FDA label e0cceca4-759d-4ca9-be65-23a0199e5766

5 WARNINGS AND PRECAUTIONS Pancreatitis: Postmarketing reports with exenatide, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. Discontinue BYETTA promptly. BYETTA should not be restarted. Consider other antidiabetic therapies in patients with a history of pancreatitis ( 5.1 ). Hypoglycemia: Increased risk when BYETTA is used in combination with medications known to cause hypoglycemia (e.g. insulin or insulin secretagogue). Consider reducing the dose of insulin or insulin secretagogue ( 5.2 ). Renal Impairment: Postmarketing reports with exenatide, sometimes requiring hemodialysis and kidney transplantation. BYETTA should not be used in patients with severe renal impairment or end-stage renal disease and should be used with caution in patients with renal transplantation. Caution should be applied when initiating BYETTA or escalating the dose of BYETTA in patients with moderate renal failure ( 5.3 , 8.6 , 12.3 ) Severe Gastrointestinal Disease: Use of BYETTA is not recommended in patients with severe gastrointestinal disease (e.g., gastroparesis) ( 5.4 ). Hypersensitivity: Postmarketing reports with exenatide of hypersensitivity reactions (e.g. anaphylaxis and angioedema). The patient should discontinue BYETTA and other suspect medications and promptly seek medical advice ( 5.6 ). Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with BYETTA or any other antidiabetic drug ( 5.7 ). 5.1 Acute Pancreatitis Based on postmarketing data BYETTA has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation of BYETTA, and after dose increases, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting). If pancreatitis is suspected, BYETTA should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, BYETTA should not be restarted. Consider antidiabetic therapies other than BYETTA in patients with a history of pancreatitis. 5.2 Use with Medications Known to Cause Hypoglycemia The risk of hypoglycemia is increased when BYETTA is used in combination with a sulfonylurea. Therefore, patients receiving BYETTA and a sulfonylurea may require a lower dose of the sulfonylurea to reduce the risk of hypoglycemia. When BYETTA is used in combination with insulin, the dose of insulin should be evaluated. In patients at increased risk of hypoglycemia consider reducing the dose of insulin [s ee Adverse Reactions (6.1) ] . The concurrent use of BYETTA with prandial insulin has not been studied and cannot be recommended. It is also possible that the use of BYETTA with other glucose-independent insulin secretagogues (e.g. meglitinides) could increase the risk of hypoglycemia. For additional information on glucose dependent effects see Mechanism of Action (12.1) . 5.3 Renal Impairment BYETTA should not be used in patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease and should be used with caution in patients with renal transplantation [see Use in Specific Populations (8.6) ] . In patients with end-stage renal disease receiving dialysis, single doses of BYETTA 5 mcg were not well-tolerated due to gastrointestinal side effects. Because BYETTA may induce nausea and vomiting with transient hypovolemia, treatment may worsen renal function. Caution should be applied when initiating or escalating doses of BYETTA from 5 mcg to 10 mcg in patients with moderate renal impairment (creatinine clearance 30 to 50 mL/min). There have been postmarketing reports of altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure and acute renal failure, sometimes requiring hemodialysis or kidney transplantation. Some of these events occurred in patients receiving one or more pharmacologic agents known to affect renal function or hydration status, such as angiotensin converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, or diuretics. Some events occurred in patients who had been experiencing nausea, vomiting, or diarrhea, with or without dehydration. Reversibility of altered renal function has been observed in many cases with supportive treatment and discontinuation of potentially causative agents, including BYETTA. Exenatide has not been found to be directly nephrotoxic in preclinical or clinical studies. 5.4 Gastrointestinal Disease BYETTA has not been studied in patients with severe gastrointestinal disease, including gastroparesis. Because BYETTA is commonly associated with gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea, the use of BYETTA is not recommended in patients with severe gastrointestinal disease. 5.5 Immunogenicity Patients may develop antibodies to exenatide following treatment with BYETTA. Antibody levels were measured in 90% of subjects in the 30-week, 24-week and 16-week studies of BYETTA. In 3%, 4% and 1% of these patients, respectively, antibody formation was associated with an attenuated glycemic response. If there is worsening glycemic control or failure to achieve targeted glycemic control, alternative antidiabetic therapy should be considered [see Adverse Reactions (6.1) ] . 5.6 Hypersensitivity There have been postmarketing reports of serious hypersensitivity reactions (e.g. anaphylaxis and angioedema) in patients treated with BYETTA. If a hypersensitivity reaction occurs, the patient should discontinue BYETTA and other suspect medications and promptly seek medical advice [see Adverse Reactions (6.2) ] . 5.7 Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with BYETTA or any other antidiabetic drug.

