FDA label fd835392-e712-4caa-b669-7f25933b076d

WARNING: RISK OF THYROID C-CELL TUMORS • Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions (5.1) and Nonclinical Toxicology (13.1) ] . • BYDUREON 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 BYDUREON and inform them of symptoms of thyroid tumors (e.g., mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with BYDUREON [see Contraindications (4) and Warnings and Precautions (5.1) ]. WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. • Exenatide extended-release causes thyroid C-cell tumors at clinically relevant exposures in rats. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC) in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined ( 5.1 , 13.1 ). • BYDUREON 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 ).

5 WARNINGS AND PRECAUTIONS • Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including BYDUREON. Discontinue if pancreatitis is suspected. ( 5.2 ) • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin: Patients taking an insulin secretagogue or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Reduction in the dose of insulin secretagogue or insulin may be necessary. ( 5.3 ) • Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.4 ) • Severe Gastrointestinal Adverse Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. BYDUREON is not recommended in patients with severe gastroparesis. ( 5.5 ) • Immunogenicity: Patients may develop antibodies to exenatide. If there is worsening glycemic control or failure to achieve target glycemic control, consider alternative antidiabetic therapy. ( 5.6 ) • Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported. In such cases, patients are to discontinue BYDUREON and promptly seek medical advice. ( 5.7 ) • Drug-induced Immune-mediated Thrombocytopenia: Serious bleeding which may be fatal has been reported. Discontinue BYDUREON promptly and avoid re-exposure to exenatide. ( 5.8 ) • Injection-site Reactions: Serious injection-site reactions with or without subcutaneous nodules have been reported. ( 5.9 ) • Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. ( 5.10 ) • Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. ( 5.11 ) 5.1 Risk of Thyroid C-cell Tumors In both genders of rats, exenatide extended-release caused a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures compared to controls [see Nonclinical Toxicology (13.1) ] . A statistically significant increase in malignant thyroid C-cell carcinomas was observed in female rats receiving exenatide extended-release at 25-times clinical exposure compared to controls and higher incidences were noted in males above controls in all treated groups at ≥2-times clinical exposure. The potential of exenatide extended-release to induce C-cell tumors in mice has not been evaluated. Other glucagon-like peptide-1 (GLP-1) receptor agonists have also induced thyroid C-cell adenomas and carcinomas in male and female mice and rats at clinically relevant exposures. It is unknown whether BYDUREON will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. BYDUREON is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk of MTC with the use of BYDUREON 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 BYDUREON. Such monitoring may increase the risk of unnecessary procedures, due to the low specificity of serum calcitonin testing for MTC and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC and patients with MTC usually have values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated. 5.2 Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including BYDUREON [see Adverse Reactions (6.2) ] . After initiation of BYDUREON, 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 BYDUREON and initiate appropriate management. 5.3 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving BYDUREON in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia [see Adverse Reactions (6.1) and Drug Interactions (7) ] . The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. 5.4 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, including BYDUREON [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 BYDUREON that could lead to volume depletion, especially when initiating BYDUREON. BYDUREON is not recommended for use in patients with an eGFR below 45 mL/min/1.73 m2 [see Use in Specific Populations (8.6)] . 5.5 Severe Gastrointestinal Adverse Reactions Use of GLP-1 receptor agonists, including BYDUREON, has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions (6) ] . BYDUREON is not recommended in patients with severe gastroparesis. 