Type 2 diabetes Humalog® improved glycemic control

When added to a basal insulin in patients with type 2 diabetes, Humalog dosed 15 minutes before or immediately after meals:

  • Reduced postprandial glucose (PPG) levels1
  • Lowered A1C2

Why postprandial glucose matters3

The overall measurement of glycemic control (A1C) reflects a combination of both fasting plasma glucose (FPG) and postprandial glucose (PPG).3 Ninety-nine percent of patients with A1C values greater than or equal to 7% have 2-hour PPG greater than or equal to 200 mg/dL.4 As your patient’s A1C levels approach the normal range, PPG contributes more to the A1C than FPG.3 Therefore, management of postprandial hyperglycemia is important for achieving recommended A1C goals.

As A1C levels approach the normal range, PPG contributes more to the A1C than FPG3

A1C levels
  • PPG=postprandial plasma glucose
  • FPG=fasting plasma glucose

The relative contribution of fasting and postprandial blood glucose varies with A1C.

Humalog U-100 compared to regular human insulin

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

53%*4

*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.

Humalog U-200 is bioequivalent to Humalog U-1001

It provides the same rapid onset and same duration of action. Bioequivalency was determined by area under the curve and maximum concentration.

Learn more about Humalog U-200 efficacy Learn about efficacy with the Humalog U-100 self-titration algorithm

Select Safety Information

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with Humalog, Humalog Mix75/25, and Humalog Mix50/50. If hypersensitivity reactions occur, discontinue the insulin and treat per standard of care until signs and symptoms resolve.

Efficacy of Humalog® Mix75/25 (75% insulin lispro protamine suspension and 25% insulin lispro injection [rDNA origin])

Humalog Mix75/25 provided improved glucose control

Two studies in adult patients with type 2 diabetes

When added to metformin, Humalog Mix75/25 improved A1C (PAIR-IN: Glycemic control5)

  • Two open-label, randomized crossover trials compared the glycemic response of Humalog Mix75/25 BID + metformin with that of glargine QD + metformin5,6

Humalog Mix75/25 improved fasting plasma glucose (FPG) and postprandial glucose (PPG) control

  • A randomized, double-blind study with 3-way crossover compared Human Insulin 70/30, Humalog Mix75/25, and Humalog® Mix50/50 after a standardized breakfast meal7

Select Safety Information

Humalog differs from regular human insulin by its rapid onset of action as well as a shorter duration of activity. Therefore, the dose of Humalog Mix75/25 should be given within 15 minutes before a meal.

PAIR-IN: Design and methods

  • Humalog Mix75/25 BID plus metformin versus glargine QD plus metformin
  • Open-label, randomized, crossover trial, 16 weeks on each treatment
  • 105 insulin-naive patients with type 2 diabetes
  • Mean age 55 years
    • All randomized patients included in safety analysis
    • 67 patients included in efficacy analysis (29 patients excluded because they may have received expired study drug)
  • Baseline A1C: 8.7%

Primary endpoint

  • Change in A1C over 16 weeks

Note: PAIR-IN average (standard deviation) daily dose of insulin was 0.62 (0.37) U/kg for Humalog Mix75/25 vs 0.57 (0.37) U/kg glargine (P<.001).

PAIR-IN: A1C change from baseline5

Pair-In: A1C change from baseline

PAIR-IN: Percent of patients to A1C goal of <7%5

PAIR-IN: Percent of patients to A1C goal of <7%

PAIR-IN: FBG control5

PAIR-IN: FBG control

PAIR-IN: Hypoglycemia5

Overall hypoglycemia rates for the groups were as follows:

  • Humalog Mix75/25 + MET group: 0.68 episodes/patient per 30 days
  • Glargine + MET group: 0.39 episodes/patient per 30 days

Nocturnal hypoglycemia rates for the groups were as follows:

  • Humalog Mix75/25 + MET group: 0.14 episodes/patient per 30 days
  • Glargine + MET group: 0.24 episodes/patient per 30 days