6 ADVERSE REACTIONS Most common (≥5%) and occurring more frequently than placebo in clinical trials: nausea, hypoglycemia, vomiting, diarrhea, feeling jittery, dizziness, headache, dyspepsia, constipation, asthenia. Nausea usually decreases over time ( 5.2 , 6 ). Postmarketing reports with exenatide of increased international normalized ratio (INR) with concomitant use of warfarin, sometimes with bleeding ( 6.2 , 7.2 ). To report SUSPECTED ADVERSE REACTIONS contact Amylin Pharmaceuticals, Inc. at 1-800-868-1190 and www.byetta.com 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. Hypoglycemia Table 1 summarizes the incidence and rate of hypoglycemia with BYETTA in six placebo-controlled clinical trials. Table 1: Incidence (%) and Rate of Hypoglycemia When BYETTA was Used as Monotherapy or With Concomitant Antidiabetic Therapy in Six Placebo-Controlled Clinical Trials A hypoglycemic episode was recorded if a patient reported symptoms of hypoglycemia with or without a blood glucose value consistent with hypoglycemia. Severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose value consistent with hypoglycemia or prompt recovery after treatment for hypoglycemia. BYETTA Placebo twice daily 5 mcg twice daily 10 mcg twice daily N = The number of Intent-to-Treat subjects in each treatment group. Monotherapy (24 Weeks) N 77 77 78 % Overall 1.3% 5.2% 3.8% Rate (episodes/patient-year) 0.03 0.21 0.52 % Severe 0.0% 0.0% 0.0% With Metformin (30 Weeks) N 113 110 113 % Overall 5.3% 4.5% 5.3% Rate (episodes/patient-year) 0.12 0.13 0.12 % Severe 0.0% 0.0% 0.0% With a Sulfonylurea (30 Weeks) N 123 125 129 % Overall 3.3% 14.4% 35.7% Rate (episodes/patient-year) 0.07 0.64 1.61 % Severe 0.0% 0.0% 0.0% With Metformin and a Sulfonylurea (30 Weeks) N 247 245 241 % Overall 12.6% 19.2% 27.8% Rate (episodes/patient-year) 0.58 0.78 1.71 % Severe 0.0% 0.4% 0.0% With a Thiazolidinedione (16 Weeks) N 112 not evaluated 121 % Overall 7.1% not evaluated 10.7% Rate (episodes/patient-years) 0.56 not evaluated 0.98 % Severe 0.0% not evaluated 0.0% With Insulin Glargine (30 Weeks) When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA 1c ≤ 8.0 % to minimize the risk of hypoglycemia. See Table 9 for insulin dose titration algorithm. N 122 not evaluated 137 % Overall 29.5% not evaluated 24.8% Rate (episodes/patient-years) 1.58 not evaluated 1.61 % Severe 0.8% not evaluated 0.0% Immunogenicity Antibodies were assessed in 90% of subjects in the 30-week, 24-week and 16-week studies of BYETTA. In the 30-week controlled trials of BYETTA add-on to metformin and/or sulfonylurea, antibodies were assessed at 2- to 6-week intervals. The mean antibody titer peaked at week 6 and was reduced by 55% by week 30. Three hundred and sixty patients (38%) had low titer antibodies (<625) to exenatide at 30 weeks. The level of glycemic control (HbA 1c ) in these patients was generally comparable to that observed in the 534 patients (56%) without antibody titers. An additional 59 patients (6%) had higher titer antibodies (≥625) at 30 weeks. Of these patients, 32 (3% overall) had an attenuated glycemic response to BYETTA; the remaining 27 (3% overall) had a glycemic response comparable to that of patients without antibodies [ see Warnings and Precautions (5.5) ]. In the 16-week trial of BYETTA add-on to thiazolidinediones, with or without metformin, 36 patients (31%) had low titer antibodies to exenatide at 16 weeks. The level of glycemic control in these patients was generally comparable to that observed in the 69 patients (60%) without antibody titer. An additional 10 patients (9%) had higher titer antibodies at 16 weeks. Of these patients, 4 (4% overall) had an attenuated glycemic response to BYETTA; the remaining 6 (5% overall) had a glycemic response comparable to that of patients without antibodies [ see Warnings and Precautions (5.5) ]. In the 24-week trial of BYETTA used as monotherapy, 40 patients (28%) had low titer antibodies to exenatide