25 kg/m 2 . Additional information from the MASH trial is included in subsequent sections when notable. Unless indicated, the incidence of the adverse reactions in MASH patients was similar to other approved indications. Other Adverse Reactions in Adults and/or Pediatric Patients Treated with WEGOVY Injection or WEGOVY Tablets Acute Gallbladder Disease In WEGOVY clinical trials in adults for weight reduction, cholelithiasis was reported by 1.6% of WEGOVY injection-treated patients and 0.7% of placebo-treated patients and by 2.5% of WEGOVY tablet-treated patients and 1% of placebo tablet-treated patients. Cholecystitis was reported by 0.6% of WEGOVY injection-treated adult patients and 0.2% of placebo-treated patients. In a clinical trial in pediatric patients aged 12 years and older for weight reduction [see Clinical Studies ( 14.3 )] , cholelithiasis was reported by 3.8% of WEGOVY injection-treated patients and 0% placebo-treated patients. Cholecystitis was reported by 0.8% of WEGOVY injection-treated pediatric patients and 0% placebo-treated patients. Hypoglycemia Patients with Type 2 Diabetes In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 for weight reduction, clinically significant hypoglycemia (defined as a plasma glucose less than 54 mg/dL) was reported in 6.2% of WEGOVY injection-treated patients versus 2.5% of placebo-treated patients. A higher rate of clinically significant hypoglycemic episodes was reported with WEGOVY injection (semaglutide 2.4 mg) versus semaglutide 1 mg injection (10.7 vs. 7.2 episodes per 100 patient years of exposure, respectively); the rate in the placebo-treated group was 3.2 episodes per 100 patient years of exposure. In addition, one episode of severe hypoglycemia requiring intravenous glucose was reported in a WEGOVY injection-treated patient versus none in placebo-treated patients. The risk of hypoglycemia was increased when WEGOVY was used with a sulfonylurea. In a glycemic control trial evaluating a dose comparable to the 9 mg dose and the 25 mg semaglutide tablet dose in patients with type 2 diabetes not on insulin, clinically significant hypoglycemia was reported in similar proportions of subjects in both treatment groups. Patients without Type 2 Diabetes Episodes of hypoglycemia have been reported with GLP-1 receptor agonists in adult patients without type 2 diabetes mellitus. In WEGOVY clinical trials in adult patients without type 2 diabetes mellitus for weight reduction, there was no systematic capturing or reporting of hypoglycemia. In a CV outcomes trial in adult patients without type 2 diabetes, 3 episodes of serious hypoglycemia were reported in WEGOVY injection-treated patients versus 1 episode in placebo. Patients with a history of bariatric surgery (a risk factor for hypoglycemia) had more events of serious hypoglycemia while taking WEGOVY injection (2.3%, 2/87) than placebo (0%, 0/97). Retinal Disorders in Patients with Type 2 Diabetes In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 for weight reduction, retinal disorders were reported by 6.9% of patients treated with WEGOVY injection (semaglutide 2.4 mg), 6.2% of patients treated with semaglutide 1 mg, and 4.2% of patients treated with placebo. The majority of events were reported as diabetic retinopathy (4%, 2.7%, and 2.7%, respectively) and non-proliferative retinopathy (0.7%, 0%, and 0%, respectively). In a glycemic control trial evaluating the 9 mg and 25 mg semaglutide tablet doses in patients with type 2 diabetes, a similar proportion of patients in each dose group reported diabetic retinopathy related adverse reactions during the trial; 1.3% and 1.9% of patients in the 9 mg and 25 mg semaglutide group, respectively, reported moderate-severe non-proliferative diabetic retinopathy events, and 0% and 0.4% reported proliferative retinopathy events, respectively. In a 2-year trial with semaglutide 0.5 mg and 1 mg once-weekly injection in adult patients with type 2 diabetes and high cardiovascular risk, diabetic retinopathy complications (which was a 4-component adjudicated endpoint) occurred in patients treated with semaglutide injection (3%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (semaglutide injection 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (semaglutide injection 0.7%, placebo 0.4%). Gastrointestinal Adverse Reactions In clinical trials in adults for weight reduction, 73% of WEGOVY injection-treated patients and 47% of patients receiving placebo reported gastrointestinal adverse reactions, including severe reactions that were reported more frequently among patients receiving WEGOVY injection (4.1%) than placebo (0.9%). The most frequently reported reactions were nausea (44% vs. 16%), vomiting (25% vs. 