Insulin

(rINN)
Insulin Chemical formula

Chemical information

Insuliini; Insülin; Insulina; Insuline; Insulinin; Insulinum.
CAS — 9004-10-8 (insulin; neutral insulin); 11070-73-8 0 (human insulin); 8063-29-4 (biphasic insulin); 9004-211 (globin zinc insulin); 68859-20-1 (insulin argine); 804962-5 (insulin zinc suspensions); 53027-39-7 (isophane insulin); 9004-17-5 (protamine zinc insulin); 116094-23-6 72-2 (bovine insulin defalan); 11091-62-6 (porcine insulin defalan); 160337-95-1 (insulin glargine); 133107-64-9 ATC — A10AB01 (human); A10AB02 (beef); A10AB03 ATC Vet — QA10AB01 (human); QA10AB02 (beef); QA10AB03 (pork); QA10AB04 (lispro); QA10AB05 (aspart); QA10AB06 (glulisine); QA10AC01 (human); QA10AC02 (beef); QA10AC03 (pork); QA10AC04 (lispro); QA10AD01 (human); QA10AD02 (beef); QA10AD03 QA10AE01 (human); QA10AE02 (beef); QA10AE03 QA10AF01 (human).

Pharmacopoeias.

Most pharmacopoeias have monographs for insulin and a variety of insulin preparations.

Ph. Eur. 6.2 (Insulin, Bovine). The natural antidiabetic principle obtained from beef pancreas and purified. A white or almost white powder. Practically insoluble in water and in dehydrated alcohol. It dissolves in dilute mineral acids and, with decomposition, in dilute solutions of alkali hydroxides. Store in airtight containers. Protect from light. It should be stored at −20° until released by the manufacturer. When thawed, insulin may be stored at 2° to 8° and used for manufacturing purposes within a short period of time. To avoid absorption of humidity from the air during weighing, the insulin must be at room temperature.

Ph. Eur. 6.2 (Insulin, Porcine). The natural antidiabetic principle obtained from pork pancreas and purified. A white or almost white powder. Practically insoluble in water and in dehydrated alcohol. It dissolves in dilute mineral acids and, with decomposition, in dilute solutions of alkali hydroxides. Store in airtight containers. Protect from light. It should be stored at −20° until released by the manufacturer. When thawed, insulin may be stored at 2° to 8° and used for manufacturing purposes within a short period of time. To avoid absorption of humidity from the air during weighing, the insulin must be at room temperature.

Ph. Eur. 6.2 (Insulin, Human). A protein having the structure of the antidiabetic hormone produced by the human pancreas. It is produced either by enzymatic modification and suitable purification of insulin obtained from the pancreas of the pig or by a method based on recombinant DNA (rDNA) technology. A white or almost white powder. Practically insoluble in water and in alcohol. It dissolves in dilute mineral acids and, with decomposition, in dilute solutions of alkali hydroxides. Store in airtight containers. Protect from light. It should be stored at or below −18° or below until released by the manufacturer. When thawed, insulin is stored at 2° to 8° and used for manufacturing preparations within a short period of time. To avoid absorption of humidity from the air during weighing, the insulin must be at room temperature.

