Insulin Degludec

5 WARNINGS AND PRECAUTIONS • Never share an Insulin Degludec FlexTouch pen, insulin syringe, or needle between patients, even if the needle is changed ( 5.1 ). • Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring ( 5.2 ). • Hypoglycemia : May be life-threatening. Increase monitoring with changes to: insulin dosage, concomitant drugs, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness ( 5.3 , 5.4 , 6.1 ). • Hypoglycemia due to medication errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. DO NOT transfer Insulin Degludec from the Insulin Degludec pen into a syringe for administration as overdosage and severe hypoglycemia can result ( 5.4 ). • Hypersensitivity reactions : Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Insulin Degludec, monitor and treat if indicated ( 5.5 ). • Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated ( 5.6 ). • Fluid retention and heart failure with concomitant use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs ( 5.7 ). 5.1 Never Share an Insulin Degludec FlexTouch Pen, Needle, or Insulin Syringe Between Patients Insulin Degludec FlexTouch disposable prefilled pens should never be shared between patients, even if the needle is changed. Patients using Insulin Degludec vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions ( 5.3 )] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ( 6.1 , 6.3 )] . Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, adjustments in concomitant anti-diabetic treatment may be needed [see Dosage and Administration ( 2.4 )] . 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction of insulin, including Insulin Degludec [see Adverse Reactions (6.1)]. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Insulin Degludec, or any insulin, should not be used during episodes of hypoglycemia [see Contraindications ( 4 )]. Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ( 7 )], or who experience recurrent hypoglycemia. The long-acting effect of Insulin Degludec may delay recovery from hypoglycemia compared to shorter-acting insulins. Risk Factors for Hypoglycemia The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin [see Clinical Pharmacology ( 12.2 )] and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Insulin Degludec may vary among different patients or at different times in the same patients and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitant drugs [see Drug Interactions ( 7 )] . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ( 8.6 , 8.7 )] . Risk Mitigation Strategies for Hypoglycemia Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. 5.4 Hypoglycemia Due to Medication Errors Accidental mix-ups between insulin products, have been reported. To avoid medication errors between Insulin Degludec and other insulins, instruct patients to always check the insulin label before each injection. To avoid dosing errors and potential overdose, never use a syringe to remove Insulin Degludec from the Insulin Degludec FlexTouch disposable insulin prefilled pen [see Dosage and Administration ( 2.1 ) and Warnings and Precautions ( 5.3 )] . 5.5 Hypersensitivity Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including Insulin Degludec [see Adverse Reactions ( 6.1 )] . If hypersensitivity reactions occur, discontinue Insulin Degludec; treat per standard of care and monitor until symptoms and signs resolve. Insulin Degludec is contraindicated in patients who have had hypersensitivity reactions to insulin degludec or any of the excipients . 5.6 Hypokalemia All insulins, including Insulin Degludec, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations). 5.7 Fluid Retention and Congestive Heart Failure with Concomitant Use of a PPAR Gamma Agonist Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists can cause dose related fluid retention, when used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Patients treated with insulin, including Insulin Degludec and a PPAR-gamma agonist should be observed for signs and symptoms of congestive heart failure. If congestive heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.