5.6 Immunogenicity In the 24- to 30-week treatment periods in Trials 1, 2, 3, 4 and 9 in adult patients with type 2 diabetes mellitus [see Clinical Studies (14.2 , 14.3 ) and Adverse Reactions (6.1) ] , BYDUREON-treated patients who had high titer anti-exenatide antibodies (defined as ≥625) had a lower glycemic response compared to BYDUREON-treated patients who did not have anti-exenatide antibodies [see Clinical Pharmacology (12.6)] . In the 24-week treatment period in Trial 8 in pediatric patients with type 2 diabetes mellitus [see Clinical Studies (14.5)] , BYDUREON-treated patients who had high titer anti-exenatide antibodies (≥625) appeared to have had a lower glycemic response compared to BYDUREON-treated patients who did not have anti exenatide antibodies. At Week 24, the mean change in HbA 1c from baseline in BYDUREON-treated patients was greater (-0.73%) in those with low titer anti-exenatide antibodies (<625) compared to +0.07% in those with high titer anti-exenatide antibodies [see Clinical Pharmacology (12.6)] . If there is worsening glycemic control or failure to achieve targeted glycemic control, consider stopping BYDUREON and using alternative antidiabetic therapy. 5.7 Hypersensitivity There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) in patients treated with exenatide. If a hypersensitivity reaction occurs, the patient should discontinue BYDUREON and promptly seek medical advice [see Contraindications (4) and Adverse Reactions (6.3) ]. 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 BYDUREON. 5.8 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 BYDUREON immediately and do not re-expose the patient to exenatide. Upon discontinuation, thrombocytopenia can persist due to the prolonged exenatide exposure from BYDUREON (about 10 weeks) [see Adverse Reactions (6.3) ] . 5.9 Injection-Site Reactions There have been postmarketing reports of serious injection-site reactions (e.g., abscess, cellulitis, and necrosis), with or without subcutaneous nodules, with the use of BYDUREON. Isolated cases required surgical intervention [see Adverse Reactions (6.1) ]. 5.10 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 the EXSCEL trial [see Clinical Studies (14.2) ] , 1.9% of BYDUREON-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. 5.11 Pulmonary Aspiration During General Anesthesia or Deep Sedation BYDUREON 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 BYDUREON, including whether modifying preoperative fasting recommendations or temporarily discontinuing BYDUREON 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 BYDUREON.

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 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) ] • Injection-Site Reactions [see Warnings and Precautions (5.9) ] • Acute Gallbladder Disease [see Warnings and Precautions (5.10) ] • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions (5.11) ] Most common (≥5%) and occurring more frequently than comparator in clinical trials: nausea, diarrhea, headache, vomiting, constipation, injection-site pruritus, injection-site nodule, and dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. The safety data presented below are derived from six comparator-controlled trials of BYDUREON in adult patients who entered the studies not achieving adequate glycemic control on their current therapy [see Clinical Studies (14.1 )] . In a double-blind 26-week trial, patients on diet and exercise were treated with BYDUREON 2 mg once every 7 days (weekly), sitagliptin 100 mg daily, pioglitazone 45 mg daily, or metformin 2000 mg daily. In a double-blind 26-week trial, patients on metformin were treated with BYDUREON 2 mg once every 7 days (weekly), sitagliptin 100 mg daily, or pioglitazone 45 mg daily. In an open-label 26-week trial, patients on metformin or metformin plus sulfonylurea were treated with BYDUREON 2 mg once every 7 days (weekly) or optimized insulin glargine. In two open-label 24- to 30-week studies, patients on diet and exercise or metformin, a sulfonylurea, a thiazolidinedione, or combination of oral agents were treated with BYDUREON 2 mg once every 7 days (weekly) or BYETTA 10 mcg twice daily. In an open-label 26-week trial, patients on metformin, a sulfonylurea, metformin plus a sulfonylurea, or metformin plus pioglitazone were treated with BYDUREON 2 mg every 7 days (weekly) or liraglutide 1.8 mg once daily. The safety of BYDUREON in pediatric patients age 10 to less than 18 years with type 2 diabetes was similar to that observed in