Ph. Eur. 6.2 (Insulin DIABETIC EMERGENCIES. Potassium, and possibly phosphate, replacement may also be required, but bicarbonate should not be given unless acidaemia is very severe. In the UK the BNF recommends that insulin be given by intravenous infusion for diabetic ketoacidosis, as a solution of soluble insulin 1 unit/mL via an infusion pump. An infusion rate of 6 units/hour in adults and 0.1 units/kg per hour in children is recommended initially, with the rate doubled or quadrupled if the blood glucose concentration fails to decrease by about 5 mmol/litre per hour. When blood glucose concentrations have fallen to 10 mmol/litre the infusion rate can be reduced to 3 units/hour in adults or about 0.05 units/kg per hour in children, and continued, with glucose 5% to prevent hypogly caemia, until the patient is ready to take food by mouth. The insulin infusion should not be stopped before subcutaneous insulin has been started. Potassium chloride is included in the infusion as appropriate to prevent insulin-induced hypokalaemia. If facilities for intravenous infusion are not available the insulin is given by intramuscular injection: in adults an initial loading dose of 20 units intramuscularly is followed by 6 units intramuscularly every hour until the blood glucose concentration falls to 10 mmol/litre, when the dose is given every 2 hours. Late hypoglycaemia due to insulin accumulation should be watched for and managed appropriately. In the USA the intramuscular or the subcutaneous route have been used as alternatives to intravenous insulin, with other appropriate management. One successful set of protocols for insulin dosage in diabetic ketoacidosis is as follows:1 an initial intravenous bolus of 0.15 units/kg is followed by infusion of 0.1 units/kg per hour; if blood glucose does not fall by about 2.5 to 3.5 mmol/litre in the first hour the infusion rate is doubled every hour until this rate of decline is achieved. (A similar insulin regimen has proved effective in patients with hyperosmolar hyperglycaemic state.1) When given by the intramuscular or subcutaneous routes an initial bolus of 0.4 units/kg is divided and given half by the intravenous route and half either intramuscularly or subcutaneously as appropriate. This is followed by 0.1 units/kg every hour intramuscularly or subcutaneously; if response is inadequate it is replaced by an intravenous bolus of 10 units until blood glucose falls by 2.5 to 3.5 mmol/litre. In children intravenous infusion of 0.1 units/kg per hour is recommended, or if intravenous infusion is impractical an initial intramuscular bolus of 0.1 units/kg followed by 0.1 units/kg per hour either intramuscularly or subcutaneously. Treatment is continued at this rate until a serum-glucose concentration of about 12.5 mmol/litre is reached (or about 15 mmol/litre for hyperosmolar hyperglycaemic state), when the rate is decreased to 0.05 to 0.1 units/kg per hour until acidosis is controlled and subcutaneous insulin replacement treatment can be started.
1. American Diabetes Association. Hyperglycemic crises in diabetes. Diabetes Care 2004; 27 (suppl 1): S94–S102. Also available at: http://care.diabetesjournals.org/cgi/reprint/27/suppl_1/ s94.pdf (accessed 26/05/04)
TYPE 2 DIABETES MELLITUS. Traditionally the use of insulin in patients with type 2 diabetes has tended to be reserved for those who cannot be controlled by diet and oral antidiabetics alone.1,2 Given the possible association between circulating insulin and atherosclerotic cardiovascular symptoms3 there has been some concern about the use of exogenous insulin in insulin-resistant patients who are already hyperinsulinaemic. Furthermore, patients switched to insulin tend to gain weight2which is undesirable in a frequently obese patient group. Insulin is nonetheless being used more frequently in type 2 patients. This is largely because of a trend toward more intensive regimens designed to produce tighter glycaemic control, on the hypothesis that, as in patients with type 1 disease, this will reduce the development and progression of diabetic complications. Results from the UK Prospective Diabetes Study,4-6 show that insulin is an effective option in type 2 diabetes, and confirm both the value of intensive therapy in retarding microvascular complications,6 and that oral therapy should be used before insulin in patients with primary diet failure.7 In order to minimise the dose of insulin required, and any risks it may entail, it has been suggested that insulin therapy in type 2 diabetes should be combined with other measures including oral hypoglycaemic drugs.8 There has long been debate about the value of combined therapy, but a meta-analysis indicated that glycaemic control was better, and insulin requirements lower, in type 2 diabetics who received insulin with a sulfonylurea.9 For evidence that the insulin analogues insulin lispro and insulin aspart have no advantage over regular insulin in type 2 patients see Insulin Analogues, above. For further discussion of the management of type 2 diabetes mellitus.
1. Tattersall RB, Scott AR. When to use insulin in the maturity onset diabetic. Postgrad Med J 1987; 63: 859–64
2. Taylor R. Insulin for the non-insulin dependent? BMJ 1988; 296: 1015–16
3. Stern MP. Do non-insulin-dependent diabetes mellitus and cardiovascular disease share common antecedents? Ann Intern Med 1996; 124 (suppl): 110–16
4. United Kingdom Prospective Diabetes Study Group. United Kingdom prospective diabetes study (UKPDS) 13: relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin-dependent diabetes followed for three years. BMJ 1995; 310: 83–8
5. Turner R, et al. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med 1996; 124 (suppl): 136–45
6. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–53. Correction. ibid. 1999; 354: 602
7. United Kingdom Prospective Diabetes Study Group. United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med 1998; 128: 165–75
8. Henry RR. Glucose control and insulin resistance in non-insulindependent diabetes mellitus. Ann Intern Med 1996; 124 (suppl): 97–103
9. Johnson JL, et al. Efficacy of insulin and sulfonylurea combination therapy in type II diabetes: a meta-analysis of the randomized placebo-controlled trials. Arch Intern Med 1996; 156: 259–64.

