Consider Humalog for your patients with diabetes who:

Need rapid-acting insulin, in addition to long-acting insulin, to manage postmeal glucose levels
Need to add mealtime insulin injections to current basal insulin injections
In your opinion are appropriate for this treatment plan
Are ready to start mealtime insulin
Want an insulin regimen that allows flexibility around family meals

Dosage of Humalog must be individualized. Humalog given by subcutaneous injection should generally be used in regimens with intermediate- or long-acting insulins.

Select Important Safety Information

Humalog and Insulin Lispro Injection are contraindicated during episodes of hypoglycemia and in patients who are hypersensitive to these insulins or any of their excipients.

In patients with Type 1 Diabetes:

Humalog U-100 reduced postprandial blood glucose compared to regular human insulin^*1,2

In pediatric patients, Humalog reduced PPG to a greater extent than regular insulin; A1C did not differ between patients treated with regular insulin and those treated with Humalog.^3,4

Study Design³

61 children (2.9 to 11.4 years), mean baseline A1C 8.4% ± 1.0%

Diagnosed ≥12 months earlier
Receiving human basal insulin (NPH, lente, or ultralente) plus human regular insulin (≥2 months prior to randomization)

3-way crossover study

3 treatment regimens
1. Humalog immediately postmeal
2. Humalog 15 minutes premeal
3. Regular human insulin 30-45 minutes premeal
Prestudy basal insulin regimen continued during study
All patients received all 3 treatment regimens for 3 months per regimen in a crossover design
Mean total daily insulin dose for all treatments was 0.8 U/kg/day
No difference in A1C or rate of hypoglycemia among the 3 therapies

Insulin lispro administered 15 minutes compared with regular human insulin administered 30-45 minutes before meals lowered postprandial glucose after breakfast (11.7 mmol/L vs 15.0 mmol/L; p>.001) and the evening meal (8.8 mmol/L vs 10.8 mmol/L; p=.006).³ Insulin lispro administered before meals compared with regular human insulin administered 30-45 minutes before meals resulted in lower postprandial glucose after breakfast (9.7 mmol/L vs 10.6 mmol/L; p>.001) and the evening meal (8.6 mmol/L and 9.3 mmol/L, p=.003) in adolescents with type 1 diabetes.⁴

Select Safety Information

Humalog has not been studied in children with type 1 diabetes less than 3 years of age or in children with type 2 diabetes.

Never share a Humalog or Insulin Lispro Injection prefilled pen, cartridge, reusable pen compatible with Lilly 3 mL cartridges, or syringe between patients as it poses a risk for transmission of blood-borne pathogens.

In patients with Type 1 Diabetes:

Humalog U-100 provided improved glycemic control when used in an external insulin pump⁵

Humalog effectively improved A1C and blood glucose stability in patients with type 1 diabetes using insulin pumps.^5,6,7 Humalog in an external insulin pump is approved for use in children with type 1 diabetes 4 years of age and older.

Adult Pump Use

In a 24-week, open-label, randomized, crossover multicenter study (N=39), using Humalog effectively improved A1C and blood glucose stability in patients using insulin pumps when compared to regular human insulin.⁶ The use of Humalog significantly reduced A1C and postprandial glucose levels, without increasing hypoglycemic episodes.⁶ See full study design and results below.

Administer Humalog U-100 by continuous subcutaneous infusion using an insulin pump. Do NOT mix Humalog U-100 with other insulins when administering using a continuous subcutaneous infusion pump.

Pediatric Pump Use

In a 16-week, open-label, parallel-group, multicenter study of children and adolescents with type 1 diabetes (N=298) aged 4 to 18 years, Humalog demonstrated comparable changes from baseline A1C and comparable rates of hypoglycemia as insulin aspart.⁷ See study design below.

Only the U-100 formulation of Humalog is approved for use in children age 3 or older by continuous subcutaneous infusion in insulin pumps.

Humalog has not been studied in pediatric patients younger than 3 years of age.

Humalog has not been studied in pediatric patients with type 2 diabetes.

Pediatric Insulin Pump Study in Type 1 Diabetes (16 weeks; n=298)

	Humalog	Aspart
N	Humalog 100	Aspart 198
Baseline A1C (%)^*	Humalog 8.2 ± 0.8	Aspart 8.0 ± 0.9
Change from baseline A1C (%)	Humalog -0.1 ± 0.7	Aspart -0.1 ± 0.8
Treatment difference in A1C, mean (95% confidence interval)	Humalog Aspart 0.1(-0.3, 0.1)
Baseline insulin dose (units/kg/24 hours)^*	Humalog 0.9 ± 0.3	Aspart 0.9 ± 0.3
End-of-study insulin dose (units/kg/24 hours)^*	Humalog 0.9 ± 0.2	Aspart 0.9 ± 0.2
Patients with severe hypoglycemia (n, %)^†	Humalog 8 (8%)	Aspart 19 (10%)

^*Values are mean ± SD.
^†Severe hypoglycemia refers to hypoglycemia associated with central nervous system symptoms and requiring the intervention of another person or hospitalization.

