Challenging The Pathophysiology of T2DM: The Role of Basal Insulin Therapy
Current guidelines uniformly recommend a stepwise approach to initiating insulin therapy in T2DM, beginning with basal insulin.5,6 The ideal basal insulin matches physiological basal needs—and thus provides biological activity and coverage for a full 24 hours—and requires a minimal number of injections (eg, once-daily).13,14 The ideal basal insulin would also work as consistently in the first 12 hours as in the last 12 hours, and work consistently from day to day and from patient to patient.13,14
Currently, there are several different basal insulins approved by the US Food and Drug Administration (Table 1).15 The most commonly used insulins contain 100 units of insulin per mL (U-100). Concentrated insulins are also available, at concentrations of 200 units/mL (U-200), 300 units/mL (U-300), and 500 units/mL (U-500).15 HCPs should be aware of important differences in the time-action profiles of basal insulins (Table 1, Figure 1).15 It is also important to note that switching from one basal insulin to another may require dose adjustment.15
There are pre-assessment questions associated with the content of this program that should be accessed at www.caringfordiabetes.com/CRinsulin prior to participating in this activity.
This activity is provided by the Institute for Medical and Nursing Education, Inc.
Current type 2 diabetes mellitus (T2DM) guidelines emphasize individualizing care and prioritizing treatment regimens that minimize hypoglycemia and weight gain. Several new insulins have recently been approved, some of which are available in concentrations not previously available in the United States. Among these are next generation longer-acting (ultralong-acting) basal insulin analogues, which are associated with a lower risk of hypoglycemia than previous long- acting basal insulin analogues. With the availability of new basal insulins, there is a need to educate nurse practitioners (NPs) and physician assistants (PAs) about initiating, titrating, and individualizing insulin therapy.
This activity will review current evidence and best practices for individualizing and intensifying antihyperglycemic therapy using current basal insulin options to achieve patient-centered goals in individuals with T2DM. Additionally, participants in this activity will learn about the rationale for and role of different basal insulins for the treatment of patients with T2DM. To enhance the written information, embedded QR codes will feature video clips of patient cases and audio clips of faculty discussion, offering realistic insight regarding the personal and professional experiences of participants and expert opinions of program faculty in providing optimal diabetes care in patients with T2DM.
- Explain the role and appropriate use of next-generation longer-acting (ultralong-acting) basal insulins for addressing the underlying pathophysiology of T2DM
- Compare next-generation longer-acting (ultralong-acting) and other basal insulins regarding therapeutic characteristics, including pharmacokinetic/pharmacodynamic profiles, efficacy, safety, and dosing
- Develop patient-centered treatment regimens that include next-generation longer-acting (ultralong-acting) insulins to minimize barriers to successful use of basal insulin therapy
CME AND CE ACCREDITATION AND CREDIT DESIGNATION STATEMENTS
The Institute for Medical and Nursing Education, Inc. (IMNE), is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
IMNE designates this educational activity for a maximum of 1.5 AMA PRA Category 1 Credits™.
Physicians should claim only the credit commensurate with the extent of their participation in the activity.
For Physician AssistantsThe American Academy of Physician Assistants (AAPA) has determined that AMA PRA Category 1 Credit(s)™ is acceptable to meet AAPA CME requirements for PAs.
For Nurse Practitioners and Nurses
IMNE is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s (ANCC’s) Commission on Accreditation.
This educational program provides 1.5 contact hours of continuing education credit.
IMNE has determined the 1.25 hours of this program will satisfy ANCC’s pharmacotherapeutics contact hour requirement for ANCC certified Clinical Nurse Specialists and Nurse Practitioners. The CEU certificate will reflect this credit.
For Certified Diabetes Educators
ANCC-accredited providers have been approved by the National Certification Board for Diabetes Educators (NCBDE) as providers of continuing education (CE). Individuals seek-ing recertification from the NCBDE can use the CE contact hours received through their participation in this activity.
METHOD OF PARTICIPATION
To receive a maximum of 1.5 AMA PRA Category 1 Credits™ or ANCC continuing nursing education credit, participants should:
- Complete the preassessment questions at www.caringfordiabetes.com/CRinsulin
- Read the entire activity
- Complete the activity posttest and evaluation at http://www.cvent.com/d/pbqrw7/7E
- A CME/CE certificate will be emailed or mailed to you upon achieving a score of 80%.