Diagnosis and testing.

PITUITARY FUNCTION. Insulininduced hypoglycaemia has been used to provide a stressful stimulus in order to assess hypothalamic-pituitary function. The insulin stress or insulin-tolerance test has been used as a standard test for assessment of growth hormone or corticotropin deficiency. However, it is unpleasant, expensive, and not without risk, and is contra-indicated in patients with angina, heart failure, cerebrovascular disease, or epilepsy; some recommend its use only when results of alternative tests are equivocal,1-3 and it should only be performed in specialist units under strict surveillance.4
1. Clayton RN. Diagnosis of adrenal insufficiency. BMJ 1989; 298: 271–2
2. Stewart PM, et al. A rational approach for assessing the hypothalamic-pituitary-adrenal axis. Lancet 1988; 1: 1208–10
3. Lindholm J. The insulin hypoglycaemia test for the assessment of the hypothalamic–pituitary–adrenal function. Clin Endocrinol (Oxf) 2001; 54: 283–6
4. Hindmarsh PC, Swift PGF. An assessment of growth hormone provocation tests. Arch Dis Child 1995; 72: 362–8.

Hyperkalaemia.

Insulin promotes the intracellular uptake of potassium. It is therefore used in the management of moderate to severe hyperkalaemia, when it is given with glucose.

Liver disorders.

There have been reports1,2 of benefit from the use of insulin and glucagon in the treatment of liver disorders, based on their reported hepatotrophic effect. However, randomised studies have found no benefit from insulin and glucagon infusions in fulminant hepatic failure3 and acute alcoholic hepatitis.4
1. Baker AL, et al. A randomized clinical trial of insulin and glucagon infusion for treatment of alcoholic hepatitis: progress report in 50 patients. Gastroenterology 1981; 80: 1410–14
2. Jaspan JB, et al. Insulin and glucagon infusion in the treatment of liver failure. Arch Intern Med 1984; 144: 2075–8
3. Harrison PM, et al. Failure of insulin and glucagon infusion to stimulate liver regeneration in fulminant hepatic failure. J Hepatol 1990; 10: 332–6
4. Bird G, et al. Insulin and glucagon infusion in acute alcoholic hepatitis: a prospective randomized controlled trial. Hepatology 1991; 14: 1097–1101.

Myocardial infarction.

Discussions on the effects of insulin with glucose and potassium in the ischaemic heart, including its effect in reducing blood free fatty acids, have emphasised its potential benefits in left ventricular failure and cardiogenic shock.1,2 A meta-analysis3 of randomised controlled studies performed before the widespread use of thrombolytics found a reduction in mortality in recipients of glucose-insulin-potassium solutions. However, although a pilot study4 that included patients undergoing reperfusion (thrombolysis or percutaneous coronary intervention) reported benefit, this was not confirmed in larger randomised studies using standard glucose-insulin-potassium infusions.5,6 A further study7 found that routine use of such infusions in patients undergoing reperfusion had no effect on myocardial salvage, although some improvement was reported in diabetics. Intensive glucose control, with insulin-glucose infusion followed by multiple daily subcutaneous insulin injections has been reported to reduce mortality in diabetics who suffered a myocardial infarction.8,9 A similar study10 of treatment after myocardial infarction included only patients with type 2 diabetes mellitus who were treated with routine care, or insulin-glucose infusion followed by either long-term subcutaneous insulin or standard glucose control. The study was stopped early due to slow patient recruitment, but results did suggest that although glucose concentration was a strong independent predictor of long-term mortality, the use of long-term insulin treatment did not improve survival compared with conventional treatment at similar levels of glucose control. An observational study11 in non-diabetics with hyperglycaemia suggested that intensive glucose control also improved outcomes in this population, but another study12 found no benefit. However, the glucose control achieved in this study was similar in both the intensive and the conventional treatment groups and an analysis based on blood glucose concentrations suggested that strict glucose control was beneficial.12 For the conventional management of myocardial infarction.
1. Opie LH. Glucose and the metabolism of ischaemic myocardium. Lancet 1995; 345: 1520–1
2. Taegtmeyer H, et al. Metabolic support for the postischaemic heart. Lancet 1995; 345: 1552–5
3. Fath-Ordoubadi F, Beatt KJ. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation 1997; 96: 1152–6
4. Díaz R, et al. Metabolic modulation of acute myocardial infarction: the ECLA Glucose-Insulin-Potassium Pilot Trial. Circulation 1998; 98: 2227–34
5. Mehta SR, et al. Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial. JAMA 2005; 293: 437–46
6. Díaz R, et al. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA 2007; 298: 2399–2405
7. Pache J, et al. A randomized evaluation of the effects of glucose-insulin-potassium infusion on myocardial salvage in patients with acute myocardial infarction treated with reperfusion therapy. Am Heart J 2004; 148: e3
8. Malmberg K, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI Study): effects on mortality at 1 year. J Am Coll Cardiol 1995; 26: 57–65
9. Malmberg K, et al. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ 1997; 314: 1512–15
10. Malmberg K, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005; 26: 650–61
11. Weston C, et al. Early impact of insulin treatment on mortality for hyperglycaemic patients without known diabetes who present with an acute coronary syndrome. Heart 2007; 93: 1542–6
12. Cheung NW, et al. The Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) study: a randomized controlled trial of insulin infusion therapy for myocardial infarction. Diabetes Care 2006; 29: 765–70.