6%), and diarrhea (30% vs. 16%). Other reactions that occurred at a higher incidence among WEGOVY injection-treated adult patients included dyspepsia, abdominal pain, abdominal distension, eructation, flatulence, gastroesophageal reflux disease, gastritis, hemorrhoids, and hiccups. These reactions were most frequently reported during dosage escalation. Severe gastrointestinal adverse reactions were reported in 2% of WEGOVY tablet-treated and 0% of placebo-treated patients, respectively. In the pediatric clinical trial for weight reduction, 62% of WEGOVY injection-treated patients and 42% of placebo-treated patients reported gastrointestinal adverse reactions. The most frequently reported reactions were nausea (42% vs. 18%), vomiting (36% vs. 10%), and diarrhea (22% vs. 19%). Other gastrointestinal-related reactions that occurred at a higher incidence than placebo among WEGOVY injection-treated pediatric patients included abdominal pain, constipation, eructation, gastroesophageal reflux disease, dyspepsia, and flatulence. Permanent discontinuation of treatment as a result of a gastrointestinal adverse reaction occurred in 4.3% of WEGOVY injection-treated adult patients versus 0.7% of placebo-treated patients. In a pediatric clinical trial for weight reduction, 2.3% of patients treated with WEGOVY injection versus 1.5% of patients who received placebo discontinued treatment as a result of gastrointestinal adverse reactions. Other Adverse Reactions in Adults and/or Pediatric Patients Treated with WEGOVY Injection The below adverse reactions are applicable for both WEGOVY injection and WEGOVY tablets and include descriptions of WEGOVY injection clinical trial data, where relevant. The safety and effectiveness of WEGOVY tablets have not been established in pediatric patients or patients with MASH. Acute Pancreatitis In WEGOVY clinical trials in adults for weight reduction, acute pancreatitis was confirmed by adjudication in 4 WEGOVY-treated patients (0.2 cases per 100 patient years) and 1 in placebo-treated patients (less than 0.1 cases per 100 patient years). One additional case of acute pancreatitis was confirmed in a patient treated with WEGOVY in another clinical trial. Acute Kidney Injury Acute kidney injury occurred in clinical trials for weight reduction in 7 adult patients (0.4 cases per 100 patient years) receiving WEGOVY versus 4 patients (0.2 cases per 100 patient years of exposure) receiving placebo. Some of these adverse reactions occurred in association with gastrointestinal adverse reactions or dehydration. In addition, 2 patients treated with WEGOVY had acute kidney injury with dehydration in other clinical trials. The risk of renal adverse reactions with WEGOVY was increased in adult patients with a history of renal impairment (trials included 65 patients with a history of moderate or severe renal impairment at baseline), and occurred more frequently during dose titration. Increase in Heart Rate Mean increases in resting heart rate of 1 to 4 beats per minute (bpm) were observed with routine clinical monitoring in WEGOVY-treated adult patients compared to placebo in clinical trials for weight reduction. In weight reduction trials in which adult patients were randomized prior to dose-escalation, more patients treated with WEGOVY, compared with placebo, had maximum changes from baseline at any visit of 10 to 19 bpm (41% versus 34%, respectively) and 20 bpm or more (26% versus 16%, respectively). In a clinical trial for weight reduction in pediatric patients aged 12 years and older with normal baseline heart rate, more patients treated with WEGOVY compared to placebo had maximum changes in heart rate of 20 bpm or more (54% versus 39%). Hypotension and Syncope Adverse reactions related to hypotension (hypotension, orthostatic hypotension, and decreased blood pressure) were reported in 1.3% of WEGOVY-treated adult patients versus 0.4% of placebo-treated patients and syncope was reported in 0.8% of WEGOVY-treated patients versus 0.2% of placebo-treated patients in clinical trials for weight reduction. Some reactions were related to gastrointestinal adverse reactions and volume loss associated with WEGOVY. Hypotension and orthostatic hypotension were more frequently seen in patients on concomitant antihypertensive therapy. In a clinical trial in pediatric patients aged 12 years and older for weight reduction, hypotension was reported in 2.3% of WEGOVY-treated patients versus 0% in placebo-treated patients. Appendicitis Appendicitis (including perforated appendicitis) occurred in 10 (0.5%) WEGOVY-treated adult patients and 2 (0.2%) patients receiving placebo in clinical trials for weight reduction. Injection Site Reactions In clinical trials in adults for weight reduction, 1.4% of WEGOVY-treated patients and 1% of patients receiving placebo experienced injection site reactions (including injection site pruritus, erythema, inflammation, induration, and irritation). Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with WEGOVY. In a pediatric clinical trial for weight reduction, rash was reported in 3% of WEGOVY-treated patients and 0% of placebo-treated patients, and urticaria was reported in 3% of WEGOVY-treated patients and 0% of placebo-treated patients . In adult clinical trials for weight reduction, allergic reactions occurred in 16% (8/50) of WEGOVY-treated patients with anti-semaglutide antibodies and in 7% (114/1659) of WEGOVY-treated patients who did not develop anti-semaglutide antibodies [see Clinical Pharmacology ( 12.6 )]. Fractures In the CV outcomes trial in adults, more fractures of the hip and pelvis were reported on WEGOVY than on placebo in female patients: 1% (24/2,448) vs. 0.2% (5/2,424), and in patients ages 75 years and older: 2.4% (17/703) vs. 0.6% (4/663), respectively. In a clinical trial in adults with MASH, fractures occurred in 4.4% of WEGOVY-treated patients (2.6 cases per 100 patient years) compared to 3.3% of placebo-treated patients (2 cases per 100 patient years). Fractures were reported in both males and females with a median age of 61 years (range, 44 to 75). Urolithiasis In a CV outcomes trial, 1.2% of WEGOVY-treated patients and 0.8% of patients receiving placebo reported urolithiasis, including serious reactions that were reported more frequently among patients receiving WEGOVY (0.6%) than placebo (0.4%). Dysgeusia In clinical trials in adults for weight reduction, 1.7% of WEGOVY-treated patients and 0.5% of placebo-treated patients reported dysgeusia. Other Adverse Reactions in Adult Patients Treated with WEGOVY Tablets for Weight Reduction Dysesthesia In a clinical trial with WEGOVY tablets, 4.9% of WEGOVY-treated patients and no placebo-treated patients reported dysesthesia adverse reactions, with preferred terms including sensitive skin, hyperesthesia, paresthesia, allodynia, and skin burning sensation. Laboratory Abnormalities in Adults and/or Pediatric Patients Treated with WEGOVY Injection The below laboratory abnormalities are applicable for both WEGOVY injection and WEGOVY tablets and include descriptions of WEGOVY injection clinical trial data, where relevant. The safety and effectiveness of WEGOVY tablets have not been established in pediatric patients or patients with MASH. Amylase and Lipase Adult and pediatric patients treated with WEGOVY had a mean increase from baseline in amylase of 15% to 16% and lipase of 39% in clinical trials for weight reduction. These changes were not observed in the placebo group. In a clinical trial in adults with MASH, increases in lipase greater than 3 times the upper limit of normal (ULN) occurred in 4.7% (35/750) of WEGOVY-treated patients compared with 1.3% (5/374) of placebo-treated patients. The clinical significance of elevations in lipase or amylase with WEGOVY is unknown in the absence of other signs and symptoms of pancreatitis. Liver Tests In a pediatric clinical trial for weight reduction, increases in alanine aminotransferase (ALT) greater than or equal to 5 times the ULN were observed in 4 (3%) WEGOVY-treated patients compared with 0% of placebo-treated patients. In some patients, increases in ALT and AST were associated with other confounding factors (such as gallstones). In the CV outcomes trial in adults, increases in total bilirubin greater than or equal to 3 times the ULN were observed in 0.3% (30/8,585) of WEGOVY-treated patients versus 0.2% (14/8,579) of placebo-treated patients. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient of WEGOVY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: acute pancreatitis and necrotizing pancreatitis, sometimes resulting in death; ileus, intestinal obstruction, severe constipation including fecal impaction Hypersensitivity: anaphylaxis, angioedema, rash, urticaria Pulmonary: Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation Renal and Urinary Disorders: acute kidney injury", "confidence": 1.0, "source_class": 0, "source_metadata": {"type": "openfda_label", "set_id": "ee06186f-2aa3-4990-a760-757579d8f77b", "section": "adverse_reactions", "effective_date": "20251222", "brand_name": "WEGOVY"}, "timestamp": 1770186231}