PAIR-IN: Overall hypoglycemia

PAIR-IN: Overall hypoglycemia

PAIR-IN: Nocturnal hypoglycemia

PAIR-IN: Nocturnal hypoglycemia

PAIR-IN

  • Humalog Mix75/25 BID plus metformin versus glargine QD plus metformin
  • Insulin-naive patients with type 2 diabetes
  • 105 patients
  • 67 patients included in efficacy analysis (29 patients excluded, since they may have received expired study drug)
  • Baseline A1C: 8.7%

NOTE: PAIR-IN average (standard deviation) daily dose of insulin was 0.62 (0.37) U/kg for Humalog Mix75/25 vs 0.57 (0.37) U/kg for glargine (P<.001).

PAIR-PI: Design and methods

  • Humalog Mix75/25 BID plus metformin versus glargine QD plus metformin
  • Inadequately controlled patients with type 2 diabetes on once- or twice-daily insulin alone or in combination with oral agents
  • 97 patients
  • Open-label, randomized crossover trial

Note: PAIR-PI average (standard deviation) daily dose of insulin was 0.42 (0.20) U/kg for Humalog Mix75/25 vs 0.36 (0.18) U/kg glargine (P<.001).

PAIR-PI: A1C change from baseline6

PAIR-PI: A1C change from baseline

PAIR-PI: Percent of patients to A1C goal of <7%6

PAIR-PI: Percent of patients to A1C goal of <7%

PAIR-PI: FBG control6

PAIR-PI: FBG control

PAIR-PI: Hypoglycemia6

Overall hypoglycemia rates for the groups were as follows:

  • Humalog Mix75/25 + MET group: 0.61 episodes/patient per 30 days
  • Glargine + MET group: 0.44 episodes/patient per 30 days

Nocturnal hypoglycemia rates for the groups were as follows:

  • Humalog Mix75/25 + MET group: 0.14 episodes/patient per 30 days
  • Glargine + MET group: 0.34 episodes/patient per 30 days

PAIR-PI: Overall hypoglycemia

PAIR-PI: Overall hypoglycemia

PAIR-PI: Nocturnal hypoglycemia

PAIR-PI: Nocturnal hypoglycemia

PAIR-PI

  • Humalog Mix75/25 BID plus metformin versus glargine QD plus metformin
  • Inadequately controlled patients with type 2 diabetes on once- or twice-daily insulin alone or in combination with oral agents
  • 97 patients
  • Open-label, randomized crossover trial

NOTE: PAIR-PI average (standard deviation) daily dose of insulin was 0.42 (0.2) U/kg for Humalog Mix75/25 vs 0.36 (0.18) U/kg for glargine (P<.001).

Select Safety Information

Hypokalemia may be life threatening. Insulins, including Humalog, Humalog Mix75/25 and Humalog Mix50/50, 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 (eg, patients using potassium-lowering medications or medications sensitive to serum potassium concentrations).

Severe hypoglycemia may be life threatening and can cause seizures or death. Hypoglycemia is the most common adverse effect of Humalog, Humalog Mix75/25, and Humalog Mix50/50 therapy. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia.

Humalog Mix75/25 improved fasting and postprandial glucose control7

Design and methods

  • Comparison of insulin formulations: Human Insulin 70/30, Humalog Mix75/25, and Humalog Mix50/50 after a standardized breakfast meal
  • Study was randomized and double-blind, with 3-way crossover of the premixed insulins in patients with type 2 diabetes. A control group of subjects without diabetes underwent the standardized test meal with no insulin treatment
  • After the test breakfast, glucose was measured for 4 hours
  • 22 patients received a single dose of Human Insulin 70/30 before breakfast; 22 received Humalog Mix75/25; and 23 received Humalog Mix50/50. Ten subjects without diabetes received no insulin. One patient who received Human Insulin 70/30 before the test meal, followed by the usual dose of insulin lispro before lunch, reported symptoms of hypoglycemia that resolved with oral carbohydrate

Pre- and postprandial serum glucose concentrations

Pre- and postprandrial serum glucose concentrations

Note: Mean (SD) dose of insulin was 44.1 (18.2) U/day for Human Insulin 70/30; 44.1 (18.2) U/day for Humalog Mix75/25; and 43.8 (17.8) U/day for Humalog Mix50/50. Standard test breakfast: 500 kcal; 50% carbohydrate, 34% fat, 16% protein. Each regimen resulted in 2-hour postprandial glucose significantly different from all other regimens (pairwise comparison).