Neonatal hyperglycaemia.

Hyperglycaemia is common in very immature neonates because of delayed or reduced insulin production. It can be treated by glucose restriction until glucose tolerance improves. However, this may not provide enough glucose to meet basal metabolic needs, and the use of an insulin infusion can allow sufficient glucose to be given. It has been suggested that insulin is best given intravenously in a separate, easily titratable solution because of the frequent fluctuations of requirement in these infants.1
1. Ditzenberger GR, et al. Continuous insulin intravenous infusion therapy for VLBW infants. J Perinat Neonatal Nurs 1999; 13: 70–82.

Overdosage with calcium-channel blockers.

High-dose insulin, with glucose and potassium as required to maintain normal plasma concentrations of these, has been reported to be of value in the treatment of overdosage with calcium-channel blockers that has not been adequately managed with conventional therapy. A review1 of 13 reported cases found that various dosage regimens had been tried. These included bolus doses of insulin 10 to 20 units, and continuous infusions of 0.1 to 1 unit/kg per hour. The authors of one report2 have proposed a regimen that includes an initial intravenous bolus dose of insulin 1 unit/kg, followed by a continuous infusion of 0.5 units/kg per hour; this may be increased to 1 unit/kg per hour if necessary.
1. Shepherd G, Klein-Schwartz W. High-dose insulin therapy for calcium-channel blocker overdose. Ann Pharmacother 2005; 39: 923–30
2. Boyer EW, et al. Hyperinsulinemia/euglycemia therapy for calcium channel blocker poisoning. Pediatr Emerg Care 2002; 18: 36–7.

Preparations

BP 2008: Insulin Aspart Injection; Insulin Lispro Injection; Protamine Zinc Insulin Injection; Ph. Eur.: Biphasic Insulin Injection; Biphasic Isophane Insulin Injection; Insulin Zinc Injectable Suspension; Insulin Zinc Injectable Suspension (Amorphous); Insulin Zinc Injectable Suspension (Crystalline); Isophane Insulin Injection; Soluble Insulin Injection; USP 31: Extended Insulin Human Zinc Suspension; Extended Insulin Zinc Suspension; Human Insulin Isophane Suspension and Human Insulin Injection; Insulin Human Injection; Insulin Human Zinc Suspension; Insulin Injection; Insulin Lispro Injection; Insulin Zinc Suspension; Isophane Insulin Human Suspension; Isophane Insulin Suspension; Prompt Insulin Zinc Suspension.