CME/CE CREDIT QUESTIONS
For questions about the content or obtaining CME/CE credit, please contact IMNE:
Steve Weinman RN, CHCP
Email: [email protected]
Activity Release Date: December 1, 2018
Expiration Date: November 30, 2019
It is the policy of IMNE to ensure fair balance, independence, objectivity, and scientific rigor in all programming. All individuals involved in planning (eg, faculty, CME/CE provider staff, and educational partner staff) are expected to disclose any significant financial relationships with commercial interests over the past 12 months. It is also required that faculty identify and reference off-label product or investigational uses of pharmaceutical agents and medical devices.
Resolutions of conflict of interest have been made in the form of external peer review.
The following disclosures have been made:
Vanita Aroda, MD
Consultant: Novo Nordisk; Sanofi
Research Grants: AstraZeneca/Bristol-Myers Squibb; Calibra; Eisai; Janssen; Novo Nordisk; Sanofi; Theracos
Davida Kruger, MSN, APN-BC, BC-ADM
Advisory Board: Abbott; Dexcom; Eli Lilly; Intarcia; Janssen; Novo Nordisk; Sanofi
Speakers’ Bureau: Abbott; AstraZeneca; Boehringer Ingelheim; Dexcom; Eli Lilly; Insulet; Janssen; Novo Nordisk; Valeritas
Research Grants: AstraZeneca; Dexcom; Eli Lilly; The Leona M. and Harry B. Helmsley Charitable Trust; Lexicon; Novo Nordisk
All staff of IMNE in a position to influence content have filed statements of disclosure with the continuing education provider. Any conflicts of interest were identified and resolved prior to their involvement in planning this activity. These disclosures are available for review by contacting Steve Weinman at 1-609-936-7015 or [email protected].
Ms. Carbonara has nothing to disclose.
Margery Tamas, HBSE, MPH
Ms. Tamas has nothing to disclose.
Steve Weinman, RN, CHCP
Director of Accreditation
Mr. Weinman has nothing to disclose.
External CME/CE Reviewers
Martin Quan, MD
Dr. Quan has nothing to disclose.
Darilyn Paul, APRN
Ms. Paul has nothing to disclose.
This activity is designed for HCPs for educational purposes. Information and opinions offered by the faculty/presenters represent their own viewpoints. Conclusions drawn by the participants should be derived from careful consideration of all available scientific information. While IMNE makes every effort to have accurate information presented, no warranty, expressed or implied, is offered. The participant should use his/her clinical judgment, knowledge, experience, and diagnostic decision-making before applying any information, whether provided here or by others, for any professional use.
COMMERCIAL SUPPORT ACKNOWLEDGMENT
This activity is supported by an educational grant from Sanofi US.
- Hanefeld M, Monnier L, Schnell O, Owens D. Early treatment with basal insulin glargine in people with type 2 diabetes: lessons from ORIGIN and other cardiovascular trials. Diabetes Ther. 2016;7(2):187-201.
- Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003;46(1):3-19.
- Mitrakou A, Kelley D, Mokan M, et al. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med. 1992;326(1):22-29.
- Kramer CK, Zinman B, Choi H, Retnakaran R. Effect of short-term intensive insulin therapy on post-challenge hyperglucagonemia in early type 2 diabetes. J Clin Endocrinol Metab.2015;100(8):2987-2995.
- American Diabetes Association. Standards of medical care in diabetes—2018. Diabetes Care. 2018;41(suppl 1):S1-S159.
- Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2018 executive summary. Endocr Pract. 2018;24(1):91-120.
- Kendall DM, Cuddihy RM, Bergenstal RM. Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Am J Med. 2009;122(6 suppl):S37-S50.
- Hirsch IB, Bergenstal RM, Parkin CG, Wright E, Buse JB. A real-world approach to insulin therapy in primary care practice. Clin Diabetes. 2005;23(2):78-86.
- Turner RC, Cull CA, Frighi V, Holman RR; for the UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281(21):2005-2012.
- ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319-328.