Efficacy of Humalog® Mix50/50 (50% insulin lispro protamine suspension and 50% insulin lispro injection [rDNA origin])

Humalog Mix50/50 improved postprandial glucose control7-9

A randomized, double-blind study compared Human Insulin 70/30, Humalog Mix75/25, and Humalog Mix50/50 after a standardized breakfast meal in patients with type 2 diabetes.7 Humalog Mix50/50 improved postprandial glucose control.7-9

Design and methods7

  • Comparison of insulin formulations: Human Insulin 70/30, Humalog Mix75/25, and Humalog Mix50/50 after a standardized breakfast meal
  • Study was randomized and double-blind, with 3-way crossover of the premixed insulins in patients with type 2 diabetes. A control group of subjects without diabetes underwent the standardized test meal with no insulin treatment
  • All patients previously used insulin (excluding insulin glargine) for at least one month prior to the study
  • After the test breakfast, glucose was measured for 4 hours
  • 22 patients received a single dose of Human Insulin 70/30 before breakfast; 22 received Humalog Mix75/25; and 23 received Humalog Mix50/50. Ten subjects without diabetes received no insulin. One patient who received Human Insulin 70/30 before the test meal, followed by the usual dose of insulin lispro before lunch, reported symptoms of hypoglycemia that resolved with oral carbohydrate

Humalog Mix50/50 provided improved postprandial control for patients after a standardized breakfast meal7

Humalog Mix50/50 provided improved postprandrial control for patients after a standardized breakfast meal

*Each regimen resulted in 2-hour postprandial glucose significantly different from all other regimens (pairwise comparison).

Note: Mean (SD) dose of insulin was 44.1 (18.2) U/day for Human Insulin 70/30; 44.1 (18.2) U/day for Humalog Mix75/25; and 43.8 (17.8) U/day for Humalog Mix50/50. Standard test breakfast: 500 kcal; 50% carbohydrate, 34% fat, 16% protein.

Humalog Mix50/50 dosing guidelines

Select Safety Information

Fluid retention and heart failure can occur with concomitant use of TZDs and Humalog, Humalog Mix 75/25, and Humalog Mix 50/50. Observe patients for signs and symptoms of heart failure and consider discontinuation to dose reduction of the PPAR-gamma agonist.

Hypoglycemia is the most common adverse effect associated with Humalog Mix50/50. Severe hypoglycemia can cause seizures and may be life threatening. The timing of hypoglycemia may differ among various insulin formulations.

Type 1 diabetesHumalog offers improved glycemic control2

In patients with type 1 diabetes, Humalog U-100:

  • Reduced postprandial glucose (PPG) levels when added to basal insulin10
  • Reduced PPG to a greater extent compared to regular insulin in pediatric patients; A1C did not differ between patients treated with regular insulin and those treated with Humalog11,12
  • Provided rapid,2,13-16 effective,2,13-16 and stable2,14,16 control of blood glucose in adult13-15 and pediatric2,16 patients using an insulin pump

Select Safety Information

Humalog U-100 should not be diluted or mixed when used in an external insulin pump. Change Humalog U-100 in the reservoir at least every 7 days. Change the infusion set and insertion site at least every 3 days. Do not use Humalog Mix75/25, Humalog Mix50/50, or Humalog U-200 in an external insulin pump.

Why postprandial glucose matters3

The overall measurement of glycemic control (A1C) reflects a combination of both fasting plasma glucose (FPG) and postprandial glucose (PPG).3 Ninety-nine percent of patients with A1C values greater than or equal to 7% have 2-hour PPG greater than or equal to 200 mg/dL.4 As your patient’s A1C levels approach the normal range, PPG contributes more to the A1C than FPG.3 Therefore, management of postprandial hyperglycemia is important for achieving recommended A1C goals.