Proprietary Preparations

Arg.: Actrapid HM; Actrapid MC†; Apidra; Biohulin C; Biohulin N; Densulin; Humalog; Humalog Mix 25; Humulin 70/30; Humulin L†; Humulin NPH; Humulin R; Humulin U†; Insulatard HM; Insulatard MC†; Insuman N; Insuman R; Lantus; Levemir; Mixtard 30 HM; Monotard HM†; Monotard MC†; NovoMix 30; NovoRapid; Austral.: Actrapid; Apidra; Humalog; Humalog Mix 25; Humulin 30/70; Humulin L†; Humulin NPH; Humulin R; Humulin UL†; Hypurin Isophane; Hypurin Neutral; Lantus; Levemir; Mixtard 20/80, 30/70, 50/50; Monotard†; NovoMix 30; NovoRapid; Protaphane; Ultratard†; Austria: Actrapid HM; Humalog; Humalog Mix 25 and 50; Huminsulin Basal; Huminsulin Long; Huminsulin Normal; Huminsulin Profil II and III; Huminsulin Ultralong; Insulatard HM; Insuman Basal; Insuman Comb 15, 25, and 50; Insuman Infusat; Insuman Rapid; Mixtard HM 10/90, 20/80, 30/70, 40/60, and 50/50; Monotard HM; Ultratard HM; Belg.: Actrapid HM; Humaject 30/70†; Humaject NPH†; Humaject Regular†; Humalog; Humalog Mix 25 and 50; Humuline 30/70, 50/50; Humuline Long†; Humuline NPH; Humuline Regular; Humuline Ultralong†; Insulatard; Lantus; Levemir; Mixtard 10, 20, 30, 40, 50; Monotard HM†; NovoMix 30; NovoRapid; Ultratard†; Velosulin; Braz.: Actrapid MC†; Biohulin 70/30, 80/20, and 90/10†; Biohulin Lenta†; Biohulin NPH; Biohulin Regular; Biohulin Ultralenta†; Exubera; Humalog; Humalog Mix 25; Humulin 70/30; Humulin Lenta; Humulin NPH; Humulin Regular; Insuman Comb 85N/15R and 75N/25R; Insuman N; Insuman R; Lantus; Levemir; Monotard MC†; Novolin 70/30; Novolin L†; Novolin N; Novolin R; Novolin U†; NovoRapid; Protaphane MC†; Canad.: Humalog; Humalog Mix 25; Humulin 20/80, 30/70; Humulin L; Humulin N; Humulin R; Humulin U; Hypurin NPH; Hypurin Regular; Iletin II Pork Lente; Iletin II Pork NPH; Iletin II Pork Regular; Lantus; Novolin 10/90, 20/80, 30/70, 40/60, 50/50; Novolin Lente†; Novolin NPH; Novolin Toronto; Novolin Ultralente†; NovoRapid; Chile: Actrapid HM; Actrapid†; Humalog; Humalog Mix 25; Humulin 70/30†; Humulin L†; Humulin N†; Humulin R†; Insulatard HM; Insulatard†; Insuman N; Insuman R; Lantus; Lenta†; Mixtard 30 HM; Monotard HM†; NovoMix 30; NovoRapid; Wosulin 30/70; Wosulin-N; Wosulin-R; Cz.: Actraphane; Actrapid; Exubera; Humalog; Humalog Mix 25 and 50; Humalog NPL; Humulin L†; Humulin M3; Humulin N; Humulin R; Humulin U†; Hypurin Bovine Isophane†; Hypurin Bovine Protamin Zink Sulfat†; Hypurin Porcin Neutral†; Insulatard; Insuman Basal; Insuman Comb 15, 25, and 50; Insuman Infusat; Insuman Rapid; Lantus; Levemir; Liprolog; Liprolog Mix 25 and 50; Mixtard 10, 20, 30, 40, and 50; Monotard HM†; NovoMix 30, 50, and 70; NovoRapid; Optisulin; Ultratard HM†; Velosulin; Denm.: Actrapid; Apidra; Humalog; Humalog Mix 25 and 50; Humulin Mix 30/70; Humulin NPH; Humulin Regular; Insulatard; Insuman Basal; Insuman Comb 25; Insuman Rapid; Lantus; Levemir; Mixtard 10, 20, 30, 40, and 50; Monotard; NovoMix 30; NovoRapid; Velosulin; Fin.: Actrapid; Humalog; Humalog Mix 25 and 50; Humulin NPH; Humulin Regular; Humutard†; Insulin Lyhyt†; Insulin Pitka†; Insuman Basal; Insuman Comb 25; Insuman