6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere: • Hypoglycemia [see Warnings and Precautions ( 5.3 )] • Hypoglycemia due to Medication errors [see Warnings and Precautions ( 5.4 )] • Hypersensitivity reactions [see Warnings and Precautions ( 5.5 )] • Hypokalemia [see Warnings and Precautions ( 5.6 )] Adverse reactions commonly associated with Insulin Degludec are: • hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema and weight gain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Pharma, Inc. at 1-800-727-6500 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 of Insulin Degludec in subjects with type 1 diabetes or type 2 diabetes was evaluated in nine trials of 6-12 month duration in adults and in one trial of 12-month duration in pediatric patients 1 year of age and older with type 1 diabetes. The cardiovascular safety of Insulin Degludec was evaluated in one double-blinded, event-driven trial of 2-year median duration in patients with type 2 diabetes at high risk of cardiovascular events [see Clinical Studies (14)]. The data in Table 1 reflect the exposure of 1102 adults with type 1 diabetes to Insulin Degludec with a mean exposure duration to Insulin Degludec of 34 weeks in three open-label trials; Study A, B and C [see Clinical Studies (14.1)] . The mean age was 43 years and 1% were older than 75 years. Fifty-seven percent were male, 81% were White, 2% were Black or African American and 4% were Hispanic. The mean body mass index (BMI) was 26 kg/m 2 . The mean duration of diabetes was 18 years and the mean HbA 1c at baseline was 7.8%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported in 11%, 16%, 7% and 0.5% respectively. The mean eGFR at baseline was 87 mL/min/1.73 m 2 and 7% of the patients had an eGFR less than 60 mL/min/1.73 m 2 . The data in Table 2 reflect the exposure of 2713 adults with type 2 diabetes to Insulin Degludec with a mean exposure duration to Insulin Degludec of 36 weeks in six open-label trials; Study D, E, F, G, H and I [see Clinical Studies (14.3)] . The mean age was 58 years and 3% were older than 75 years. Fifty-eight percent were male, 71% were White, 7% were Black or African American and 13% were Hispanic. The mean BMI was 30 kg/m 2 . The mean duration of diabetes was 11 years and the mean HbA 1c at baseline was 8.3%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported for 14%, 10%, 6% and 0.6% of participants respectively. At baseline, the mean eGFR was 83 mL/min/1.73 m 2 and 9% had an eGFR less than 60 mL/min/1.73 m 2 . Common adverse reactions (excluding hypoglycemia) occurring in Insulin Degludec treated subjects during clinical trials in adult patients with type 1 diabetes mellitus and adults with type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively. Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Hypoglycemia is not shown in these tables but discussed in a dedicated subsection below. 174 pediatric patients 1 year of age and older with type 1 diabetes were exposed to Insulin Degludec with a mean exposure to Insulin Degludec of 48 weeks. The mean age was 10 years: 25% were ages 1-5 years, 40% were ages 6-11 years, and 35% were ages 12-17 years. 55% were male, 78% were White, 3% were Black or African American and 4% were Hispanic. The mean body mass index (BMI) was 18.7 kg/m 2 . The mean duration of diabetes was 3.9 years and the mean HbA 1c at baseline was 8.2%. Common adverse reactions in Insulin Degludec treated pediatric patients with type 1 diabetes mellitus were similar to the adverse reactions listed in Table 1. Table 1: Adverse Reactions Occurring in ≥5% of Insulin Degludec-Treated Adult Patients with Type 1 Diabetes Mellitus Adverse Reaction Insulin Degludec (N=1,102) Nasopharyngitis 23.9 % Upper respiratory tract infection 11.9 % Headache 11.8 % Sinusitis 5.1 % Gastroenteritis 5.1 % Table 2: Adverse Reactions Occurring in ≥5% of Insulin Degludec-Treated Adult Patients with Type 2 Diabetes Mellitus Adverse Reaction Insulin Degludec (N=2,713) Nasopharyngitis 12.9 % Headache 8.8 % Upper respiratory tract infection 8.4 % Diarrhea 6.3 % Hypoglycemia Hypoglycemia was the most commonly observed adverse reaction in patients treated with Insulin Degludec. The rates of reported hypoglycemia depended on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for Insulin Degludec with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice. In the open-label adult clinical trials of patients with type 1 and type 2 diabetes, and in the open-label pediatric clinical trial of patients with type 1 diabetes, percentages of adult and pediatric patients with type 1 diabetes randomized to Insulin Degludec who experienced at least one episode of hypoglycemia in clinical trials [see Clinical Studies ( 14 )] and adults with type 2 diabetes are shown in Tables 3 and 4, respectively. Severe hypoglycemia in the open-label trials with adult patients was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe hypoglycemia in the pediatric trial was defined as an altered mental status where the child could not assist in his own care, was semiconscious or