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Dx Diabetes Mellitus- Insulin Treatment Overview:



There is a New Paradigm that changes the use of Insulin! Use Human Insulin- equal and much less expensive!
Tracy Tylee, M.D. and Ira B.Hirsch, M.D. at the University of Washington School of Medicine stated that there was no cost justification in using the newer insulins.

Kasa J. Lipska M.D., from Yale in JAMA 2017:318(91): 23-24 wrote in greater depth that Human insulin offers an almost 5-fold lower cost of insulin ($25) versus the lispro or aspart short-acting insulin analogues ($175/vial)with equal efficacy.

Differences Should be noted:

"Affordability of insulin has become a major issue for patients with diabetes in the United States1]. The price of insulin, particularly insulin analogues, has increased substantially over the past two decades.1] Pharmacy prices for 1 vial of glargine or detemir(long-acting insulin analogues) or 1 vial of lispro or aspart (short-acting insulin analogues) now exceeds $170 (Table). Prefilled pen injector are even ore expensive. Insurance may cover some of the cost, but the burden is increasingly shifting to patients in the form of higher premiums and co-payments. As a result, insulin analogues are not feasible for many uninsured or under-insured patients.

Synthetic human insulin, once the mainstay of treatment, is much less expensive but is now prescribed less frequently.[2] A vial of neutral protamine Hagedorn (NPH), human regular (R) insulin, premixed 70/30 NPH, or egular (Novolin R, N or 70/30) insulin can be obtained for as little as $25, approximately one-tenth of the list price of analogues. Although strategies for using human insulins were well understood 20 years ago, most raining programs longer emphasize the use of these agents. the advantages of insulin analogues over human insulins are less clear for type 2 diabetes than for type 1 diabetes. For patients with type 2 diabetes,insulin analogues do not improve glycemc control or reduce the risk of severe hypoglycemia compared with human insulin ut long-acting insulin analogues modestly reduce the risk of overall and nocturnal hypoglycemia.[3,4] In addition insulin does for type 2 diabetes and thus costs,are generally higher. When used skillfully, human N, human R, and premixed human insulin formulas can e very effective for glycemic control in type 2 diabetes.This Viewpoint provides recommendations for the use of human insulin in this setting.

How Treatment with Human Insulins Differs

Some differing properties of Human N Insulin and Human R Insulin, compare with those of insulin analogues, require modest but important differences in therapeutic approaches (Table).

Duration of Action. The action of human N insulin does not reliably cover 24 hours so more than 1 daily injection is often required (Table). In contrast, the long-acting analogues have relatively constant plasma insulin levels and duration of action approaching or beyond 24 hours at doses common in type 2 diabetes(20-60U/).[5]

Hypoglycemia Risk. Among patients with type 2 diabetes, long-acting insulin analogues modestly reduce the rate of nocturnal hypoglycemia compared with human N insulin.[4]. To limit the risk of hypoglycemia with human insulin, patient education, strategic snacking (eg., bedtime),self-measured plasma glucose targets, and when appropriate, less-aggressive hemoglobin A1c (HbA1c) targets may be advisable.

Timing with Meals. Human R insulin begins to action sooner than 30 minutes after injection, while rapid-acting insulin analogues (lispro, aspart, and glulisine) have a shorter onset of action of 5 to 15minutes. Based on these differences, human R insulin is typically injected 20 minutes before meals whereas insulin analogues are injected right before meals.While this is common practice, one trial suggests that human R insulin can be injected immediately before meals without appreciable differences in glycemic control or hypoglycemia [6].

Vial vs Pen
Insulin can be injected with a syringe (filled from a vial) or a pen. Prefilled pens are more convenient than syringes and may be more accurate when small doses of insulin are used or when patients have problems with dexterity or vision However, the least-expensive human insulin products (ReliOn) are not available as prefilled pens and no human R product is available in a pen in the United States.