- Nichols GA, Kimes TM, Harp JB, Kou TD, Brodovicz KG. Glycemic response and attainment of A1C goals following newly initiated insulin therapy for type 2 diabetes. Diabetes Care. 2012;35(3): 495-497.
- Frid A, Hirsch L, Gaspar R, et al. New injection recommendations for patients with diabetes. Diabetes Metab. 2010;36(suppl 2):S3-S18.
- Zinman B. The physiologic replacement of insulin. An elusive goal. N Engl J Med. 1989;321(6):363-370.
- Garber AJ. Will the next generation of basal insulins offer clinical advantages? Diabetes Obes Metab. 2014;16(6):483-491.
- US Food and Drug Administration. [email protected]: FDA approved drug products. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed September 4, 2018.
- Becker RH, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T. New insulin glargine 300 units•mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 units•mL-1. Diabetes Care.2015;38(4):637-643.
- 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(6):1614-1620.
- Heise T, Pieber TR. Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies. Diabetes Obes Metab. 2007;9(5):648-659.
- Laubner K, Molz K, Kerner W, et al. Daily insulin doses and injection frequencies of neutral protamine Hagedorn (NPH) insulin, insulin detemir and glargine in type 1 and type 2 diabetes: a multicenter analysis of 51,964 patients from the German/Austrian DPV-Wiss database. Diabetes Metab Res Rev. 2014;30(5):395-404.
- Lucidi P, Porcellati F, Marinelli Andreoli A, et al. Pharmacokinetics and pharmacodynamics of NPH insulin in type 1 diabetes: the importance of appropriate resuspension before subcutaneous injection. Diabetes Care. 2015;38(12):2204-2210.
- Heise T, Norskov M, Nosek L, Kaplan K, Famulla S, Haahr HL. Insulin degludec: lower day-to-day and within-day variability in pharmacodynamic response compared with insulin glargine 300 U/mL in type 1 diabetes. Diabetes Obes Metab. 2017;19(7):1032-1039.
- Bailey TS, Pettus J, Roussel R, et al. Morning administration of 0.4U/kg/day insulin glargine 300U/mL provides less fluctuating 24-hour pharmacodynamics and more even pharmacokinetic profiles compared with insulin degludec 100U/mL in type 1 diabetes. Diabetes Metab. 2018;44(1):15-21.
- Heise T, Heckermann S, Hans DeVries J. Variability of insulin degludec and glargine 300 U/mL: a matter of methodology or just marketing? Diabetes Obes Metab. 2018;20(9):2051-2056.
- Lasalvia P, Barahona-Correa JE, Romero-Alvernia DM, et al. Pen devices for insulin self-administration compared with needle and vial: systematic review of the literature and meta-analysis. J Diabetes Sci Technol. 2016;10(4):959-966.
- Klonoff DC, Blonde L, Cembrowski G, et al. Consensus report: the current role of self-monitoring of blood glucose in non-insulin-treated type 2 diabetes. J Diabetes Sci Technol. 2011;5(6):1529-1548.
- Hinnen D, Tomky D. Intensifying therapy. In: Mensing C, ed. The Art and Science of Diabetes Self-Management Education Desk Reference. 2nd ed. Chicago, IL: American Association of Diabetes Educators; 2011:531-575.
- Roche Diabetes Care. Accu-Chek Connect. Quick Reference Guide for Using Structured SMBG to Improve Patient Outcomes. Pattern for Success. 2011. http://behavioraldiabetesinstitute.org/studies/downloads/ACCU-CHEK_Quick_Reference_Guide.pdf. Accessed July 5, 2018.
- American Diabetes Association. Practical Insulin: a Handbook for Prescribing Providers. 3rd ed. Alexandria, VA: American Diabetes Association; 2011.
- eaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36(5):1384-1395.
- Zhang T, Zhao Y, Du T, et al. Lack of coordination between partners: investigation of Physician-Preferred and Patient-Preferred (4P) basal insulin titration algorithms in the real world. Patient Prefer Adherence. 2018;12:1253-1259.
- Yki-Jarvinen H, Bergenstal R, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/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(12):3235-3243.
- Vora J, Cariou B, Evans M, et al. Clinical use of insulin degludec. Diabetes Res Clin Pract. 2015;109(1):19-31.
- Geller AI, Shehab N, Lovegrove MC, et al. National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations. JAMA Intern Med. 2014;174(5):678-686.