unconscious, or in a coma ± convulsions and may require parenteral therapy (glucagon or intravenous glucose). A hypoglycemia episode was defined as a severe hypoglycemia episode or an episode where a laboratory or a self-measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms). Table 3: Percent (%) of Type 1 Diabetes Patients Experiencing at Least One Episode of Severe Hypoglycemia or Hypoglycemia § on Insulin Degludec in Open-Label Adult and Pediatric Clinical Trials Study A Adults + insulin aspart 52 weeks Study B Adults + insulin aspart 26 weeks Study C Adults + insulin aspart 26 weeks Study J Pediatrics + insulin aspart 52 weeks Insulin Degludec (N=472) Insulin Degludec (N=301) Insulin Degludec at the same time each day (N=165) Insulin Degludec at alternating times (N=164) Insulin Degludec (N=174) Severe hypoglycemia* Percent of patients 12.3% 10.6% 12.7% 10.4% 17.8% Hypoglycemia § Percent of patients 95.6% 93.0% 99.4% 93.9% 98.3% * Severe hypoglycemia in pediatric patients: an episode with altered mental status, where the child could not assist in his own care, was semiconscious or unconscious, or in a coma ± convulsions and may require parenteral therapy (glucagon or intravenous glucose). § Hypoglycemia : a severe hypoglycemia episode or an episode where a laboratory or a self-measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms). Table 4: Percent (%) of Patients with Type 2 Diabetes Experiencing at Least One Episode of Severe Hypoglycemia or Hypoglycemia § on Insulin Degludec in Open-Label Adult Clinical Trials Study D + 1-2 OADs* insulin naïve 52 weeks Study E + 1-2 OADs* insulin naïve 26 weeks Study F ± 1-3 OADs* insulin naïve 26 weeks Study G T2DM ± 0-3 OADs* 26 weeks Study H T2DM ± 0-2 OADs* + insulin aspart 52 weeks Study I T2DM ± 1-2 OADs* insulin naïve 26 weeks Insulin Degludec (N=766) Insulin Degludec (N=228) Insulin Degludec (N=284) Insulin Degludec (N=226) Insulin Degludec (alternating time) (N=230) Insulin Degludec (N=753) Insulin Degludec (N=226) Severe Hypoglycemia Percent of patients 0.3% 0 0 0.9% 0.4% 4.5% 0.4% Hypoglycemia § Percent of patients 46.5% 28.5% 50% 43.8% 50.9% 80.9% 42.5% *OAD: oral antidiabetic agent, § Hypoglycemia : a severe hypoglycemia episode or an episode where a laboratory or a self-measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms). Hypersensitivity Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock have occurred with insulin, including Insulin Degludec and may be life threatening. Hypersensitivity (manifested with swelling of tongue and lips, diarrhea, nausea, tiredness, and itching) and urticaria were reported in 0.9% of patients treated with Insulin Degludec. Lipodystrophy Long-term use of insulin, including Insulin Degludec, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue) and may affect insulin absorption [see Dosage and Administration ( 2.1 )] . In the clinical program, lipodystrophy, lipohypertrophy, or lipoatrophy was reported in 0.3% of patients treated with Insulin Degludec. Injection Site Reactions Patients taking Insulin Degludec may experience injection site reactions, including injection site hematoma, pain, hemorrhage, erythema, nodules, swelling, discoloration, pruritus, warmth, and injection site mass. In the clinical program, injection site reactions occurred in 3.8% of patients treated with Insulin Degludec. Weight Gain Weight gain can occur with insulin therapy, including Insulin Degludec, and has been attributed to the anabolic effects of insulin. In the clinical program after 52 weeks of treatment, patients with type 1 diabetes treated with Insulin Degludec gained an average of 1.8 kg and patients with type 2 diabetes treated with Insulin Degludec gained an average of 3.0 kg. Peripheral Edema Insulin Degludec may cause sodium retention and edema. In the clinical program, peripheral edema occurred in 0.9% of patients with type 1 diabetes mellitus and 3.0% of patients with type 2 diabetes mellitus treated with Insulin Degludec. 6.2 Immunogenicity As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to Insulin Degludec with the incidence of antibodies in other studies or to other products may be misleading. In a 52-week trial of adult insulin-experienced type 1 diabetes patients, 68.9% of patients who received Insulin Degludec were positive at baseline for anti-insulin degludec antibodies and 12.3% of the patients developed anti-insulin degludec antibodies at least once during the trial. In a 52-week trial of pediatric insulin-experienced type 1 diabetes patients, 84.1% of patients who received Insulin Degludec were positive at baseline for anti-insulin degludec antibodies and 5.8% of patients developed anti-insulin degludec antibodies at least once during the trial. In a 52-week trial of adult insulin-naïve type 2 diabetes patients, 1.7% of patients who received Insulin Degludec were positive at baseline for anti-insulin degludec antibodies and 6.2% of patients developed anti-insulin degludec antibodies at least once during the trial. In these trials, between 96.7% and 99.7% of patients who were positive for anti-insulin degludec antibodies were also positive for anti-human insulin antibodies. 6.3 Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of Insulin Degludec. 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. Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