Infusat; Insuman Rapid; Lantus; Levemir; Mixtard 10, 20, 30, and 50; Monotard; NovoMix 30; NovoRapid; Protaphane; Ultratard†; Velosulin†; Fr.: Actrapid; Apidra; Exubera; Humalog; Humalog Mix 25 and 50; Insulatard; Insuman Basal; Insuman Comb 15, 25, and 50; Insuman Infusat; Insuman Rapid; Insuplant; Lantus; Levemir; Lillypen Rapide†; Mixtard 10, 20, 30, 40, and 50; Monotard†; NovoMix 30; NovoRapid; Ultratard†; Umuline NPH; Umuline Profil 30; Umuline Rapide; Umuline Zinc Compose†; Umuline Zinc†; Velosulin†; Ger.: Actraphane 10, 20, 30, 40, 50; Actrapid; Apidra; B-Insulin†; Berlinsulin H 30/70; Berlinsulin H Basal; Berlinsulin H Normal; Depot-Insulin S†; Depot-Insulin†; H-Tronin†; Humalog; Humalog Mix 25 and 50; Huminsulin Basal; Huminsulin Normal; Huminsulin Profil III; Insulatard Human†; Insulin Basal; Insulin Comb 30/70; Insulin Monotard HM†; Insulin Novo Semilente MC; Insulin Rapid; Insulin S†; Insulin SNC†; Insuman Basal; Insuman Comb 15, 25, and 50; Insuman Infusat; Insuman Rapid; Komb-Insulin S†; Komb-Insulin†; Lantus; Levemir; Liprolog; Liprolog Mix 25 and 50; Mixtard 30/70†; Monotard; NovoMix 30; NovoRapid; Protaphane; Semilente†; Ultratard; Velosulin; Gr.: Actraphane HM†; Actrapid; Apidra; Exubera; Humalog; Humalog Mix 25 and 50; Humalog NPL; Humulin Lente; Humulin M2, M3; Humulin NPH; Humulin Regular; Humulin Utralente; Lantus; Levemir; Mixtard 10, 20, 30, 40, and 50; Monotard; NovoMix 30; NovoRapid; PenMix 10, 20, 30, 40, or 50†; Protaphane; Ultratard; Hong Kong: Actrapid HM; Actrapid MC†; Humalog; Humulin 70/30; Humulin L; Humulin N; Humulin R; Insulatard MC†; Lantus; Mixtard 30 HM; Monotard HM; Monotard MC†; NovoMix 30; NovoRapid; Protaphane HM; Ultratard HM; Hung.: Actrapid; Apidra; Humalog; Humalog Mix25 and Mix50; Humulin L†; Humulin M3; Humulin N; Humulin R; Humulin U†; Insulatard; Insulin Monotard†; Insulin Semilente†; Insulin Ultratard†; Lantus; Levemir; Mixtard 10, 20, 30, 40, and 50; Monotard MC†; NovoMix 30; NovoRapid; India: Actrapid; Human Actrapid; Human Insultard; Human Mixtard 30 and 50; Human Monotard; Insuman Rapid; Insuman 25/75 and 50/50; Lantus; Lentard; Mixulin; Rapidica; Rapimix; Wosulin Biphasic 30/70 and 50/50; Wosulin-N; Wosulin-R; Zinulin; Indon.: Actrapid HM; Apidra; Humalog; Humalog Mix 25; Humulin 30/70; Humulin N; Humulin R; Insulatard HM; Lantus; Mixtard 30 HM; Monotard HM; Irl.: Actrapid; Apidra; Humalog; Humalog Mix 25 and 50; Humulin I; Humulin Lente†; Humulin M3; Humulin S; Humulin Zn†; Insulatard; Insuman Basal; Insuman Comb 15, 25, and 50; Insuman Rapid; Lantus; Levemir; Mixtard 10 , 20, 30, 40, and 50; Monotard†; NovoMix 30; NovoRapid; Ultratard†; Israel: Humalog; Humalog Mix 25; Humulin 70/30; Humulin N; Humulin R; Humulin U†; Lantus; Levemir; NovoMix 30; NovoRapid; Ital.: Actraphane 10, 20, 30, 40, 50; Actrapid; Apidra; Bio-Insulin 30/70 and 50/50†; Bio-Insulin I†; Bio-Insulin L†; Bio-Insulin R†; Bio-Insulin U†; Humalog; Humalog Mix 25 and 50; Humulin 30/70 and 50/50; Humulin I; Humulin L†; Humulin R; Humulin U†; Lantus; Levemir; Monotard; NovoMix 30; NovoRapid; Protaphane; Ultratard; Jpn: Humacart 3/7; InnoLet 