{"id": "14fcd829-6698-4740-9b96-6b8b6117ad95", "subject": "tirzepatide", "predicate": "has_boxed_warning", "object": "WARNING: RISK OF THYROID C-CELL TUMORS In rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether ZEPBOUND causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ) and Nonclinical Toxicology ( 13.1 )]. ZEPBOUND is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindications ( 4 )] . Counsel patients regarding the potential risk for MTC with the use of ZEPBOUND and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with ZEPBOUND [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )]. WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. In rats, tirzepatide causes thyroid C-cell tumors. It is unknown whether ZEPBOUND causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined ( 5.1 , 13.1 ). ZEPBOUND is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors ( 4 , 5.1 ).", "confidence": 1.0, "source_class": 0, "source_metadata": {"type": "openfda_label", "set_id": "487cd7e7-434c-4925-99fa-aa80b1cc776b", "section": "boxed_warning", "effective_date": "20260107", "brand_name": "Zepbound"}, "timestamp": 1770186232}
{"id": "45792a1b-bc26-4b3f-b567-205f9f77420f", "subject": "tirzepatide", "predicate": "has_adverse_reactions_section", "object": "6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: Risk of Thyroid C-cell Tumors [see Warnings and Precautions ( 5.1 )] Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.2 )] Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.3 )] Acute Gallbladder Disease [see Warnings and Precautions ( 5.4 )] Acute Pancreatitis [see Warnings and Precautions ( 5.5 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] Hypoglycemia [see Warnings and Precautions ( 5.7 )] Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus [see Warnings and Precautions ( 5.8 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.9 )] Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.10 )] The most common adverse reactions, reported in \u22655% of patients treated with ZEPBOUND are: nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection site reactions, fatigue, hypersensitivity reactions, eructation, hair loss, gastroesophageal reflux disease. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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. Adverse Reactions in Patients for Weight Reduction and Long-Term Maintenance Pool of Placebo - Controlled Weight Reduction Trials in Adults with Obesity or Overweight, with or without Type 2 Diabetes (Study 1 and Study 2) ZEPBOUND was evaluated for safety in a pool of two randomized, double-blind, placebo-controlled trials that included 2,519 adult patients with obesity or overweight treated with ZEPBOUND for up to 72 weeks and a 4-week off drug follow-up period (Study 1 and Study 2) [see Clinical Studies ( 14.1 )] . The mean age of patients was 47 years and 37% were male. The population was 72% White, 12% Asian, 8% Black or African American, and 7% American Indian or Alaska Native; 51% identified as Hispanic or Latino ethnicity. Baseline characteristics included an average BMI of 37.4 kg/m 2 , 29% with a BMI \u226540 kg/m 2 , 41% with hypertension, 37% with dyslipidemia, 25% with type 2 diabetes mellitus, 7% with obstructive sleep apnea, and 4% with cardiovascular disease. Across both trials, 4.8%, 6.3%, and 6.7% of patients treated with 5 mg, 10 mg, and 15 mg of ZEPBOUND, respectively, permanently discontinued treatment as a result of adverse reactions compared to 3.4% of patients treated with placebo. The majority of patients who discontinued ZEPBOUND due to adverse reactions did so during the first few months of treatment due to gastrointestinal adverse reactions. Common Adverse Reactions Table 1 shows common adverse reactions associated with the use of ZEPBOUND in the pool of two placebo-controlled trials for weight reduction (Study 1 and Study 2). These adverse reactions occurred more commonly with ZEPBOUND than with placebo and occurred in at least 2% of patients treated with ZEPBOUND. Table 1: Adverse Reactions (\u22652% and Greater than Placebo) in ZEPBOUND-Treated Adults with Obesity or Overweight in Weight Reduction and Long-term Maintenance Trials (Study 1 and Study 2) a Includes diarrhea, frequent bowel movements. b Includes constipation, feces hard. c Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness. d Includes multiple related adverse event terms, such as injection site bruising, injection site erythema, injection site pruritus, injection site pain, injection site rash, injection site reaction. e Includes asthenia, fatigue, lethargy, malaise. f Includes blood pressure decreased, hypotension, orthostatic hypotension. Adverse Reaction Placebo (N=958) % ZEPBOUND 5 mg (N=630) % ZEPBOUND 10 mg (N=948) % ZEPBOUND 15 mg (N=941) % Nausea 8 25 29 28 Diarrhea a 8 19 21 23 Vomiting 2 8 11 13 Constipation b 5 17 14 11 Abdominal Pain c 5 9 9 10 Dyspepsia 4 9 9 10 Injection Site Reactions d 2 6 8 8 Fatigue e 3 5 6 7 Hypersensitivity Reactions 3 5 5 5 Eructation 