<table width="100%"><col width="51%"/><col width="49%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Insulin Degludec</content></paragraph><paragraph><content styleCode="bold">(N=1,102)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nasopharyngitis</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23.9 %</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Upper respiratory tract infection</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11.9 %</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11.8 %</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sinusitis</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.1 %</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Gastroenteritis</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5.1 %</paragraph></td></tr></tbody></table>

<table width="100%"><col width="51%"/><col width="49%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">Adverse Reaction</content></paragraph></td><td align="center" styleCode="Rrule Botrule Toprule " valign="top"><paragraph><content styleCode="bold">Insulin Degludec </content></paragraph><paragraph><content styleCode="bold">(N=2,713)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nasopharyngitis</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12.9 %</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8.8 %</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Upper respiratory tract infection</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8.4 %</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6.3 %</paragraph></td></tr></tbody></table>

<table width="100%"><col width="13%"/><col width="17%"/><col width="16%"/><col width="11%"/><col width="16%"/><col width="26%"/><thead><tr><th align="left" styleCode="Rrule Botrule Lrule Toprule " valign="top"/><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><content styleCode="bold">Study A</content> <content styleCode="bold">Adults</content> <content styleCode="bold">+ insulin aspart</content> <content styleCode="bold">52 weeks</content></th><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><content styleCode="bold">Study B</content> <content styleCode="bold">Adults</content> <content styleCode="bold">+ insulin aspart</content> <content styleCode="bold">26 weeks</content></th><th align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><content styleCode="bold">Study C</content> <content styleCode="bold">Adults</content> <content styleCode="bold">+ insulin aspart</content> <content styleCode="bold">26 weeks</content></th><th align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><content styleCode="bold">Study J</content> <content styleCode="bold">Pediatrics</content> <content styleCode="bold">+ insulin aspart</content> <content styleCode="bold">52 weeks</content></th></tr><tr><th align="left" styleCode="Rrule Lrule Botrule " valign="top"/><th align="center" styleCode="Rrule Lrule Botrule " valign="middle"><content styleCode="bold">Insulin Degludec</content> <content styleCode="bold">(N=472)</content></th><th align="center" styleCode="Rrule Lrule Botrule " valign="middle"><content styleCode="bold">Insulin Degludec</content> <content styleCode="bold">(N=301)</content></th><th align="center" styleCode="Rrule Lrule Botrule " valign="middle"><content styleCode="bold">Insulin Degludec at the same time each day</content> <content styleCode="bold">(N=165)</content></th><th align="center" styleCode="Rrule Lrule Botrule " valign="middle"><content styleCode="bold">Insulin Degludec at alternating times</content> <content styleCode="bold">(N=164)</content></th><th align="center" styleCode="Rrule Lrule Botrule " valign="top"><content styleCode="bold">Insulin Degludec</content> <content styleCode="bold">(N=174)</content></th></tr></thead><tbody><tr><td colspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Severe hypoglycemia*</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Percent of patients</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>12.3%</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>10.6%</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>12.7%</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="middle"><paragraph>10.4%</paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph>17.8%</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Hypoglycemia^&#xA7;</content></paragraph></td><td styleCode="Rrule Lrule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph>Percent of patients</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>95.6%</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>93.0%</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>99.4%</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="middle"><paragraph>93.9%</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="top"><paragraph>98.3%</paragraph></td></tr></tbody></table>