10R, 20R, 30R, 40R, and 50R; InnoLet N; InnoLet R; Monotard†; NovoLet 10R,20R, 30R, 40R, 50R†; NovoLet N†; NovoLet R†; Novolin 10R, 20R, 30R, 40R, and 50R; Novolin N; Novolin R; Novolin U†; NovoRapid; NovoRapid 30 Mix chu; Penfill N; Penfill R; Penfill 10R, 20R, 30R, 40R, 50R; Velosulin; Malaysia: Actrapid HM; Humalog; Humulin 30/70; Humulin L†; Humulin N; Humulin R; Insulatard; Lantus; Levemir; Mixtard 30 HM; Monotard HM†; NovoMix; NovoRapid; Ultratard HM†; Mex.: Glinux 70/30; Glinux-N; Humalog; Humalog Mix 25; Humanilusin; Humulin 70/30, 80/20; Humulin L; Humulin N; Humulin R; Insulex; Insuman 100N; Insuman 15R/85N, 25R/75N, and 50R/50N; Insuman R; Lantus; Levemir; Novolin 30/70; Novolin L†; Novolin N; Novolin R; NovoMix 30; NovoRapid; Prodiabin-N; Neth.: Actraphane 10, 20, 30, 40, 50; Actrapid; Apidra; Humalog; Humalog Mix 25 and 50; Humalog NPL; Humuline; Humuline 30/70; Humuline NPH; Insulatard; Insuman Basal; Insuman Comb 15, 25, and 50; Insuman Infusat; Insuman Rapid; Isuhuman Infusat†; Lantus; Levemir; Liprolog; Liprolog Mix 25 and 50; Mixtard 10, 20, 30, 40, and 50; Monotard; NovoMix 30, 50, and 70; NovoRapid; Optisulin; Protaphane; Ultratard; Velosulin; Norw.: Actrapid; Humalog; Humalog Mix 25; Humulin NPH; Insulatard; Insuman Basal; Insuman Comb 25; Insuman Infusat; Insuman Rapid; Lantus; Levemir; Mixtard 10, 20, 30, 40, and 50; Monotard†; NovoMix 30; NovoRapid; Ultratard†; Velosulin†; NZ: Actrapid; Humalog; Humalog Mix 25 and 50; Humulin 70/30; Humulin L†; Humulin NPH; Humulin R; Humulin U†; Insulatard MC; Lantus; Levemir; Mixtard 30 or 50; Monotard; NovoRapid; PenMix 10, 20, 30, 40, or 50; Protaphane; Ultratard; Velosulin HM; Velosulin MC; Philipp.: Actrapid HM; Biosulidd L; Humalog; Humulin 70/30; Humulin N (NPH); Humulin R (Regular); Insulatard HM; Lantus; Mixtard 30 HM; NovoMix 30; SciLin M30; SciLin N; SciLin R; Pol.: Actrapid; Apidra; Gensulin N; Gensulin R; Gensulin M10, M20, M30, M40, or M50; Humaject M3 (30/70)†; Humaject R†; Humalog; Humalog Mix 25 and 50; Humulin M3 (30/70); Humulin N; Humulin R; Insulatard; Insulinum Lente; Insulinum Maxirapid; Insulinum Semilente; Insulinum Ultralente; Insuman Basal; Insuman Comb 25; Insuman Rapid; Lantus; Levemir; Mixtard 10, 20, 30, 40, and 50; NovoMix 30; NovoRapid; Polhumin Mix-3; Polhumin N; Polhumin R; Ultratard HM; Port.: Actrapid; Apidra; Exubera; Humalog; Humulin Lenta†; Humulin M3; Humulin NPH; Humulin Regular; Humulin Ultralenta†; Insulatard; Isuhuman Basal†; Isuhuman Comb 25†; Isuhuman Rapid†; Lantus; Levemir; Liprolog; Liprolog Mix 25 and 50; Mixtard 10 , 20, 30, 40, and 50 HM; Monotard†; NovoMix 30, 50, and 70; NovoRapid; Optisulin; Protaphane; Ultratard†; Velosulin; Rus.: Actrapid HM (Актрапид НМ); Actrapid MC (Актрапид MC); Biosulin N (Биосулин Н); Biosulin R (Биосулин Р); Humalog (Хумалог); Humalog Mix 25 (Хумалог Микс 25); Humulin M3 (Хумулин М3); Humulin NPH (Хумулин НПХ); Humulin Regular (Хумулин Регуляр); Insulidd L (Инсулидд Л); Insulidd N (Инсулидд Н)†; Insulidd R (Инсулидд Р)†; Insulin Lt (Инсулин Лт); Insulin Maxirapid (Инсулин Максирапид); Insuman Basal (Инсуман Базал); Insuman