1 4 5 5 Hair Loss 1 5 4 5 Gastroesophageal Reflux Disease 2 4 4 5 Flatulence 2 3 3 4 Abdominal Distension 2 3 3 4 Dizziness 2 4 5 4 Hypotension f 0 1 1 2 In a clinical trial for weight reduction that included an intensive lifestyle intervention lead-in period (Study 3), 287 patients were treated with ZEPBOUND for up to 72 weeks. In a randomized withdrawal trial (Study 4), 783 patients were treated with ZEPBOUND for up to 36 weeks, and 335 of these patients were treated for up to 88 weeks [see Clinical Studies ( 14.1 )] . In Study 3, 10% of ZEPBOUND-treated patients and 2% of placebo-treated patients discontinued drug due to adverse reactions. In Study 4, 7% of patients discontinued ZEPBOUND treatment before randomized withdrawal at Week 36 due to adverse reactions. In Study 3 and Study 4, adverse reactions were similar to those reported in the two pooled ZEPBOUND clinical trials (Study 1 and Study 2). Gastrointestinal Adverse Reactions In a pool of Study 1 and 2, gastrointestinal adverse reactions occurred more frequently among patients receiving ZEPBOUND (5 mg 56%, 10 mg 56%, 15 mg 56%) than placebo (30%). More patients receiving ZEPBOUND 5 mg (1.9%), ZEPBOUND 10 mg (3.3%), and ZEPBOUND 15 mg (4.3%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.5%). The majority of nausea, vomiting, and/or diarrhea events occurred during dose escalation and decreased over time. Acute Pancreatitis In clinical trials of tirzepatide for a different indication, 14 events of acute pancreatitis were confirmed by adjudication in 13 tirzepatide-treated patients (0.23 patients per 100 years of exposure) versus 3 events in 3 comparator-treated patients (0.11 patients per 100 years of exposure). In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), 0.2% of ZEPBOUND-treated patients had acute pancreatitis confirmed by adjudication (0.14 patients per 100 years of exposure) versus 0.2% of placebo-treated patients (0.15 patients per 100 years of exposure). The exposure-adjusted incidence rate for treatment-emergent adjudication-confirmed pancreatitis in the pooled clinical studies for OSA (Studies 5 and 6) was 0.84 patients per 100 years for ZEPBOUND and 0 for placebo-treated patients. Hypotension In a pool of Study 1 and 2, hypotension occurred more frequently among patients taking ZEPBOUND (1.6%) than patients taking placebo (0.1%). Hypotension was more frequently seen in ZEPBOUND-treated patients on concomitant antihypertensive therapy (2.2%) compared to ZEPBOUND-treated patients not on antihypertensive therapy (1.2%). Hypotension also occurred in association with gastrointestinal adverse events and dehydration. Hypersensitivity Reactions In a pool of Study 1 and 2, immediate hypersensitivity reactions (within one day after drug administration) occurred in 2.1% of ZEPBOUND-treated patients compared to 0.4% of placebo-treated patients, while non-immediate hypersensitivity reactions occurred in 3.5% of ZEPBOUND-treated patients compared to 2.7% of placebo-treated patients. Among ZEPBOUND-treated patients, hypersensitivity reactions were more frequent in those with anti-tirzepatide antibodies (6.2%) compared to those who did not develop anti-tirzepatide antibodies (3%) [see Clinical Pharmacology ( 12.6 )] . The majority of the hypersensitivity reactions in trials were skin reactions (e.g., rash, itching). Injection Site Reactions In ZEPBOUND-treated patients in a pool of Study 1 and 2, injection site reactions were more frequent in those with anti-tirzepatide antibodies (11.3%) compared to those who did not develop anti-tirzepatide antibodies (1%) [see Clinical Pharmacology ( 12.6 )] . Hair Loss Hair loss adverse reactions in ZEPBOUND-treated patients were associated with weight reduction. In a pool of Study 1 and 2, hair loss was reported more frequently in female than male patients in the ZEPBOUND (7.1% female versus 0.5% male) and placebo (1.3% female versus 0% male) treatment groups. No ZEPBOUND-treated patients and one placebo-treated patient discontinued study treatment due to hair loss. Other Adverse Reactions Acute Kidney Injury In a pool of Study 1 and 2, acute kidney injury was reported in 0.5% of ZEPBOUND-treated patients compared to 0.2% of placebo-treated patients. Acute Gallbladder Disease In a pool of Study 1 and 2, cholelithiasis was reported in 1.1% of ZEPBOUND-treated patients and 1% of placebo-treated patients, cholecystitis was reported in 0.7% of ZEPBOUND-treated patients and 0.2% of placebo-treated patients, and cholecystectomy was reported in 0.2% of ZEPBOUND-treated patients and no placebo-treated patients. Hypoglycemia In Study 2, a trial of patients with type 2 diabetes mellitus and BMI \u226527 kg/m 2 , hypoglycemia (plasma glucose <54 