adults [see Clinical Studies (14.3) ] . Common Adverse Reactions Tables 1 and 2 summarize adverse reactions in adults with an incidence ≥5% reported in the six comparator-controlled 24- to 30-week trials of BYDUREON used as monotherapy or as add-on to metformin, a sulfonylurea, a thiazolidinedione, or combination of these oral antidiabetic agents. Table 1: Adverse Reactions Reported in ≥5% of BYDUREON-Treated Patients with Type 2 Diabetes Mellitus in Monotherapy Trial 26-Week Monotherapy Trial BYDUREON 2 mg N = 248 % Sitagliptin 100 mg N = 163 % Pioglitazone 30-45 (mean dose 40) mg N = 163 % Metformin 1000-2500 (mean dose 2077) mg N = 246 % Nausea 11.3 3.7 4.3 6.9 Diarrhea 10.9 5.5 3.7 12.6 Injection-site nodule Patients in the sitagliptin, pioglitazone, and metformin treatment groups received weekly placebo injections. 10.5 6.7 3.7 10.2 Constipation 8.5 2.5 1.8 3.3 Headache 8.1 9.2 8.0 12.2 Dyspepsia 7.3 1.8 4.9 3.3 N = number of intent-to-treat patients. Note: Percentages are based on the number of intent-to-treat patients in each treatment group. Table 2: Adverse Reactions Reported in ≥5% of BYDUREON-Treated Patients with Type 2 Diabetes Mellitus in 24- to 30-Week Add-On Combination Therapy Trials 26-Week Add-On to Metformin Trial BYDUREON 2 mg N = 160 % Sitagliptin 100 mg N = 166 % Pioglitazone 45 mg N = 165 % Nausea 24.4 9.6 4.8 Diarrhea 20.0 9.6 7.3 Vomiting 11.3 2.4 3.0 Headache 9.4 9.0 5.5 Constipation 6.3 3.6 1.2 Fatigue 5.6 0.6 3.0 Dyspepsia 5.0 3.6 2.4 Decreased appetite 5.0 1.2 0.0 Injection-site pruritus Patients in the sitagliptin, pioglitazone, and metformin treatment groups received weekly placebo injections. 5.0 4.8 1.2 26-Week Add-On to Metformin or Metformin + Sulfonylurea Trial BYDUREON 2 mg N = 233 % Insulin Glargine Titrated N = 223 % Nausea 12.9 1.3 Headache 9.9 7.6 Diarrhea 9.4 4.0 Injection-site nodule 6.0 0.0 30-Week Monotherapy or as Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial BYDUREON 2 mg N = 148 % BYETTA 10 mcg N = 145 % Nausea 27.0 33.8 Diarrhea 16.2 12.4 Vomiting 10.8 18.6 Injection-site pruritus 18.2 1.4 Constipation 10.1 6.2 Gastroenteritis viral 8.8 5.5 Gastroesophageal reflux disease 7.4 4.1 Dyspepsia 7.4 2.1 Injection-site erythema 7.4 0.0 Fatigue 6.1 3.4 Headache 6.1 4.8 Injection-site hematoma 5.4 11.0 24-Week Monotherapy or as Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial BYDUREON 2 mg N = 129 % BYETTA 10 mcg N = 123 % Nausea 14.0 35.0 Diarrhea 9.3 4.1 Injection-site erythema 5.4 2.4 26-Week Add-On to Metformin, a Sulfonylurea, Metformin + Sulfonylurea, or Metformin + Pioglitazone Trial BYDUREON 2 mg N = 461 % Injection-site nodule 10.4 Nausea 9.3 Diarrhea 6.1 N = number of intent-to-treat patients. Note: Percentages are based on the number of intent-to-treat patients in each treatment group. Nausea was a common adverse reaction associated with initiation of treatment with BYDUREON and usually decreased over time. Adverse Reactions Leading to Study Withdrawal The incidence of withdrawal due to adverse reactions in adults was 4.1% (N=57) for BYDUREON-treated patients, 4.9% (N=13) for BYETTA-treated patients, and 2.9% (N=46) for other comparator-treated patients in the six comparator-controlled 24- to 30-week trials. The most common classes of adverse reactions (0.5%) leading to withdrawal for BYDUREON-treated patients were, Gastrointestinal Disorders 1.6% (N=22) versus 4.1% (N=11) for BYETTA and 1.9% (N=30) for other comparators, and Administration Site Conditions 0.8% (N=11) versus 0.0% for BYETTA and 0.2% (N=3) for other comparators. The most frequent adverse reactions within each of these respective classes were, nausea 0.4% (N=6) for BYDUREON versus 1.5% (N=4) for BYETTA and 0.8% (N=12) for other comparators, and injection-site nodule, 0.4% (N=6) for BYDUREON versus 0.0% for BYETTA and 0.0% for other comparators. Hypoglycemia Table 3 summarizes the incidence of hypoglycemia (defined as the presence of symptoms of hypoglycemia with a concomitant glucose <54 mg/dL and the ability to self-treat) in the six comparator-controlled 24- to 30-week trials in adults of BYDUREON used as monotherapy or as add-on to metformin, a sulfonylurea, a thiazolidinedione, or combination of these oral antidiabetic agents. Table 3: Incidence (% of Subjects) of Hypoglycemia Reported event that has symptoms consistent with hypoglycemia with a concomitant glucose <54 mg/dL and the patient was able to self-treat. in Clinical Trials in Patients with Type 2 Diabetes Mellitus 26-Week Monotherapy Trial BYDUREON 2 mg (N = 248) 2.0% Sitagliptin 100 mg (N = 