at 24 weeks. The level of glycemic control in these patients was generally comparable to that observed in the 101 patients (70%) without antibody titers. An additional 3 patients (2%) had higher titer antibodies at 24 weeks. Of these patients, 1 (1% overall) had an attenuated glycemic response to BYETTA; the remaining 2 (1% overall) had a glycemic response comparable to that of patients without antibodies [see Warnings and Precautions (5.5) ] . Antibodies to exenatide were not assessed in the 30-week trial of BYETTA used in combination with insulin glargine. Two hundred and ten patients with antibodies to exenatide in the BYETTA clinical trials were tested for the presence of cross-reactive antibodies to GLP-1 and/or glucagon. No treatment-emergent cross reactive antibodies were observed across the range of titers. Other Adverse Reactions Monotherapy For the 24-week placebo-controlled study of BYETTA used as a monotherapy, Table 2 summarizes adverse reactions (excluding hypoglycemia) occurring with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients. Table 2: Treatment-Emergent Adverse Reactions ≥2% Incidence With BYETTA Used as Monotherapy (Excluding Hypoglycemia) In a 24-week placebo-controlled trial. Monotherapy Placebo BID N = 77 % All BYETTA BID N = 155 % BID = twice daily. Nausea 0 8 Vomiting 0 4 Dyspepsia 0 3 Adverse reactions reported in ≥1.0 to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite, diarrhea, and dizziness. The most frequently reported adverse reaction associated with BYETTA, nausea, occurred in a dose-dependent fashion. Two of the 155 patients treated with BYETTA withdrew due to adverse reactions of headache and nausea. No placebo-treated patients withdrew due to adverse reactions. Combination Therapy Add-on to metformin and/or sulfonylurea In the three 30-week controlled trials of BYETTA add-on to metformin and/or sulfonylurea, adverse reactions (excluding hypoglycemia) with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients [see Warnings and Precautions (5.2) ] are summarized in Table 3. Table 3: Treatment-Emergent Adverse Reactions ≥2% Incidence and Greater Incidence With BYETTA Treatment Used With Metformin and/or a Sulfonylurea (Excluding Hypoglycemia) In three 30-week placebo-controlled clinical trials. Placebo BID N = 483 % All BYETTA BID N = 963 % BID = twice daily. Nausea 18 44 Vomiting 4 13 Diarrhea 6 13 Feeling Jittery 4 9 Dizziness 6 9 Headache 6 9 Dyspepsia 3 6 Asthenia 2 4 Gastroesophageal Reflux Disease 1 3 Hyperhidrosis 1 3 Adverse reactions reported in ≥1.0 to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite. Nausea was the most frequently reported adverse reaction and occurred in a dose-dependent fashion. With continued therapy, the frequency and severity decreased over time in most of the patients who initially experienced nausea. Patients in the long-term uncontrolled open-label extension studies at 52 weeks reported no new types of adverse reactions than those observed in the 30-week controlled trials. The most common adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (3% of patients) and vomiting (1%). For placebo-treated patients, <1% withdrew due to nausea and none due to vomiting. Add-on to thiazolidinedione with or without metformin For the 16-week placebo-controlled study of BYETTA add-on to a thiazolidinedione, with or without metformin, Table 4 summarizes the adverse reactions (excluding hypoglycemia) with an incidence of ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients. Table 4: Treatment-Emergent Adverse Reactions ≥2% Incidence With BYETTA Used With a Thiazolidinedione, With or Without Metformin (Excluding Hypoglycemia) In a 16-week placebo-controlled clinical trial. With a TZD or TZD/MET Placebo N = 112 % All BYETTA BID N = 121 % BID = twice daily. Nausea 15 40 Vomiting 1 13 Dyspepsia 1 7 Diarrhea 3 6 Gastroesophageal Reflux Disease 0 3 Adverse reactions reported in ≥1.0 to <2.0% of patients receiving