mg/dL) was reported in 4.2% of ZEPBOUND-treated patients versus 1.3% of placebo-treated patients. In Study 1, a trial of ZEPBOUND in adults with obesity/overweight without type 2 diabetes mellitus, there was no systematic capturing of hypoglycemia, but plasma glucose <54 mg/dL was reported in 0.3% of ZEPBOUND-treated patients versus no placebo-treated patients. Heart Rate Increase In a pool of Study 1 and 2, treatment with ZEPBOUND resulted in a mean increase in heart rate of 1 to 3 beats per minute compared to no increase in placebo-treated patients. Dysesthesia In a pool of Study 1 and 2, dysesthesia occurred more frequently among patients receiving ZEPBOUND (5 mg 0.2%, 10 mg 0.2%, 15 mg 0.4%) than placebo (0.1%). Dysgeusia In a pool of Study 1 and 2, dysgeusia was reported by 0.4% of ZEPBOUND-treated patients and no placebo-treated patients. Dry Mouth In a pool of Study 1 and 2, dry mouth or dry throat was reported by 1% of ZEPBOUND-treated patients and 0.1% of placebo-treated patients. Laboratory Abnormalities Amylase and Lipase Increase In a pool of Study 1 and 2, treatment with ZEPBOUND resulted in mean increases from baseline in serum pancreatic amylase concentrations of 20% to 25% and serum lipase concentrations of 28% to 35%, compared to mean increases from baseline in pancreatic amylase of 2.1% and serum lipase of 5.8% in placebo-treated patients. The clinical significance of elevations in amylase or lipase with ZEPBOUND is unknown in the absence of other signs and symptoms of pancreatitis. Adverse Reactions in Patients with Obstructive Sleep Apnea ZEPBOUND was evaluated in 2 randomized, double-blind, placebo-controlled trials (Study 5 and Study 6) that included a total of 467 adult patients with moderate to severe OSA and obesity [see Clinical Studies ( 14.2 )] . Study 5 enrolled 234 patients who were unable or unwilling to use Positive Airway Pressure (PAP) therapy and Study 6 enrolled 235 patients who were on PAP therapy. The adverse reactions observed with ZEPBOUND 10 mg or 15 mg administered subcutaneously once weekly were similar to those reported in the two pooled placebo controlled clinical trials for weight reduction (Study 1 and Study 2). 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of tirzepatide, the active ingredient in ZEPBOUND. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Gastrointestinal: acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus Hypersensitivity: anaphylaxis, angioedema Pulmonary: Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation. Renal: acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis", "confidence": 1.0, "source_class": 0, "source_metadata": {"type": "openfda_label", "set_id": "487cd7e7-434c-4925-99fa-aa80b1cc776b", "section": "adverse_reactions", "effective_date": "20260107", "brand_name": "Zepbound"}, "timestamp": 1770186232}
{"id": "2e28a474-54c2-4561-90e0-eff2d191f4a1", "subject": "liraglutide", "predicate": "has_boxed_warning", "object": "WARNING: RISK OF THYROID C-CELL TUMORS Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13.1 )] . Liraglutide is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of liraglutide and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with liraglutide injection [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. Liraglutide causes thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined ( 5.1 , 13.1 ). Liraglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and the symptoms of thyroid tumors ( 4 , 5.1 ).", "confidence": 1.0, "source_class": 0, "source_metadata": {"type": "openfda_label", "set_id": "0efc3a89-211a-4496-baab-e8265e07de2b", "section": "boxed_warning", "effective_date": "20260130", "brand_name": "Liraglutide"}, "timestamp": 1770186233}
{"id": "c0e36511-be6a-4402-8179-305006deef3f", "subject": "liraglutide", "predicate": "has_adverse_reactions_section", "object": "6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: Risk of Thyroid C-cell Tumors [see Warnings and Precautions ( 5.1 )] Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] Hypoglycemia [see Warnings and Precautions ( 5.4 )] Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.5 )] Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.6 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Acute Gallbladder Disease [see Warnings and Precautions ( 5.8 )] Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (incidence \u22655%) in clinical trials are nausea, diarrhea, vomiting, decreased appetite, dyspepsia, constipation. ( 6.1 ) Immunogenicity-related events, including urticaria, were more common among liraglutide-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials. ( 12.6 ) To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc. at 1-844-824-8426 