163) 0.0% Pioglitazone 30-45 (mean dose 40) mg (N = 163) 0.0% Metformin 1000-2500 (mean dose 2077) mg (N = 246) 0.0% 26-Week Add-On to Metformin Trial BYDUREON 2 mg (N = 160) 1.3% Sitagliptin 100 mg (N = 166) 3.0% Pioglitazone 45 mg (N = 165) 1.2% 26-Week Add-On to Metformin or Metformin + Sulfonylurea Trial With Concomitant Sulfonylurea Use (N = 136) BYDUREON 2 mg (N = 70) 20.0% Titrated Insulin Glargine (N = 66) 43.9% Without Concomitant Sulfonylurea Use (N = 320) BYDUREON 2 mg (N = 163) 3.7% Titrated Insulin Glargine Insulin glargine was dosed to a target fasting glucose concentration of 72 to 100 mg/dL. The mean dose of insulin glargine was 10 units/day at baseline and 31 units/day at endpoint. (N = 157) 19.1% 24-Week Monotherapy or Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial With Concomitant Sulfonylurea Use (N = 74) BYDUREON 2 mg (N = 40) 12.5% BYETTA 10 mcg (N = 34) 11.8% Without Concomitant Sulfonylurea Use (N = 178) BYDUREON 2 mg (N = 89) 0.0% BYETTA 10 mcg (N = 89) 0.0% 30-Week Monotherapy or Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial With Concomitant Sulfonylurea Use (N = 107) BYDUREON 2 mg (N = 55) 14.5% BYETTA 10 mcg (N = 52) 15.4% Without Concomitant Sulfonylurea Use (N = 186) BYDUREON 2 mg (N = 93) 0.0% BYETTA 10 mcg (N = 93) 1.1% 26-Week as Add-On to Metformin, a Sulfonylurea, Metformin + Sulfonylurea, or Metformin + Pioglitazone Trial With Concomitant Sulfonylurea Use (N = 590) BYDUREON 2 mg (N = 294) 15.3% Without Concomitant Sulfonylurea Use (N = 321) BYDUREON 2 mg (N = 167) 3.6% N = number of intent-to-treat (ITT) patients. Note: Percentages are based on the number of ITT patients in each treatment group. In the 24-week pediatric placebo-controlled clinical trial (Trial 8) [see Clinical Studies (14.5)] , 2 (3.4%) of BYDUREON-treated patients with type 2 diabetes had hypoglycemia with a blood glucose <54 mg/dL with or without symptoms and 1 (1.7%) had severe hypoglycemia (defined as an episode with severe cognitive impairment requiring external assistance for recovery). Injection-Site Adverse Reactions Including Nodules In five comparator-controlled 24- to 30-week trials in adults, injection-site reactions were observed more frequently in BYDUREON-treated patients (17%) than in BYETTA-treated patients (13%), titrated insulin glargine-treated patients (1.8%), or placebo-treated patients (sitagliptin (11%), pioglitazone (6%), and metformin (13%) treatment groups). One percent of BYDUREON-treated patients withdrew due to injection-site adverse reactions (injection-site mass, injection-site nodule, injection-site pruritus, and injection-site reaction). In a separate 15-week study of BYDUREON in adults in which information on nodules were collected and analyzed, 24 out of 31 subjects (77%) experienced at least 1 injection-site nodule during treatment; 2 subjects (7%) reported accompanying localized symptoms. The mean duration of events was 27 days. Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions Injection site reactions for BYDUREON-treated patients were more commonly observed in those who were antibody-positive (anti-exenatide antibodies) (14%) compared with those who were antibody-negative (3%) [see Clinical Pharmacology (12.6)]. Increase in Heart Rate Increases in heart rate from baseline ranging from 1.5 to 4.5 beats per minute have been observed in BYDUREON-treated patients in comparator-controlled clinical trials in adults. Cholelithiasis and cholecystitis In the EXSCEL trial [see Clinical Studies (14.4)] , 1.9% of BYDUREON-treated patients and 1.4% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. Other Adverse Reactions The following adverse reactions were also reported in three 30-week controlled trials (in adults with type 2 diabetes mellitus) of BYETTA (N=963) add-on to metformin and/or sulfonylurea, with an incidence of ≥1% and reported more frequently than with placebo: feeling jittery (9% BYETTA, 4% placebo), dizziness (9% BYETTA, 6% placebo), asthenia (4% BYETTA, 2% placebo), and hyperhidrosis (3% BYETTA, 1% placebo). 6.2 Postmarketing Experience The following additional adverse reactions have been reported during post-approval use of BYDUREON 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 : Increased international normalized ratio (INR), sometimes associated with bleeding, with concomitant warfarin use [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 (e.g., abscess, cellulitis, and necrosis, with or without subcutaneous nodules), 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 Disorders : Alopecia.

