FDA label e4b84cab-749a-54c9-e053-2995a90aa154

5 WARNINGS AND PRECAUTIONS Never share a HUMALOG prefilled pen, cartridge, reusable pen compatible with Lilly 3 mL cartridges, or syringe 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. Monitor blood glucose and increase monitoring frequency with changes to insulin dosage, use of glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. ( 5.3 , 7 , 8.6 , 8.7 ) Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. Do not transfer HUMALOG U-200 from the HUMALOG KwikPen to a syringe as overdosage and severe hypoglycemia can result. ( 5.4 ) Hypersensitivity Reactions: May be life-threatening. Discontinue HUMALOG, monitor and treat if indicated. ( 5.5 ) Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of 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 ) Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Monitor glucose and administer HUMALOG U-100 by subcutaneous injection if pump malfunction occurs. ( 5.8 ) 5.1 Never Share a HUMALOG Prefilled Pen, Cartridge, Reusable Pen Compatible with Lilly 3 mL Cartridges 1 , or Syringe Between Patients HUMALOG prefilled pens, cartridges, and reusable pens compatible with Lilly 3 mL cartridges must never be shared between patients, even if the needle is changed. Patients using HUMALOG vials must 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 )] . 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, dosage adjustments of concomitant antidiabetic products may be needed. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulins, including HUMALOG. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ( 7 )] , or in patients who experience recurrent hypoglycemia. Risk Factors for Hypoglycemia The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin preparations, the glucose lowering effect time course of HUMALOG may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology ( 12.2 )] . 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 co-administered medication [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 basal insulin products and other insulins, particularly rapid-acting insulins, have been reported. To avoid medication errors between HUMALOG and other insulins, instruct patients to always check the insulin label before each injection. Do not transfer HUMALOG U-200 from the HUMALOG KwikPen to a syringe. The markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia [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 insulin products, including HUMALOG. If hypersensitivity reactions occur, discontinue HUMALOG; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions ( 6.1 )] . HUMALOG is contraindicated in patients who have had hypersensitivity reactions to HUMALOG or any of its excipients [see Contraindications ( 4 )] . 5.6 Hypokalemia All insulin products, including HUMALOG, 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 Heart Failure with Concomitant Use of PPAR-gamma Agonists Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including HUMALOG, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If 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. 5.8 Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with HUMALOG may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see How Supplied/Storage and Handling ( 16.2 ) and Patient Counseling Information ( 17 )] .

6 ADVERSE REACTIONS Adverse reactions associated with HUMALOG include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Observed with HUMALOG U-100 The following adverse reactions are discussed elsewhere: Hypoglycemia [see Warnings and Precautions ( 5.3 )] . Hypokalemia [see Warnings and Precautions ( 5.6 )] . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared with those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice. The frequencies of Treatment-Emergent Adverse Events during HUMALOG clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below. Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 Diabetes Mellitus (adverse events with frequency ≥5%) Events, n (%) Lispro (n=81) Regular human insulin (n=86) Flu syndrome 28 (34.6) 28 (32.6) Pharyngitis 27 (33.3) 29 (33.7) Rhinitis 20 (24.7) 25 (29.1) Headache 24 (29.6) 19 (22.1) Pain 16 (19.8) 14 (16.3) Cough increased 14 (17.3) 15 (17.4) Infection 11 (13.6) 18 (20.9) Nausea 5 (6.2) 13 (15.1) Accidental injury 7 (8.6) 10 (11.6) Surgical procedure 5 (6.2) 12 (14.0) Fever 5 (6.2) 10 (11.6) Abdominal pain 6 (7.4) 7 (8.1) Asthenia 6 (7.4) 7 (8.1) Bronchitis 6 (7.4) 6 (7.0) Diarrhea 7 (8.6) 5 (5.8) Dysmenorrhea 5 (6.2) 6 (7.0) Myalgia 6 (7.4) 5 (5.8) Urinary tract infection 5 (6.2) 4 (4.7) Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 Diabetes Mellitus (adverse events with frequency ≥5%) Events, n (%) Lispro (n=714) Regular human insulin (n=709) Headache 83 (11.6) 66 (9.3) Pain 77 (10.8) 71 (10.0) Infection 72 (10.1) 54 (7.6) Pharyngitis 47 (6.6) 58 (8.2) Rhinitis 58 (8.1) 47 (6.6) Flu syndrome 44 (6.2) 58 (8.2) Surgical procedure 53 (7.4) 48 (6.8) Insulin initiation and intensification of glucose control Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy. Lipodystrophy Long-term use of insulin, including HUMALOG, can cause lipodystrophy at the site of repeated insulin injections or infusion. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection or infusion sites within the same region to reduce the risk of lipodystrophy [see Dosage and Administration ( 2.2 )] . Weight gain Weight gain can occur with insulin therapy, including HUMALOG, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. Peripheral Edema Insulin, including HUMALOG, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Adverse Reactions with Continuous Subcutaneous Insulin Infusion (CSII) — HUMALOG U-100 In a 12-week, randomized, crossover study in adult patients with type 1 diabetes (n=39), the rates of catheter occlusions and infusion site reactions were similar for HUMALOG U-100 and regular human insulin treated patients ( see Table 3 ). Table 3: Catheter Occlusions and Infusion Site Reactions HUMALOG U-100 (n=38) Regular human insulin (n=39) Catheter occlusions/month 0.09 0.10 Infusion site reactions 2.6% (1/38) 2.6% (1/39) In a randomized, 16-week, open-label, parallel design study of children and adolescents with type 1 diabetes, adverse event reports related to infusion-site reactions were similar for insulin lispro and insulin aspart (21% of 100 patients versus 17% of 198 patients, respectively). In both groups, the most frequently reported infusion site adverse events were infusion site erythema and infusion site reaction. Allergic Reactions Local Allergy — As with any insulin therapy, patients taking HUMALOG may experience redness, swelling, or itching at the site of the injection. These minor reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation of HUMALOG. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique. Systemic Allergy — Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including HUMALOG. Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis. In controlled clinical trials, pruritus (with or without rash) was seen in 17 patients receiving regular human insulin (n=2969) and 30 patients receiving HUMALOG (n=2944). Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in HUMALOG [see Contraindications ( 4 )] . Antibody Production In large clinical trials with patients with type 1 (n=509) and type 2 (n=262) diabetes mellitus, anti-insulin antibody (insulin lispro-specific antibodies, insulin-specific antibodies, cross-reactive antibodies) formation was evaluated in patients receiving both regular human insulin and HUMALOG (including patients previously treated with human insulin and naive patients). As expected, the largest increase in the antibody levels occurred in patients new to insulin therapy. The antibody levels peaked by 12 months and declined over the remaining years of the study. These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose. There was no statistically significant relationship between the change in the total daily insulin dose and the change in percent antibody binding for any of the antibody types. 6.2 Postmarketing Experience 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Regulation of glucose metabolism is the primary activity of insulins and insulin analogs, including insulin lispro. Insulins lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis and proteolysis, and enhance protein synthesis. 12.2 Pharmacodynamics HUMALOG has been shown to be equipotent to human insulin on a molar basis. One unit of HUMALOG has the same glucose-lowering effect as one unit of regular human insulin. Studies in normal volunteers and patients with diabetes demonstrated that HUMALOG has a more rapid onset of action and a shorter duration of activity than regular human insulin when given subcutaneously. The time course of action of insulin and insulin analogs, such as HUMALOG, may vary considerably in different individuals or within the same individual. The parameters of HUMALOG activity (time of onset, peak time, and duration) as designated in Figure 1 should be considered only as general guidelines. The rate of insulin absorption, and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables [see Warnings and Precautions ( 5.2 )] . a Baseline insulin concentration was maintained by infusion of 0.2 mU/min/kg human insulin. Intravenous Administration of HUMALOG U-100 — The glucose lowering effect of intravenously