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials 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. Common Adverse Reactions The safety of liraglutide injection in patients with type 2 diabetes mellitus was evaluated in 5 glycemic control, placebo-controlled trials in adults and one trial of 52 weeks duration in pediatric patients 10 years of age and older [see Clinical Studies ( 14.1 )] . The data in Table 1 reflect exposure of 1,673 adult patients to liraglutide and a mean duration of exposure to liraglutide of 37.3 weeks. The mean age of adult patients was 58 years, 4% were 75 years or older and 54% were male. The population was 79% White, 6% Black or African American, 13% Asian; 4% were of Hispanic or Latino ethnicity. At baseline the population had diabetes for an average of 9 years and a mean HbA 1c of 8.4%. Baseline estimated renal function was normal or mildly impaired in 88% and moderately impaired in 12% of the pooled population. Table 1 shows common adverse reactions in adults, excluding hypoglycemia, associated with the use of liraglutide injection for the treatment of type 2 diabetes mellitus. These adverse reactions occurred more commonly on liraglutide than on placebo and occurred in at least 5% of patients treated with liraglutide. Overall, the type, and severity of adverse reactions in pediatric patients 10 years of age and older and above were comparable to that observed in the adult population. Table 1. Adverse Reactions Reported in \u22655% of Adult Patients Treated with Liraglutide Injection for Type 2 Diabetes Mellitus Placebo N=661 Liraglutide 1.2 mg N= 645 Liraglutide 1.8 mg N= 1,024 Adverse Reaction (%) (%) (%) Nausea 5 18 20 Diarrhea 4 10 12 Headache 7 11 10 Nasopharyngitis 8 9 10 Vomiting 2 6 9 Decreased appetite 1 10 9 Dyspepsia 1 4 7 Upper Respiratory Tract Infection 6 7 6 Constipation 1 5 5 Back Pain 3 4 5 Cumulative proportions were calculated combining studies using Cochran-Mantel-Haenszel weights. In an analysis of placebo- and active-controlled trials, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 1 . Other Adverse Reactions Gastrointestinal Adverse Reactions In the pool of 5 glycemic control, placebo-controlled adult clinical trials, withdrawals due to gastrointestinal adverse reactions, occurred in 4.3% of liraglutide-treated patients and 0.5% of placebo-treated patients. Severe gastrointestinal adverse reactions were reported more frequently among patients receiving liraglutide (1.2 mg 4.4 %, 1.8 mg 4.2 %) than placebo (1.1 %). Withdrawal due to gastrointestinal adverse events mainly occurred during the first 2 to 3 months of the trials. Injection site reactions Injection site reactions (e.g., injection site rash, erythema) were reported in approximately 2% of liraglutide-treated adult patients in the five double-blind, glycemic control trials of at least 26 weeks duration. Less than 0.2% of liraglutide-treated patients discontinued due to injection site reactions. Hypoglycemia In 5 adult glycemic control, placebo-controlled clinical trials of at least 26 weeks duration, hypoglycemia requiring the assistance of another person for treatment occurred in 8 liraglutide-treated patients (7.5 events per 1,000 patient-years). Of these 8 liraglutide-treated patients, 7 patients were concomitantly using a sulfonylurea. Table 2. Adult Incidence (%) and Rate (episodes/patient year) of Hypoglycemia in 26-week Combination Therapy Placebo-controlled Trials Placebo Comparator Liraglutide Treatment Add-on to Metformin Placebo + Metformin (N = 121) Liraglutide + Metformin (N = 724) Patient not able to self-treat 0 0.1 (0.001) Patient able to self-treat 2.5 (0.06) 3.6 (0.05) Add-on to Glimepiride Placebo + Glimepiride (N = 114) Liraglutide + Glimepiride (N = 695) Patient not able to self-treat 0 0.1 (0.003) Patient able to self-treat 2.6 (0.17) 7.5 (0.38) Not classified 0 0.9 (0.05) Add-on to Metformin + Rosiglitazone Placebo + Metformin + Rosiglitazone (N = 175) Liraglutide + Metformin + Rosiglitazone (N = 355) Patient not able to self-treat 0 0 Patient able to self-treat 4.6 (0.15) 7.9 (0.49) Not classified 1.1 (0.03) 0.6 (0.01) Add-on to Metformin + Glimepiride Placebo + Metformin + Glimepiride (N = 114) Liraglutide + Metformin + Glimepiride (N = 230) Patient not able to self-treat 0 2.2 (0.06) Patient able to self-treat 16.7 (0.95) 27.4 (1.16) Not classified 0 0 \u201cPatient not able to self-treat\u201d is defined as an event requiring the assistance of another person for treatment. In a 26-week placebo-controlled clinical trial in pediatric patients 10 years of age and older with a 26-week open-label extension, 21.2% of liraglutide-treated patients (mean age 14.6 years) with type 2 diabetes mellitus, had