<table width="100%"><col width="20%"/><col width="20%"/><col width="20%"/><col width="20%"/><col width="20%"/><tbody><tr><td align="center" colspan="5" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">26-Week Monotherapy Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">BYDUREON</content></paragraph><paragraph><content styleCode="bold">2 mg</content></paragraph><paragraph><content styleCode="bold">N = 248</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Sitagliptin</content></paragraph><paragraph><content styleCode="bold">100 mg</content></paragraph><paragraph><content styleCode="bold">N = 163</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Pioglitazone</content></paragraph><paragraph><content styleCode="bold">30-45 (mean dose</content></paragraph><paragraph><content styleCode="bold">40) mg</content></paragraph><paragraph><content styleCode="bold">N = 163</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Metformin</content></paragraph><paragraph><content styleCode="bold">1000-2500 (mean dose 2077) mg</content></paragraph><paragraph><content styleCode="bold">N = 246</content></paragraph><paragraph><content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6.9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10.9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>5.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site nodule<footnote ID="_Ref108164960">Patients in the sitagliptin, pioglitazone, and metformin treatment groups received weekly placebo injections.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.7</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.5</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8.1</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>9.2</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8.0</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dyspepsia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>7.3</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.8</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4.9</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.3</paragraph></td></tr><tr><td colspan="5" styleCode="Toprule " valign="top"><paragraph>N = number of intent-to-treat patients.</paragraph><paragraph>Note: Percentages are based on the number of intent-to-treat patients in each treatment group.</paragraph></td></tr></tbody></table>

<table width="100%"><col width="41%"/><col width="21%"/><col width="18%"/><col width="20%"/><tbody><tr><td align="center" colspan="4" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">26-Week Add-On to Metformin Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">BYDUREON</content> <content styleCode="bold">2 mg</content> <content styleCode="bold">N = 160</content> <content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Sitagliptin</content> <content styleCode="bold">100 mg</content> <content styleCode="bold">N = 166</content> <content styleCode="bold">%</content></paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Pioglitazone</content> <content styleCode="bold">45 mg</content> <content styleCode="bold">N = 165</content> <content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>24.4</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>9.6</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>4.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20.0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9.6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vomiting</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11.3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2.4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9.4</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9.0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6.3</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dyspepsia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.6</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.2</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site pruritus<footnote ID="_Ref108165041">Patients in the sitagliptin, pioglitazone, and metformin treatment groups received weekly placebo injections.</footnote></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.0</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4.8</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.2</paragraph></td></tr><tr><td align="center" colspan="4" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">26-Week Add-On to Metformin or Metformin + Sulfonylurea Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">BYDUREON</content> <content styleCode="bold">2 mg</content> <content styleCode="bold">N = 233</content> <content styleCode="bold">%</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">Insulin Glargine Titrated</content> <content styleCode="bold">N = 223</content> <content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12.9</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>1.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9.9</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>7.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9.4</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>4.0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site nodule</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6.0</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>0.0</paragraph></td></tr><tr><td align="center" colspan="4" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">30-Week Monotherapy or as Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">BYDUREON</content> <content styleCode="bold">2 mg</content> <content styleCode="bold">N = 148</content> <content styleCode="bold">%</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">BYETTA</content> <content styleCode="bold">10 mcg</content> <content styleCode="bold">N = 145</content> <content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>27.0</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>33.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16.2</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>12.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vomiting</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10.8</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>18.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site pruritus</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18.2</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>1.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10.1</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>6.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Gastroenteritis viral</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8.8</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>5.5</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Gastroesophageal reflux disease</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7.4</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>4.1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dyspepsia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7.4</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>2.1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site erythema</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7.4</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>0.0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6.1</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>3.