Injection Technique. Human N insulin is a cloudy particulate suspension. To avoid inconsistent effects,it must be gently agitated before drawing into a syringe for injection. Absorption of human R insulin is fastest when injected from abdominal sites,followed by the upper arm and thigh; wehereas absorption kinetics of rapid-acing insulin analogues seem less site dependent.[7]

Starting Human Insulin. Patients must be involved in the decision to start insulin and in the selection of the type of insulin to be used. The patient's cognitive and physical capacity, motivation, daily routines 9includig the timing and consistency of meals), an preferences about treatment are critically important in choosing an insulin regime, whether human or analogue, that will fit each patient's individual context. Cost has to be considered(Table) because even the best plan cannot be realize if the patient cannot afford the treatment.

The purpose of bedtime basal insulin is to suppress overnight hepatic glucose production. The starting dose of bedtime human N insulin is typically 10U (or 0.2U/kg of body weight). The dose can be titrated up by 2 U every week (or 2x/wk if desired) until target fasting plasma glucose levels are acieved. When fasting target levels are achieved but glycemic control remains suboptimal at other times, advancing to a 2-injection regimen of human N insulin (at bedtime and before breakfast) can be considered. When a mealtime injection of human R insulin is added, 6 U injected into the abdomen is usually an appropriate starting dose.

Premixed 70/30 human insulin (70% N insulin with 30% R insulin) can be used as a 2-injection regimen, taken before breakfast and dinner. Although this regimen is simple,, it is limited by higher risk of hypoglycemia in miay and near midnight,the times of its peaks of action. For patients with HbA1c greater than 9% of total hemoglobin, this dose can be started(0.3U/kg per day) in approximately equal doses before breakfast and dinner. With this approach, patients can be typically attain HbA1c levels in the 7.'0%to 8.0% range before hypoglycemia limits further titration. The tendency to cause hypoglycemia ins the main drawback o this approach, but overall glycemicv control and risk of hypoglycemia do not greatly differ between human and analogue premixed insulins [8].

,font color"red">Switching to Human Insulin
Patents can safely switch from insulin analogues to human insulins. Total daily insulin dose can be initially reduced by 20%, because of the different profiles of action and because some patinets may have been taking less analogue insulin than had been prescibed.

For patients already treated with multiple insulin analogues injections, the number of injections and distribution of dosage ca remain the same but with a 20% reduction of dosage for safety. Early contact between the physician and the patient by phone or in person is desirable to ensure that an unexpectedly large reduction of glucose as not occurred due to improve adherence.

In summary many patients with type 2 diabetes can be treated with human insulin. due to high costs of analogue insulin, use of human insulin may be the only practical option for some patients,and clinicians should be familiar with its use.

TABLE: Characteristics of Selected Synthetic Human Insulin and Analogue Insulin Products

Characteristics of Selected Synthetic Human Insulin and Analogue Insulin Products

Synthetic Human
Onset Peak
Time of Action
Duration Use trade Name US
per vial
per carton
_____________________________________________________________________________________________________________________ ______
NPH (N) 2-4 hourshuman
4-10 h
12- 18 h Once at bedtime or twice daily Novolin N
Humulin N

Regular (r)30-60 min2-3 h   8 - 10 h 0-30 min before meals Novulin R
Humulin R

Premixed 70/30 N/R 1/2 to 1 hour 2-6 h  12 - 18 h Before breakfast and dinner Novolin 70/30
Humulin 70/30
Insulin Analogues
Degludec 1 hourNo peak>40 h Once daily TresibaNA390-452

Detemir3- 4 h 3-9 h  6 - 24 h Once or twice daily Levemir221-284 330-409
Glargine 2 - 6 h No Peak   20 - 24 h Once or twice daily Lantus

Aspart 5 - 15 min 30 - 90 min  4 - 6 h 0 - 15 min before meals Novolog 210- 290 403 - 538
Glulisine 5 - 15 min 30 - 90 min  4 - 6 h 0 - 15 min before meals Aprida185 400
Lispro 5 - 15 min 30 - 90min  4 - 6 h 0- 15 min before meals Humalog174 322
Premixed 5 - 15 min 2-4 h  14 - 24 h 0 - 15 min before meals Novolog 70/30
Humalog 70/30
Humalog 50/50
218 - 300

Medical Article
Effect of Insulin Degluec vs insulin Glargine U1000 on Hypoglycemia in Patients with Type I Diabetes. The Switch 1 Randomized Clinical Trial. JAMA 2017;318910:33-44

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