BYETTA and reported more frequently than with placebo included decreased appetite. Chills (n = 4) and injection-site reactions (n = 2) occurred only in BYETTA-treated patients. The two patients who reported an injection-site reaction had high titers of antibodies to exenatide. Two serious adverse events (chest pain and chronic hypersensitivity pneumonitis) were reported in the BYETTA arm. No serious adverse events were reported in the placebo arm. The most common adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (9%) and vomiting (5%). For placebo-treated patients, <1% withdrew due to nausea. Add-on to insulin glargine with or without metformin and/or thiazolidinedione For the 30-week placebo-controlled study of BYETTA as add-on to insulin glargine with or without oral antihyperglycemic medications, Table 5 summarizes adverse reactions (excluding hypoglycemia) occurring with an incidence ≥2% and occurring more frequently in BYETTA-treated patients compared with placebo-treated patients. Table 5: Treatment-Emergent Adverse Reactions ≥2% Incidence With BYETTA Used With Insulin Glargine With or Without Oral Antihyperglycemic Medications (Excluding Hypoglycemia) In a 30-week placebo-controlled clinical trial. With Insulin Glargine Placebo N = 122 % All BYETTA BID N = 137 % BID = twice daily. Nausea 8 41 Vomiting 4 18 Diarrhea 8 18 Headache 4 14 Constipation 2 10 Dyspepsia 2 7 Asthenia 1 5 Abdominal Distension 1 4 Decreased Appetite 0 3 Flatulence 1 2 Gastroesophageal Reflux Disease 1 2 The most frequently reported adverse reactions leading to withdrawal for BYETTA-treated patients were nausea (5.1%) and vomiting (2.9%). No placebo-treated patients withdrew due to nausea or vomiting. 6.2 Post-Marketing Experience The following additional adverse reactions have been reported during post-approval use of BYETTA. 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. Allergy/Hypersensitivity: injection-site reactions, generalized pruritus and/or urticaria, macular or papular rash, angioedema, anaphylactic reaction [see Warnings and Precautions (5.6) ] . Drug Interactions: International normalized ratio (INR) increased with concomitant warfarin use sometimes associated with bleeding [see Drug Interactions (7.2) ] . Gastrointestinal: nausea, vomiting, and/or diarrhea resulting in dehydration; abdominal distension, abdominal pain, eructation, constipation, flatulence, acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death [see Limitations of Use (1.2) and Warnings and Precautions (5.1) ] . Neurologic: dysgeusia; somnolence Renal and Urinary Disorders: 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 [see Warnings and Precautions (5.3) ] . Skin and Subcutaneous Tissue Disorders: alopecia

<table width="100%" ID="table1"> <caption>Table 1: Incidence (%) and Rate of Hypoglycemia When BYETTA was Used as Monotherapy or With Concomitant Antidiabetic Therapy in Six Placebo-Controlled Clinical Trials<footnote>A hypoglycemic episode was recorded if a patient reported symptoms of hypoglycemia with or without a blood glucose value consistent with hypoglycemia. Severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose value consistent with hypoglycemia or prompt recovery after treatment for hypoglycemia.</footnote> </caption> <col width="25%" align="center" valign="top"/> <col width="25%" align="center" valign="top"/> <col width="25%" align="center" valign="top"/> <col width="25%" align="center" valign="top"/> <thead> <tr> <th styleCode="Lrule Rrule" rowspan="2"/> <th styleCode="Rrule Botrule" colspan="3">BYETTA</th> </tr> <tr> <th styleCode="Rrule">Placebo twice daily</th> <th styleCode="Rrule">5 mcg twice daily</th> <th styleCode="Rrule">10 mcg twice daily</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4">N = The number of Intent-to-Treat subjects in each treatment group.