Adult Pump Use Full Study Design and Results

A randomized, crossover, open-label study (N=39) compared insulin lispro (IL) with regular human insulin (U-100) in patients with type 1 diabetes mellitus (mean age 39). Both were administered in an insulin pump (MiniMed 506). Each treatment was given for 3 months and then switched to the other for 3 months. In the IL cohort, the A1C decreased from 7.74 ± 0.20% at baseline to 7.11 ± 0.15% at 12 weeks of period 1. The U-100 cohort showed a decrease in A1C from 7.97 ± 0.13 to 7.88 ± 0.16%; the difference between IL and U-100 was significant (p=.01). Mean daily and 2-hour postprandial blood glucose was also significantly lower in the IL than U-100 cohort (p<.0001). The rate of hypoglycemia determined in the last 30 days of the first treatment period was 7.03 versus 7.94 events/month with IL and U-100, respectively.⁶ In a second study, 113 subjects (mean age 37.1 years) with type 1 diabetes mellitus were treated with IL or U-100 administered by continuous subcutaneous insulin infusion. The study was a randomized, crossover design in which each treatment was administered for 4 months. The baseline A1C was 7.24% and decreased to 6.77 ± 0.88% and 6.90 ± 0.97% in the IL and U-100 cohorts, respectively (p<.02). The postprandial glucose was reduced after breakfast (run-in 8.5 to 7.0 and 8.6 mmol/L), lunch (8.4 to 7.6 and 8.7 mmol/L), and dinner (8.2 to 7.6 and 8.3 mmol/L) in IL and U-100 cohorts, respectively (all p<.001). The total number of hypoglycemia episodes per patient was not significantly different between treatments (12.4 versus 11.0 in the IL and U-100 cohorts, respectively).⁸

Pediatric Pump Use Study Design and Results

In a 16-week, parallel-group, open-label, multicenter study, children and adolescents with type 1 diabetes were randomly assigned to insulin aspart (n=198) or insulin lispro (n=100) administered by continuous subcutaneous insulin infusion.⁷ Approximately two-thirds of subjects in each treatment arm were aged 12-18 years. The A1C change from baseline to endpoint for insulin aspart and insulin lispro was 0.15% and 0.05%, respectively. Insulin aspart was noninferior to insulin lispro as the 95% CI for the difference in treatment did not exceed 0.4 (95% CI -0.27 to 0.07%). In general, the incidence and rate of hypoglycemia were similar between insulin aspart and insulin lispro. At least one major hypoglycemic event occurred in 9.6% of aspart and 8.0% of lispro subjects.

Important information about using Humalog U-100 in an insulin pump

Humalog should not be diluted or mixed with any other insulin when used in an external insulin pump. Change reservoir at least every 7 days. Change the infusion set and insertion site at least every 3 days.

Adverse reactions associated with Humalog in patients receiving continuous subcutaneous insulin infusion: in adult patients, catheter occlusions (0.09/month), infusion-site reactions (2.6%). In children and adolescents, infusion-site reactions (21%).

Select Important Safety Information

Malfunction of the insulin pump device, infusion set, or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Patients using subcutaneous insulin infusion pumps must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.

In Adult Patients with Type 2 Diabetes:

Humalog dosed 15 minutes before or immediately after meals when added to a basal insulin:

Reduced postprandial glucose levels^1,2
Lowered A1C

Compared to regular human insulin, Humalog U-100 lowered 2-hour postprandial glucose excursions

^*In a study of 722 patients with type 2 diabetes, the increase in serum glucose levels at 2 hours following the test meal was 53% lower for Humalog relative to regular human insulin (p<.001). Actual values for the rise in glucose were 25.4 ± 1.8 mg/dL for Humalog vs 54.0 ± 1.8 mg/dL for regular human insulin.²

Select Important Safety Information

Changes in insulin regimen (e.g. insulin strength, manufacturer, type, injection site, or method of administration) may affect glycemic control and predispose patients to hypoglycemia and hyperglycemia. Make changes cautiously with increased frequency of blood glucose monitoring.