administered HUMALOG was tested in 21 patients with type 1 diabetes. For the study, the patients' usual doses of insulin were held and blood glucose concentrations were allowed to reach a stable range of 200 to 260 mg/dL during a one to three hours run-in phase. The run-in phase was followed by a 6-hour assessment phase. During the assessment phase, patients received intravenous HUMALOG at an initial infusion rate of 0.5 units/hour. The infusion rate of HUMALOG could be adjusted at regular timed intervals to achieve and maintain blood glucose concentrations between 100 to 160 mg/dL. The mean blood glucose levels during the assessment phase for patients on HUMALOG therapy are summarized below in Table 4 . All patients achieved the targeted glucose range at some point during the 6-hour assessment phase. At the endpoint, blood glucose was within the target range (100 to 160 mg/dL) for 17 of 20 patients treated with HUMALOG. The average time (±SE) required to attain near normoglycemia was 129 ± 14 minutes for HUMALOG. Table 4: Mean Blood Glucose Concentrations (mg/dL) During Intravenous Infusions of HUMALOG U-100 a Results shown as mean ± SD Time from Start of Infusion (minutes) Mean Blood Glucose (mg/dL) Intravenous a 0 224 ± 16 30 205 ± 21 60 195 ± 20 120 165 ± 26 180 140 ± 26 240 123 ± 20 300 120 ± 27 360 122 ± 25 The pharmacodynamics of a single 20 unit dose of HUMALOG U-200 administered subcutaneously were compared to the pharmacodynamics of a single 20 unit dose of HUMALOG U-100 administered subcutaneously in a euglycemic clamp study enrolling healthy subjects. In this study, the overall, maximum, and time to maximum glucose lowering effect were similar between HUMALOG U-200 and HUMALOG U-100. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) were 125 g and 126 g for HUMALOG U-200 and HUMALOG U-100, respectively. The maximum glucose infusion rate was 534 mg/min and 559 mg/min and the corresponding median time (min, max) to maximum effect were 2.8 h (0.5 h – 6.3 h) and 2.4 h (0.5 h – 4.7 h) for HUMALOG U-200 and HUMALOG U-100, respectively. 12.3 Pharmacokinetics Absorption and Bioavailability — Studies in healthy volunteers and patients with diabetes demonstrated that HUMALOG is absorbed more quickly than regular human insulin. In healthy volunteers given subcutaneous doses of HUMALOG ranging from 0.1 to 0.4 unit/kg, peak serum levels were seen 30 to 90 minutes after dosing. When healthy volunteers received equivalent doses of regular human insulin, peak insulin levels occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes a Baseline insulin concentration was maintained by infusion of 0.2 mU/min/kg human insulin. HUMALOG U-100 was absorbed at a consistently faster rate than regular human insulin in healthy male volunteers given 0.2 unit/kg at abdominal, deltoid, or femoral subcutaneous sites. After HUMALOG was administered in the abdomen, serum drug levels were higher and the duration of action was slightly shorter than after deltoid or thigh administration. Bioavailability of HUMALOG is similar to that of regular human insulin. The absolute bioavailability after subcutaneous injection ranges from 55% to 77% with doses between 0.1 to 0.2 unit/kg, inclusive. The results of a study in healthy subjects demonstrated that HUMALOG U-200 is bioequivalent to HUMALOG U-100 following administration of a single 20 unit dose. The mean observed area under the serum insulin concentration-time curve from time zero to infinity was 2360 pmol hr/L and 2390 pmol hr/L for HUMALOG U-200 and HUMALOG U-100, respectively. The corresponding mean peak serum insulin concentration was 795 pmol/L and 909 pmol/L for HUMALOG U-200 and HUMALOG U-100, respectively. The median time to maximum concentration was 1.0 hour for both formulations. Distribution — When administered intravenously as bolus injections of 0.1 and 0.2 U/kg dose in two separate groups of healthy subjects, the mean volume of distribution of HUMALOG appeared to decrease with increase in dose (1.55 and 0.72 L/kg, respectively) in contrast to that of regular human insulin for which, the volume of distribution was comparable across the two dose groups (1.37 and 1.12 L/kg for 0.1 and 0.2 U/kg dose, respectively). Metabolism — Human metabolism studies have not been conducted. However, animal studies indicate that the metabolism of HUMALOG is identical to that of regular human insulin. Elimination — After subcutaneous administration of HUMALOG, the t 1/2 is shorter than that of regular human insulin (1 versus 1.5 hours, respectively). When administered intravenously, HUMALOG and regular human insulin demonstrated similar dose-dependent clearance, with a mean clearance of 21.0 mL/min/kg and 21.4 mL/min/kg, respectively (0.1 unit/kg dose), and 9.6 mL/min/kg and 9.4 mL/min/kg, respectively (0.2 unit/kg dose). Accordingly, HUMALOG demonstrated a mean t 1/2 of 0.85 hours (51 minutes) and 0.92 hours (55 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses, and regular human insulin mean t 1/2 was 0.79 hours (47 minutes) and 1.28 hours (77 minutes), respectively for 0.1 unit/kg and 0.2 unit/kg doses. Specific Populations The effects of age, gender, race, obesity, pregnancy, or smoking on the pharmacokinetics of HUMALOG have not been studied. Renal Impairment — Type 2 diabetic patients with varying degree of renal impairment showed no difference in pharmacokinetics of regular insulin and HUMALOG. However, the sensitivity of the patients to insulin did change, with an increased response to insulin as the renal function declined. Some studies with human insulin have shown increased circulating levels of insulin in patients with renal impairment. Careful glucose monitoring and dose adjustments of insulin, including HUMALOG, may be necessary in patients with renal dysfunction. Hepatic Impairment — Type 2 diabetic patients with impaired hepatic function showed no effect on the pharmacokinetics of HUMALOG as compared to patients with no hepatic dysfunction. However, some studies with human insulin have shown increased circulating levels of insulin in patients with liver failure. Careful glucose monitoring and dose adjustments of insulin, including HUMALOG, may be necessary in patients with hepatic dysfunction. HUMALOG U-100 The following additional adverse reactions have been identified during post-approval use of HUMALOG. 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. Medication errors in which other insulins have been accidentally substituted for HUMALOG have been identified during post-approval use [see Patient Counseling Information ( 17 )] . 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 ID="t1" width="100%"><caption>Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 Diabetes Mellitus (adverse events with frequency &#x2265;5%) </caption><col width="32.223%" align="left"/><col width="33.889%" align="left"/><col width="33.889%" align="left"/><tbody><tr><td align="center" styleCode="Toprule Botrule Lrule Rrule" valign="top"><content styleCode="bold">Events, n (%)</content></td><td align="center" styleCode="Toprule Botrule Rrule" valign="top"><content styleCode="bold">Lispro (n=81) </content></td><td align="center" styleCode="Toprule Botrule Rrule" valign="top"><content styleCode="bold">Regular human insulin (n=86) </content></td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Flu syndrome </td><td align="center" styleCode="Botrule Rrule" valign="top">28 (34.6) </td><td align="center" styleCode="Botrule Rrule" valign="top">28 (32.6) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Pharyngitis </td><td align="center" styleCode="Botrule Rrule" valign="top">27 (33.3) </td><td align="center" styleCode="Botrule Rrule" valign="top">29 (33.7) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Rhinitis </td><td align="center" styleCode="Botrule Rrule" valign="top">20 (24.7) </td><td align="center" styleCode="Botrule Rrule" valign="top">25 (29.1) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Headache </td><td align="center" styleCode="Botrule Rrule" valign="top">24 (29.6) </td><td align="center" styleCode="Botrule Rrule" valign="top">19 (22.1) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Pain </td><td align="center" styleCode="Botrule Rrule" valign="top">16 (19.8) </td><td align="center" styleCode="Botrule Rrule" valign="top">14 (16.3) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Cough increased </td><td align="center" styleCode="Botrule Rrule" valign="top">14 (17.3) </td><td align="center" styleCode="Botrule Rrule" valign="top">15 (17.4) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Infection </td><td align="center" styleCode="Botrule Rrule" valign="top">11 (13.6) </td><td align="center" styleCode="Botrule Rrule" valign="top">18 (20.9) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Nausea </td><td align="center" styleCode="Botrule Rrule" valign="top">5 (6.2) </td><td align="center" styleCode="Botrule Rrule" valign="top">13 (15.1) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Accidental injury </td><td align="center" styleCode="Botrule Rrule" valign="top">7 (8.6) </td><td align="center" styleCode="Botrule Rrule" valign="top">10 (11.6) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Surgical procedure </td><td align="center" styleCode="Botrule Rrule" valign="top">5 (6.2) </td><td align="center" styleCode="Botrule Rrule" valign="top">12 (14.0) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Fever </td><td align="center" styleCode="Botrule Rrule" valign="top">5 (6.2) </td><td align="center" styleCode="Botrule Rrule" valign="top">10 (11.6) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Abdominal pain </td><td align="center" styleCode="Botrule Rrule" valign="top">6 (7.4) </td><td align="center" styleCode="Botrule Rrule" valign="top">7 (8.1) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Asthenia </td><td align="center" styleCode="Botrule Rrule" valign="top">6 (7.4) </td><td align="center" styleCode="Botrule Rrule" valign="top">7 (8.1) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Bronchitis </td><td align="center" styleCode="Botrule Rrule" valign="top">6 (7.4) </td><td align="center" styleCode="Botrule Rrule" valign="top">6 (7.0) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Diarrhea </td><td align="center" styleCode="Botrule Rrule" valign="top">7 (8.6) </td><td align="center" styleCode="Botrule Rrule" valign="top">5 (5.8) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Dysmenorrhea </td><td align="center" styleCode="Botrule Rrule" valign="top">5 (6.2) </td><td align="center" styleCode="Botrule Rrule" valign="top">6 (7.0) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Myalgia </td><td align="center" styleCode="Botrule Rrule" valign="top">6 (7.4) </td><td align="center" styleCode="Botrule Rrule" valign="top">5 (5.8) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Urinary tract infection </td><td align="center" styleCode="Botrule Rrule" valign="top">5 (6.2) </td><td align="center" styleCode="Botrule Rrule" valign="top">4 (4.7) </td></tr></tbody></table>

<table ID="t2" width="100%"><caption>Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 Diabetes Mellitus (adverse events with frequency &#x2265;5%) </caption><col width="32.233%" align="left"/><col width="33.867%" align="left"/><col width="33.900%" align="left"/><tbody><tr><td align="center" styleCode="Toprule Botrule Lrule Rrule" valign="top"><content styleCode="bold">Events, n (%)</content></td><td align="center" styleCode="Toprule Botrule Rrule" valign="top"><content styleCode="bold">Lispro (n=714) </content></td><td align="center" styleCode="Toprule Botrule Rrule" valign="top"><content styleCode="bold">Regular human insulin (n=709) </content></td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Headache </td><td align="center" styleCode="Botrule Rrule" valign="top">83 (11.6) </td><td align="center" styleCode="Botrule Rrule" valign="top">66 (9.3) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Pain </td><td align="center" styleCode="Botrule Rrule" valign="top">77 (10.8) </td><td align="center" styleCode="Botrule Rrule" valign="top">71 (10.0) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Infection </td><td align="center" styleCode="Botrule Rrule" valign="top">72 (10.1) </td><td align="center" styleCode="Botrule Rrule" valign="top">54 (7.6) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Pharyngitis </td><td align="center" styleCode="Botrule Rrule" valign="top">47 (6.6) </td><td align="center" styleCode="Botrule Rrule" valign="top">58 (8.2) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Rhinitis </td><td align="center" styleCode="Botrule Rrule" valign="top">58 (8.1) </td><td align="center" styleCode="Botrule Rrule" valign="top">47 (6.6) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Flu syndrome </td><td align="center" styleCode="Botrule Rrule" valign="top">44 (6.2) </td><td align="center" styleCode="Botrule Rrule" valign="top">58 (8.2) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Surgical procedure </td><td align="center" styleCode="Botrule Rrule" valign="top">53 (7.4) </td><td align="center" styleCode="Botrule Rrule" valign="top">48 (6.8) </td></tr></tbody></table>

<table ID="t3" width="100%"><caption>Table 3: Catheter Occlusions and Infusion Site Reactions </caption><col width="33.000%" align="left"/><col width="34.000%" align="left"/><col width="33.000%" align="left"/><tbody><tr><td align="left" styleCode="Toprule Botrule Lrule Rrule" valign="top"/><td align="center" styleCode="Toprule Botrule Rrule" valign="top">HUMALOG U-100 (n=38) </td><td align="center" styleCode="Toprule Botrule Rrule" valign="top">Regular human insulin (n=39) </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Catheter occlusions/month </td><td align="center" styleCode="Botrule Rrule" valign="top">0.09 </td><td align="center" styleCode="Botrule Rrule" valign="top">0.10 </td></tr><tr><td align="left" styleCode="Botrule Lrule Rrule" valign="top">Infusion site reactions </td><td align="center" styleCode="Botrule Rrule" valign="top">2.6% (1/38) </td><td align="center" styleCode="Botrule Rrule" valign="top">2.6% (1/39) </td></tr></tbody></table>