Insulin U100, 200, 300 or 500?

Umesh Dashora, Erwin Castro


This article reviews the currently available information about insulin preparations in a concentration higher than 100 units/mL. These might be particularly useful in people with significant insulin resistance and high insulin requirement. U-200 insulin has low variability and lower (nocturnal) or similar risk of hypoglycaemia compared with U-100 insulin but is currently more expensive. U-300 glargine insulin has low variability, less weight gain and lower nocturnal hypoglycaemia in some studies in comparison to U-100 glargine. It is priced lower than U-100 glargine. U-500R insulin has been in use for some time worldwide but is not licensed in the UK. It also has low variability and lower cost per unit of insulin compared with U-100R. There is no specific delivery device and it has a higher risk of hypoglycaemia and weight gain. More insulins are in development (U-500 short-acting analogue [Fluorolog] and U-400 pre-mix like insulin BIOD-531, amongst others).


U200, U300, U500, insulin, type 2 diabetes, weight, hypoglycaemia

Full Text:



Public Health England. Adult obesity and type 2 diabetes 2014. (accessed May 2015)

Segal AR, El Sayed N. Are you ready for more insulin concentrations? J Diabetes Sci Technol 2015;9:331-8.

Rodbard H, Handelsman Y, Gough S, et al. Reduced risk of hypoglycemia with insulin degludec vs. insulin glargine in patients with type 2 diabetes requiring high doses of basal insulin: meta-analysis of five randomized trials (abstract 241). AACE 21st Annual Scientific and Clinical Congress, 23–27 May 2012, Philadelphia, Pennsylvania.

Turner RC. The UK Prospective Diabetes Study: a review. Diabetes Care 1998;21:C35–C38.

UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–53.

Stratton IM, Adler AI, Neil HA, Matthews DR. Association of glycaemia with macrovascular and microvascular complications in type 2 diabetes (UKPDS 35): Prospective observational study. BMJ 2000;321:405-12.

Bloom A, Keen H. A change to 100-unit insulin dosage will reduce insulin errors. BMJ 1981;283:33-4. Watkins JD et al. American journal of public health 1967;57:452.

Dashora UK, Collins A, Castro E. U 500 for patients with insulin resistance. Poster presentation at ABCD Autumn Meeting, 7-8 November 2013, London.

Megarbane B, Deye N, Bloch V, et al. Intentional overdose with insulin: prognostic factors and toxicokinetic/toxicodynamic profiles. Critical Care 2007;11:R115.

Health and Social Care Information Centre. National Diabetes Audit 2012–2013. (accessed May 2015)

Kurtzhals P, Heise T, Strauss HM, et al. Multi-hexamer formulation is the underlying mechanism behind the ultra-long glucose-lowering effect of insulin degludec. Diabetes 2011;60:42-LB.

Heise T, Haermanski L, Nosek L, et al. Ultra long acting insulin degludec has a flat glucose lowering effect in type 2 diabetes. Diabetes Obes Metab 2012;14:944-50.

Heise T, Haermanski L, Nosek L, et al. Insulin degludec: four times less pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab 2012;14:859-64.

Korsatko S, Deller S, Koehler G, et al. Comparison of the steady-state pharmacokinetic and pharmacodynamic profiles of 100 and 200 u/ml formulations of ultra-long-acting insulin degludec. Clin Drug Investig 2013;33:515-21.

Korsatko S, Deller S, Mader JK, et al. Ultra-long pharmacokinetic properties of insulin degludec are comparable subjects and younger adults with type 1 diabetes mellitus. Drugs Aging 2014;31:47-53.

Bode BW, Chaykin LB, Sussman AM, et al. Efficacy and safety of insulin degludec 200 U/ml and insulin degludec 100 U/ml in patients with Type 2 diabetes (Begin: Compare). Endocrine Practice 2014;20:785-91.

Gough SC, Bhargava A, Jain R, et al. Low-volume insulin degludec 200 units/ml once daily improves glycemic control similarly to insulin glargine with a low risk of hypoglycemia in insulin-naive patients with type 2 diabetes: a 26-week, randomized, controlled, multinational, treat-to target trial: the BEGIN LOW VOLUME trial. Diabetes Care 2013;36:2536-42.

Sorli C, Warren M, Oyer D, et al. Elderly patients with diabetes experience a lower rate of nocturnal hypoglycaemia with insulin degludec than with insulin glargine: a meta-analysis of phase IIIa trials. Drugs Aging 2013;30:1009-18.

Jax T, Heise T, Dahmen R, et al. New insulin glargine formulation has a flat and prolonged steady state profile in subjects with type 1 diabetes [abstract]. Diabetologia 2013;56(Suppl):A1029.

Tillner JA, Bergmann K, Telchert I, et al. Euglycaemic clamp profile of new insulin glargine U300 formulation in patients with type 1 diabetes (T1DM) is different from glargine U100. Diabetes 2013;62:A234.

Becker RH, Nowotny I, Teichert L, et al. Low within and between-day variability in exposure to new insulin glargine 300 u.nL-1 [abstract]. Diabetes 2014;63(Suppl 1):A228.

Heise T, Nosek L, Ronn BB, et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with Type 1 diabetes. Diabetes 2004;53:1614-20.

Sutton G, Minguet J, Ferrero C, Bramlage P. U300, a novel long-acting insulin formulation. Expert Opin Biol Ther 2014;14:1849-60.

Riddle MC, Bolli GB, Yki-Jarvinen H, et al. Sustained glycemic control and less hypoglycemia with new insulin glargine 300 U/mL compared with 100 U/mL: 1-year results in people with T2DM using basal + mealtime insulin (EDITION 1) [abstract]. Diabetes 2014;63(Suppl 1):LB20.