References: 1. Anderson JH, Brunelle RL, Koivisto VA. Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter insulin lispro study group. Diabetes. 1997;46(2):265-270. 2. Anderson JH Jr, Brunelle RL, Keohane P, et al; Multicenter Insulin Lispro Study Group. Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Arch Intern Med. 1997;157(11):1249-1255. 3. Deeb LD, Holcombe JH, Brunelle R, et al. Insulin lispro lowers postprandial glucose in prepubertal children with diabetes. Pediatrics. 2001;108:1175-1179. 4. Holcombe JH, Zalani S, Arora VK, Mast CJ. Comparison of insulin lispro with regular human insulin for the treatment of type 1 diabetes in adolescents. Clin Ther. 2002;24:629-638. 5. Humalog [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC. 6. Melki V, Renard E, Lassmann-Vague V, et al. Improvement of HbA1C and blood glucose stability in IDDM patients treated with lispro insulin analog in external pumps. Diabetes Care. 1998;21(6):977-982. 7. Weinzimer SA, Ternand, C, Howard C, et al. Insulin Aspart Pediatric Pump Study Group. A randomized trial comparing continuous subcutaneous insulin infusion of insulin aspart versus insulin lispro in children and adolescents with type 1 diabetes. Diabetes Care. 2008;31(2):210-215. 8. Renner R, Pfützner A, Trautmann M, et al. German Humalog-CSII Study Group. Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. Diabetes Care. 1999;22(5):784-788.

IMPORTANT SAFETY INFORMATION

Humalog, Insulin Lispro Injection, Humalog Mix75/25, Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25, and Humalog Mix50/50 are contraindicated during episodes of hypoglycemia and in patients who are hypersensitive to these insulins or any of their excipients.

Never share a Humalog or Insulin Lispro Injection prefilled pen, cartridge, reusable pen compatible with Lilly 3 mL cartridges, or syringe between patients, even if the needle is changed. Patients using vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens

Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin strength, manufacturer, type, injection site, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Any changes in insulin regimen should be made cautiously under close medical supervision and the frequency of blood glucose monitoring should be increased. Due to reports of hyperglycemia and hypoglycemia, 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 blood glucose. For patients with type 2 diabetes, dosage adjustments of concomitant antidiabetic products may be needed.

Hypoglycemia: Severe hypoglycemia may be life threatening and can cause seizures or death. Hypoglycemia is the most common adverse reaction of Humalog and Insulin Lispro Injection. Monitor blood glucose and increase monitoring frequency with changes to insulin dosage, use with glucose-lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness.

Hypoglycemia Due to Medication Errors: Instruct patients to always check the insulin label before each injection to avoid medication errors. Humalog U-200 should not be transferred from the Humalog KwikPen to a syringe as overdose and severe hypoglycemia can occur.

Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with Humalog and Insulin Lispro Injection. If hypersensitivity reactions occur, discontinue the use of insulin and treat per standard of care until signs and symptoms resolve.

Hypokalemia: Hypokalemia may be life threatening. Insulins, including Humalog and Insulin Lispro Injection, cause a shift in potassium from the extracellular to intracellular space possibly leading to hypokalemia, which, if untreated, may result in respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia (e.g., patients using potassium-lowering medications or medications sensitive to serum potassium concentrations).

Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Thiazolidinediones (TZDs), which are PPAR-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin, including Humalog and Insulin Lispro Injection. This may lead to or exacerbate heart failure. Observe patients for signs and symptoms of heart failure and consider discontinuation or dose reduction of the PPAR-gamma agonist.

Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Malfunction of the insulin pump device, infusion set, or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Patients using subcutaneous insulin infusion pumps must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.

Adverse reactions associated with Humalog and Insulin Lispro Injection include hypoglycemia, hypokalemia, allergic reactions, injection-site reactions, lipodystrophy, pruritus, rash, weight gain, and peripheral edema.

Some medications may alter glucose metabolism, insulin requirements, and the risk for hypoglycemia or hyperglycemia. Signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs. Particularly close monitoring may be required.

HI BOI SP U100 75/25 HCP ISI 14SEP2022

INDICATIONS

Humalog and Insulin Lispro Injection are rapid-acting insulin analogs indicated to improve glycemic control in adults and children with diabetes mellitus. Humalog Mix75/25 and Humalog Mix50/50, and Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 are mixtures of intermediate-acting and rapid-acting insulin analogs indicated to improve glycemic control in patients with diabetes mellitus.

Limitations of Use: The proportions of rapid-acting and intermediate-acting insulins in Humalog Mix75/25 and Humalog Mix50/50, and Insulin Lispro Protamine and Insulin Lispro Injectable Suspension Mix75/25 are fixed and do not allow for basal versus prandial dose adjustments.

Consider Humalog for your patients with diabetes who:

Humalog U-100 reduced postprandial blood glucose compared to regular human insulin*1,2

Humalog U-100 provided improved glycemic control when used in an external insulin pump5

Humalog dosed 15 minutes before or immediately after meals when added to a basal insulin:

IMPORTANT SAFETY INFORMATION

INDICATIONS

Humalog U-100 reduced postprandial blood glucose compared to regular human insulin^*1,2

Humalog U-100 provided improved glycemic control when used in an external insulin pump⁵