</td> </tr> </tfoot> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule" colspan="4" align="left"> <content styleCode="bold">Monotherapy (24 Weeks)</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">N</td> <td styleCode="Rrule">77</td> <td styleCode="Rrule">77</td> <td styleCode="Rrule">78</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Overall</td> <td styleCode="Rrule">1.3%</td> <td styleCode="Rrule">5.2%</td> <td styleCode="Rrule">3.8%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Rate (episodes/patient-year)</td> <td styleCode="Rrule">0.03</td> <td styleCode="Rrule">0.21</td> <td styleCode="Rrule">0.52</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Severe</td> <td styleCode="Rrule">0.0% </td> <td styleCode="Rrule">0.0%</td> <td styleCode="Rrule">0.0%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule" colspan="4" align="left"> <content styleCode="bold">With Metformin (30 Weeks)</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">N</td> <td styleCode="Rrule">113</td> <td styleCode="Rrule">110</td> <td styleCode="Rrule">113</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Overall</td> <td styleCode="Rrule">5.3%</td> <td styleCode="Rrule">4.5%</td> <td styleCode="Rrule">5.3%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Rate (episodes/patient-year)</td> <td styleCode="Rrule">0.12</td> <td styleCode="Rrule">0.13</td> <td styleCode="Rrule">0.12</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Severe</td> <td styleCode="Rrule">0.0% </td> <td styleCode="Rrule">0.0%</td> <td styleCode="Rrule">0.0%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule" colspan="4" align="left"> <content styleCode="bold">With a Sulfonylurea (30 Weeks)</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">N</td> <td styleCode="Rrule">123</td> <td styleCode="Rrule">125</td> <td styleCode="Rrule">129</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Overall</td> <td styleCode="Rrule">3.3%</td> <td styleCode="Rrule">14.4%</td> <td styleCode="Rrule">35.7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Rate (episodes/patient-year)</td> <td styleCode="Rrule">0.07</td> <td styleCode="Rrule">0.64</td> <td styleCode="Rrule">1.61</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Severe</td> <td styleCode="Rrule">0.0% </td> <td styleCode="Rrule">0.0%</td> <td styleCode="Rrule">0.0%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule" colspan="4" align="left"> <content styleCode="bold">With Metformin and a Sulfonylurea (30 Weeks)</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">N</td> <td styleCode="Rrule">247</td> <td styleCode="Rrule">245</td> <td styleCode="Rrule">241</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Overall</td> <td styleCode="Rrule">12.6%</td> <td styleCode="Rrule">19.2%</td> <td styleCode="Rrule">27.8%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Rate (episodes/patient-year)</td> <td styleCode="Rrule">0.58</td> <td styleCode="Rrule">0.78</td> <td styleCode="Rrule">1.71</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Severe</td> <td styleCode="Rrule">0.0% </td> <td styleCode="Rrule">0.4%</td> <td styleCode="Rrule">0.0%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule" colspan="4" align="left"> <content styleCode="bold">With a Thiazolidinedione (16 Weeks)</content> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">N</td> <td styleCode="Rrule">112</td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">121</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Overall</td> <td styleCode="Rrule">7.1%</td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">10.7%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Rate (episodes/patient-years)</td> <td styleCode="Rrule">0.56</td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">0.98</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Severe</td> <td styleCode="Rrule">0.0% </td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">0.0%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule" colspan="4" align="left"> <content styleCode="bold">With Insulin Glargine (30 Weeks) </content> <footnote>When BYETTA was initiated in combination with insulin glargine, the dose of insulin glargine was decreased by 20% in patients with an HbA_1c &#x2264; 8.0 % to minimize the risk of hypoglycemia. See<linkHtml href="#table9"> Table 9 </linkHtml>for insulin dose titration algorithm. </footnote> </td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">N</td> <td styleCode="Rrule">122</td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">137</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">% Overall</td> <td styleCode="Rrule">29.5%</td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">24.8%</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Rate (episodes/patient-years)</td> <td styleCode="Rrule">1.58</td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">1.61</td> </tr> <tr> <td styleCode="Lrule Rrule">% Severe</td> <td styleCode="Rrule">0.8% </td> <td styleCode="Rrule">not evaluated</td> <td styleCode="Rrule">0.0%</td> </tr> </tbody> </table>

<table width="80%" ID="table2"> <caption>Table 2: Treatment-Emergent Adverse Reactions &#x2265;2% Incidence With BYETTA Used as Monotherapy (Excluding Hypoglycemia)<footnote>In a 24-week placebo-controlled trial.</footnote> </caption> <col width="20%" align="center" valign="middle"/> <col width="40%" align="center" valign="middle"/> <col width="40%" align="center" valign="middle"/> <thead> <tr> <th styleCode="Lrule Rrule">Monotherapy</th> <th styleCode="Rrule">Placebo BID N = 77 %</th> <th styleCode="Rrule">All BYETTA BID N = 155 %</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3">BID = twice daily.</td> </tr> </tfoot> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Nausea</td> <td styleCode="Rrule">0</td> <td styleCode="Rrule">8</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Vomiting</td> <td styleCode="Rrule">0</td> <td styleCode="Rrule">4</td> </tr> <tr> <td styleCode="Lrule Rrule">Dyspepsia</td> <td styleCode="Rrule">0</td> <td styleCode="Rrule">3</td> </tr> </tbody> </table>

<table width="80%" ID="table3"> <caption>Table 3: Treatment-Emergent Adverse Reactions &#x2265;2% Incidence and Greater Incidence With BYETTA Treatment Used With Metformin and/or a Sulfonylurea (Excluding Hypoglycemia)<footnote>In three 30-week placebo-controlled clinical trials.</footnote> </caption> <col width="40%" align="center" valign="top"/> <col width="30%" align="center" valign="top"/> <col width="30%" align="center" valign="top"/> <thead> <tr> <th styleCode="Lrule Rrule"/> <th styleCode="Rrule">Placebo BID N = 483 %</th> <th styleCode="Rrule">All BYETTA BID N = 963 %</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3">BID = twice daily.</td> </tr> </tfoot> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Nausea</td> <td styleCode="Rrule">18</td> <td styleCode="Rrule">44</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Vomiting</td> <td styleCode="Rrule">4</td> <td styleCode="Rrule">13</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Diarrhea</td> <td styleCode="Rrule">6</td> <td styleCode="Rrule">13</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Feeling Jittery</td> <td styleCode="Rrule">4</td> <td styleCode="Rrule">9</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Dizziness</td> <td styleCode="Rrule">6</td> <td styleCode="Rrule">9</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Headache</td> <td styleCode="Rrule">6</td> <td styleCode="Rrule">9</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Dyspepsia</td> <td styleCode="Rrule">3</td> <td styleCode="Rrule">6</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Asthenia</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">4</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Gastroesophageal Reflux Disease</td> <td styleCode="Rrule">1</td> <td styleCode="Rrule">3</td> </tr> <tr> <td styleCode="Lrule Rrule">Hyperhidrosis</td> <td styleCode="Rrule">1</td> <td styleCode="Rrule">3</td> </tr> </tbody> </table>