Comb 25 (Инсуман Комб 25); Insuman Rapid (Инсуман Рапид); Lantus (Лантус); Levemir (Левемир); Levulin L (Левулин Л); Levulin N (Левулин Н)†; Levulin R (Левулин Р)†; Mixtard 30 HM (Микстард 30 НМ); Monotard MC (Монотард Нм); NovoMix 30 (НовоМикс 30); NovoRapid (Новорапид); Protaphane HM (Протафан НМ); S.Afr.: Actraphane HM; Actrapid HM; Apidra; Humalog; Humalog Mix 25; Humulin 30/70; Humulin L†; Humulin N; Humulin R; Lantus; Levemir; Mixtard 20/80†; Monotard HM†; NovoMix 30; NovoRapid; Protaphane HM; Ultratard HM†; Singapore: Actrapid HM; Humalog; Humalog Mix 25; Humulin 30/70; Humulin L†; Humulin N; Humulin R; Insulatard HM; Lantus; Levemir; Mixtard 30 or 50; Monotard HM†; NovoMix 30; NovoRapid; Ultratard HM†; Spain: Actrapid; Humalog; Humalog Mix 25 and 50; Humalog NPL; Humaplus 30/70†; Humaplus NPH†; Humaplus Regular†; Humulina 30:70; Humulina Lenta†; Humulina NPH; Humulina Regular; Humulina Ultralenta†; Insulatard; Insulatard NPH†; Lantus; Levemir; Mixtard 30; Mixtard 30/70†; Monotard†; NovoMix 30; NovoRapid; Ultratard†; Swed.: Actrapid; Apidra; Humalog; Humalog Mix 25 and 50; Humulin Mix 30/70; Humulin NPH; Humulin Regular; Insulatard; Insuman Basal; Insuman Comb 25; Insuman Infusat; Insuman Rapid; Lantus; Levemir; Mixtard 10, 20, 30, 40, and 50; Monotard; NovoMix 30; NovoRapid; Ultratard; Velosulin†; Switz.: Actrapid HM; Actrapid MC; Apidra; Humalog; Huminsulin Basal (NPH); Huminsulin Long; Huminsulin Normal; Huminsulin Profil III; Huminsulin Ultralong; Hypurin 30/70 Mix; Hypurin Isophane; Hypurin Neutral; Insulatard HM; Insulatard MC; Insuman Basal; Insuman Comb 25; Insuman Infusat; Insuman Rapid; Lantus; Lente MC†; Levemir; Mixtard 30 MC; Mixtard HM 10, 20, 30, 40, 50; Monotard HM; NovoMix 30; NovoRapid; Semilente MC; Ultratard HM; Velosulin HM†; Thai.: Actrapid HM; Humalog; Humalog Mix 25; Humulin 70/30; Humulin N; Humulin R; Insulatard; Lantus; Mixtard HM; Monotard HM†; NovoMix 30; NovoRapid; Turk.: Humalog; Humalog Mix 25 and 50; Humulin M 70/30 and 80/20; Humulin N; Humulin R; Insulatard; Lantus; Mixtard 10, 20, 30, 40, and 50; NovoMix 30; NovoRapid; Orgasulin Mix 30/70; UAE: Jusline 70/30; Jusline N; Jusline R; UK: Actrapid; Apidra; Exubera†; Humaject S†; Humalog; Humalog Mix 25 and 50; Humulin I; Humulin Lente†; Humulin M3; Humulin S; Humulin Zn†; Hypurin 30/70; Hypurin Isophane; Hypurin Lente; Hypurin Neutral; Hypurin Protamine Zinc; Insulatard; Insuman Basal; Insuman Comb 15, 25, and 50; Insuman Rapid; Lantus; Levemir; Mixtard 30; Monotard†; NovoMix 30; NovoRapid; Pork Actrapid†; Pork Insulatard†; Pork Mixtard 30†; Ultratard†; Velosulin†; USA: Apidra; Exubera; Humalog; Humalog Mix 75/25 and 50/50; Humulin 70/30, 50/50; Humulin L†; Humulin N; Humulin R; Humulin U Ultralente†; Lantus; Lente; Lente Iletin II; Levemir; Novolin 70/30; Novolin N; Novolin R; NovoLog; NovoLog Mix 70/30; NPH Iletin II†; Regular Iletin II; Ultralente; Velosulin Human BR†; Venez.: Humalog; Humalog Mix 25; Humulin 70/30; Humulin L†; Humulin N; Humulin R; Insuman N; Insuman R; Lantus; Novolin 70/30†; Novolin L†; Novolin N†; Novolin R†.
Published November 11, 2018.