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6.1</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>4.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site hematoma</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.4</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>11.0</paragraph></td></tr><tr><td align="center" colspan="4" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">24-Week Monotherapy or as Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">BYDUREON</content> <content styleCode="bold">2 mg</content> <content styleCode="bold">N = 129</content> <content styleCode="bold">%</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">BYETTA</content> <content styleCode="bold">10 mcg</content> <content styleCode="bold">N = 123</content> <content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14.0</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>35.0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9.3</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>4.1</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site erythema</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.4</paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule " valign="top"><paragraph>2.4</paragraph></td></tr><tr><td align="center" colspan="4" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">26-Week Add-On to Metformin, a Sulfonylurea, Metformin + Sulfonylurea, or Metformin + Pioglitazone Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"><paragraph><content styleCode="bold">BYDUREON</content> <content styleCode="bold">2 mg</content> <content styleCode="bold">N = 461</content> <content styleCode="bold">%</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection-site nodule</paragraph></td><td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"><paragraph>10.4</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"><paragraph>9.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" colspan="3" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>6.1</paragraph></td></tr><tr><td colspan="4" styleCode="Toprule " valign="top"><paragraph>N = number of intent-to-treat patients. Note: Percentages are based on the number of intent-to-treat patients in each treatment group.</paragraph></td></tr></tbody></table>

<table width="100%"><caption>Table 3: Incidence (% of Subjects) of Hypoglycemia<footnote ID="_Ref108165103">Reported event that has symptoms consistent with hypoglycemia with a concomitant glucose &lt;54 mg/dL and the patient was able to self-treat.</footnote> in Clinical Trials in Patients with Type 2 Diabetes Mellitus</caption><col width="85%"/><col width="15%"/><tbody><tr><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">26-Week Monotherapy Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 248)</paragraph></td><td align="center" styleCode="Rrule Toprule Botrule " valign="top"><paragraph>2.0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sitagliptin 100 mg (N = 163)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pioglitazone 30-45 (mean dose 40) mg (N = 163)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Metformin 1000-2500 (mean dose 2077) mg (N = 246)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.0%</paragraph></td></tr><tr><td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">26-Week Add-On to Metformin Trial</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 160)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.3%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sitagliptin 100 mg (N = 166)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pioglitazone 45 mg (N = 165)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.2%</paragraph></td></tr><tr><td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">26-Week Add-On to Metformin or Metformin + Sulfonylurea Trial</content></paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">With Concomitant Sulfonylurea Use (N = 136)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 70)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20.0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Titrated Insulin Glargine (N = 66)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>43.9%</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Without Concomitant Sulfonylurea Use (N = 320)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 163)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3.7%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Titrated Insulin Glargine<footnote ID="_Ref108165167">Insulin glargine was dosed to a target fasting glucose concentration of 72 to 100 mg/dL. The mean dose of insulin glargine was 10 units/day at baseline and 31 units/day at endpoint.</footnote> (N = 157)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19.1%</paragraph></td></tr><tr><td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">24-Week Monotherapy or Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial</content></paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">With Concomitant Sulfonylurea Use (N = 74)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 40)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12.5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYETTA 10 mcg (N = 34)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11.8%</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Without Concomitant Sulfonylurea Use (N = 178)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 89)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYETTA 10 mcg (N = 89)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.0%</paragraph></td></tr><tr><td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">30-Week Monotherapy or Add-On to Metformin, a Sulfonylurea, a Thiazolidinedione, or Combination of Oral Agents Trial</content></paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">With Concomitant Sulfonylurea Use (N = 107)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 55)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14.5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYETTA 10 mcg (N = 52)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15.4%</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Without Concomitant Sulfonylurea Use (N = 186)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 93)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0.0%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYETTA 10 mcg (N = 93)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1.1%</paragraph></td></tr><tr><td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">26-Week as Add-On to Metformin, a Sulfonylurea, Metformin + Sulfonylurea, or Metformin + Pioglitazone Trial</content></paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">With Concomitant Sulfonylurea Use (N = 590)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 294)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15.3%</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Lrule " valign="top"><paragraph><content styleCode="bold">Without Concomitant Sulfonylurea Use (N = 321)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>BYDUREON 2 mg (N = 167)</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.6%</paragraph></td></tr><tr><td colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>N = number of intent-to-treat (ITT) patients. Note: Percentages are based on the number of ITT patients in each treatment group.</paragraph></td></tr></tbody></table>