hypoglycemia with a blood glucose <54 mg/dL with or without symptoms (335 events per 1,000 patient years). No severe hypoglycemic episodes occurred in the liraglutide treatment group (severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions). Papillary thyroid carcinoma In adult glycemic control trials of liraglutide injection, there were 7 reported cases of papillary thyroid carcinoma in patients treated with liraglutide and 1 case in a comparator-treated patient (1.5 vs. 0.5 cases per 1,000 patient-years). Most of these papillary thyroid carcinomas were <1 cm in greatest diameter and were diagnosed in surgical pathology specimens after thyroidectomy prompted by findings on protocol-specified screening with serum calcitonin or thyroid ultrasound. Pancreatitis In glycemic control trials of liraglutide injection, there have been 13 cases of pancreatitis among liraglutide-treated patients and 1 case in a comparator (glimepiride) treated patient (2.7 vs. 0.5 cases per 1,000 patient-years). Nine of the 13 cases with liraglutide were reported as acute pancreatitis and four were reported as chronic pancreatitis. In one case in a liraglutide-treated patient, pancreatitis, with necrosis, was observed and led to death; however clinical causality could not be established. Some patients had other risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse. Cholelithiasis and cholecystitis In adult glycemic control trials of liraglutide injection, the incidence of cholelithiasis was 0.3% in both liraglutide-treated and placebo-treated patients. The incidence of cholecystitis was 0.2% in both liraglutide-treated and placebo-treated patients. Laboratory Tests Bilirubin In the five adult glycemic control trials of at least 26 weeks duration, mildly elevated serum bilirubin concentrations (elevations to no more than twice the upper limit of the reference range) occurred in 4% of liraglutide-treated patients, 2.1% of placebo-treated patients and 3.5% of active-comparator-treated patients. This finding was not accompanied by abnormalities in other liver tests. The significance of this isolated finding is unknown. Calcitonin Calcitonin, a biological marker of MTC, was measured throughout the clinical development program. At the end of the adult glycemic control trials, adjusted mean serum calcitonin concentrations were higher in liraglutide-treated patients compared to placebo-treated patients but not compared to patients receiving active comparator. Between group differences in adjusted mean serum calcitonin values were approximately 0.1 ng/L or less. Among adult patients with pretreatment calcitonin <20 ng/L, calcitonin elevations to >20 ng/L occurred in 0.7% of liraglutide-treated patients, 0.3% of placebo-treated patients, and 0.5% of active-comparator-treated patients. The clinical significance of these findings is unknown. Lipase and Amylase In one adult glycemic control trial in renal impairment patients, a mean increase of 33% for lipase and 15% for amylase from baseline was observed for liraglutide-treated patients while placebo-treated patients had a mean decrease in lipase of 3% and a mean increase in amylase of 1%. The clinical significance of elevations in lipase or amylase with liraglutide is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions ( 5.2 )]. Vital signs Liraglutide injection did not have adverse effects on blood pressure. Mean increases from baseline in heart rate of 2 to 3 beats per minute have been observed in adult patients treated with liraglutide compared to placebo. 6.2 Postmarketing Experience The following additional adverse reactions have been reported during post-approval use of liraglutide injection. 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. Gastrointestinal: Acute pancreatitis; hemorrhagic and necrotizing pancreatitis sometimes resulting in death; ileus, intestinal obstruction, severe constipation including fecal impaction, nausea, vomiting and diarrhea leading to dehydration Hepatobiliary: Elevations of liver enzymes, hyperbilirubinemia, cholestasis, cholecystitis, cholelithiasis requiring cholecystectomy, hepatitis Hypersensitivity: Angioedema, anaphylactic reactions, pruritus Neoplasms: Medullary thyroid carcinoma Neurologic: Dysgeusia, dizziness, 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: Acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis; and increased serum creatinine Skin and subcutaneous tissue: Cutaneous amyloidosis, alopecia", "confidence": 1.0, "source_class": 0, "source_metadata": {"type": "openfda_label", "set_id": "0efc3a89-211a-4496-baab-e8265e07de2b", "section": "adverse_reactions", "effective_date": "20260130", "brand_name": "Liraglutide"}, "timestamp": 1770186233}