Riddle MC, Bolli GB, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care 2014;37:2755-62.

Yki-Jarvinen H, Bergenstal R, Ziemen M, et al. New insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care 2014;37:3235-43.

Bolli GB, Riddle MC, Bergenstal R, et al. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs: a randomized controlled trial (EDITION 3). Diabetes Obes Metab 2015;17:386-94.

Terauchi Y, Koyama M, Cheng X, et al. EDITION JP 2 Study Group. Glycemic control and hypoglycaemia in Japanese people with T2DM receiving new insulin glargine 300 U/mL in combination with OADs (EDITION JP 2) [abstract]. Diabetes 2014;63(Suppl 1):LB24.

Home PD, Bergenstal RM, Riddle MC, et al. Glycaemic control and hypoglycaemia with new insulin glargine 300U/mL in people with Type1DM (EDITION 4) [abstract]. Diabetes 2014;63(Suppl 1):LB19-20.

Matsuhisa M, Koyama M, Cheng X, et al. New insulin glargine 300 u/mL: glycemic control and hypoglycemia in Japanese people with T1DM (EDITION JP 1) [abstract]. Diabetes 2014;63(Suppl 1):LB22.

de la Pena A, Riddle M, Morrow LA, Jiang HH. Pharmacokinetic and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects. Diabetes Care 2011;34:2496-501.

De la Pena A, Ma X, Reddy S, et al. Application of PK/PD modelling and simulation to dosing regimen optimisation of high-dose human regular U-500 insulin. J Diabetes Sci Technol 2014;8:821-9.

Jones P, Idris I. The use of U-500 regular insulin in the management of patients with obesity and insulin resistance. Diabetes Obes Metab 2013;15:882-7.

Reutrakul S, Wroblewski K, Brown RL. Clinical use of U-500 regular insulin: review and meta-analysis. J Diabetes Sci Technol 2012;6:412-20.

Eby EL, Wang P, Curtis BH, et al. Cost, healthcare resource utilization, and adherence of individuals with diabetes using U-500 or U-100 insulin: a retrospective database analysis. J Med Econ 2013;16:529-38.

Binder C, Brange J. Insulin chemistry and pharmacokinetics. In: Ellenberg’s and Rifkin’s Diabetes Mellitus. 5th ed. Porte D Jr, Sherwin RS, eds. Stamford, CT: Appleton & Lange, 1997, p. 689

Distiller LA. The use of highly concentrated U-500 regular insulin for the severely insulin resistant patient with type 2 diabetes. Endocr Pract. Published Online First 4 Nov 2014.

Knee TS, Seidensticker DF, Walton JL, et al. A novel use of U-500 insulin for continuous subcutaneous insulin infusion in patients with insulin resistance: a case series. Endocr Pract 2003;9:181-6.

Lalej-Bennis D, Selam JL, Fluteau-Nadler S, et al. Extreme insulin resistance: clinical management by external subcutaneous insulin infusion. Diabetes Metab 1997;23:533-6.

Nathan DM, Axelrod L, Flier JS, Carr DB. U-500 insulin in the treatment of antibody-mediated insulin resistance. Ann Intern Med 1981;94:653–6.

Boldo A, Comi RJ. Clinical experience with U500 insulin: risks and benefits. Endocr Pract 2012;18:56-61.

Eby EL, Curtis BH, Gelwicks SC, et al. Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study. BMJ Open Diabetes Res Care 2015;3:e000074.

Eli Lilly. Humalog 200 units/ml KwikPen. Summary of Product Characteristics 2014. (accessed June 2015)

Lane WS. Use of U-500 regular insulin by continuous subcutaneous insulin infusion in patients with type 2 diabetes and severe insulin resistance. Endocr Pract 2006;12:251-6.

Bulchandani DG, Konrady T, Hamburg MS. Clinical efficacy and patient satisfaction with U-500 insulin pump therapy in patients with type 2 diabetes. Endocr Pract 2007;13:721-5.

Lane WS, Weinrib SL, Rappaport JM, Przestrzelski T. A prospective trial of U500 insulin delivered by Omnipod in patients with type 2 diabetes mellitus and severe insulin resistance. Endocr Pract 2010;16:778-84.

Lane WS, Weinrib SL, Rappaport JM, et al. The effect of long-term use of U-500 insulin via continuous subcutaneous infusion on durability of glycemic control and weight in obese, insulin-resistant patients with type2 diabetes. Endocr Pract 2013;19:196-201.

Institute for Safe Medication Practices. As U-500 insulin safety concerns mount, it’s time to rethink safe use of strengths above U-100. 31 October 2013 [cited 3 July 2014]. In: Acute Care ISMP Medication Safety Alert. Horsham, PA: Institute for Safe Downloaded from by guest on 13 November 2014.

Masangkay EG. Sanofi’s NDA for basal insulin Toujeo™ accepted by FDA. 11 July 2014 [cited 13 July 2014].

Cochran E. U-500 insulin: when more with less yields success. Diabetes Spectrum 2009;22:116-22.

Segal AR, Brunner JE, Burch FT, Jackson JA. Use of concentrated insulin human regular (U-500) for patients with diabetes. Am J Health Syst Pharm 2010;67:1526-35.

Medicines and Healthcare Products Regulatory Agency. Drug Safety Update. High strength, fixed combination and biosimilar insulin products: minimising the risk of medication error.



  • There are currently no refbacks.

The Journal of the Association of British Clinical Diabetologists