As A1C levels approach the normal range, PPG contributes more to the A1C than FPG3

As A1C levels approach the normal range, PPG contributes more to the A1C that FPG
  • PPG=postprandial plasma glucose
  • FPG=fasting plasma glucose

The relative contribution of fasting and postprandial blood glucose varies with A1C.

Humalog U-100 reduced postprandial blood glucose compared to regular human insulin

In pediatric patients with type 1 diabetes, 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.11,12

Study design11

  • 61 children (2.9 to 11.4 years), mean baseline A1C value 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
      • Humalog immediately postmeal
      • Humalog 15 minutes premeal
      • 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

Select Safety Information

Humalog should be given within 15 minutes before or immediately after a meal.

Humalog U-100 provided glycemic control when used in an external insulin pump2,10-13

Humalog provided rapid,2,13-16 effective,2,13-16 and stable2,14,16 control of blood glucose in adult13-15 and pediatric2,16 patients with type 1 diabetes using an insulin pump in clinical trials. 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 provided rapid, effective, and stable control of blood glucose levels in patients using insulin pumps when compared with regular human insulin.13 The use of Humalog significantly reduced A1C and postprandial glucose levels, without increasing hypoglycemic episodes.13

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 in A1C and comparable rates of hypoglycemia as insulin aspart.16

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

Humalog U-100 should not be diluted or mixed when used in an external insulin pump. Change Humalog U-100 in the reservoir at least every 7 days. Change the infusion set and insertion site at least every 3 days. Do not use Humalog Mix75/25, Humalog Mix50/50, or Humalog U-200 in an external pump.

Insulin pump or infusion set malfunction or degradation of the insulin in the pump reservoir can rapidly result in hyperglycemia and ketoacidosis. Patients should be instructed to carry alternate insulin therapy in case of pump failure.

Humalog U-100 in an external insulin pump is approved for use in patients with type 1 diabetes 4 years of age and older.

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%).

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. Humalog [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015.
  3. American Diabetes Association. Standards of Medical Care in Diabetes—2014. Diabetes Care. 2014;37(suppl 1):S14-S80.
  4. 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.
  5. Malone JK, Kerr LF, Campaigne BN, et al. Lispro Mixture-Glargine Study Group. Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy [published correction appears in Clin Ther. 2005;27(7):1112]. Clin Ther. 2004;26(12):2034-2044.
  6. Malone JK, Bai S, Campaigne BN, et al. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with type 2 diabetes. Diabet Med. 2005;22(4):374-381.
  7. Schwartz S, Zagar AJ, Althouse SK, et al. A single-center, randomized, double-blind, three-way crossover study examining postchallenge glucose responses to human insulin 70/30 and insulin lispro fixed mixtures 75/25 and 50/50 in patients with type 2 diabetes mellitus. Clin Ther. 2006;28(10):1649-1657.
  8. Kazda C, Hülstrunk H, Helsberg K, Langer F, Forst T, Hanefeld M. Prandial insulin substitution with insulin lispro or insulin lispro mid mixture vs basal therapy with insulin glargine: a randomized controlled trial in patients with type 2 diabetes beginning insulin therapy. J Diabetes Complications. 2006;23:145-152.
  9. Roach P, Trautmann M, Arora V, Sun B, Anderson JH Jr. Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Clinical Ther. 1999;23:523-534.
  10. 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.
  11. Deeb LD, Holcombe JH, Brunelle R, et al. Insulin lispro lowers postprandial glucose in prepubertal children with diabetes. Pediatrics. 2001;108:1175-1179.
  12. 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.
  13. 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.
  14. Zinman B, Tildesley H, Chiasson JL, et al. Insulin lispro in CSII: results of a double-blind crossover study [published correction appears in Diabetes. 1997;46(7):1239]. Diabetes. 1997;46(3):440-443.
  15. 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):78.
  16. 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.