- Webb RT, Lichtenstein P, Dahlin M, Kapur N, Ludvigsson JF, Runeson B. Unnatural deaths in a national cohort of people diagnosed with diabetes. Diabetes Care. 2014;37(8):2276-2283.
- Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS. US emergency department visits for outpatient adverse drug events, 2013-2014. JAMA. 2016;316(20):2115-2125.
- Boulin M, Diaby V, Tannenbaum C. Preventing unnecessary costs of drug-induced hypoglycemia in older adults with type 2 diabetes in the United States and Canada. PLoS One. 2016;11(9):e0162951.
- Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab.2009;94(3):709-728.
- Lee AK, Warren B, Lee CJ, et al. The association of severe hypoglycemia with incident cardiovascular events and mortality in adults with type 2 diabetes. Diabetes Care. 2017;41(1):104-111.
- Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377(8):723-732.
- Brod M, Christensen T, Bushnell DM. Impact of nocturnal hypoglycemic events on diabetes management, sleep quality, and next-day function: results from a four-country survey. J Med Econ. 2012;15(1):77-86.
- Alvarez-Guisasola F, Yin DD, Nocea G, Qiu Y, Mavros P. Association of hypoglycemic symptoms with patients’ rating of their health-related quality of life state: a cross sectional study. Health Qual Life Outcomes. 2010;8:86.
- Marrett E, Radican L, Davies MJ, Zhang Q. Assessment of severity and frequency of self-reported hypoglycemia on quality of life in patients with type 2 diabetes treated with oral antihyperglycemic agents: a survey study. BMC Res Notes. 2011;4:251.
- Moennig E, Perez-Nieves M, Hadjiyianni I, Cao D, Ivanova J, Klask R. Initiation of basal insulin analog treatment for type 2 diabetes and reasons behind patients’ treatment persistence behavior: real-world data from Germany. Exp Clin Endocrinol Diabetes.2018;126(5):287-297.
- Dalal MR, Kazemi M, Ye F, Xie L. Hypoglycemia after initiation of basal insulin in patients with type 2 diabetes in the United States: implications for treatment discontinuation and healthcare costs and utilization. Adv Ther. 2017;34(9):2083-2092.
- Freemantle N, Chou E, Frois C, et al. Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.BMJ Open. 2016;6(2):e009421.
- Madenidou AV, Paschos P, Karagiannis T, et al. Comparative benefits and harms of basal insulin analogues for type 2 diabetes: a systematic review and network meta-analysis. Ann Intern Med. 2018;169(3): 165-174.
- Ritzel R, Roussel R, Bolli GB, et al. Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes. Diabetes Obes Metab. 2015;17(9): 859-867.
- Rys P, Wojciechowski P, Rogoz-Sitek A, et al. Systematic review and meta-analysis of randomized clinical trials comparing efficacy and safety outcomes of insulin glargine with NPH insulin, premixed insulin preparations or with insulin detemir in type 2 diabetes mellitus. Acta Diabetol. 2015;52(4):649-662.
- Rosenstock J, Hollander P, Bhargava A, et al. Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin-naive or previously treated with insulin glargine: a randomized, double-blind controlled trial (the ELEMENT 2 study). Diabetes Obes Metab. 2015;17(8):734-741.
- Zhang XW, Zhang XL, Xu B, Kang LN. Comparative safety and efficacy of insulin degludec with insulin glargine in type 2 and type 1 diabetes: a meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):429-441.
- Heller S, Mathieu C, Kapur R, Wolden ML, Zinman B. A meta-analysis of rate ratios for nocturnal confirmed hypoglycaemia with insulin degludec vs. insulin glargine using different definitions for hypoglycaemia. Diabet Med. 2016;33(4):478-487.
- Rosenstock J, Cheng A, Ritzel R, et al. More similarities than differences testing insulin glargine 300 units/mL versus insulin degludec 100 units/mL in insulin-naive type 2 diabetes: the randomized head-to-head BRIGHT trial. Diabetes Care. 2018;41(10):2147-2154.
- Powers MA, Bardsley J, Cypress M, et al. Diabetes self-management education and support in type 2 diabetes: a joint position statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics. Diabetes Care. 2015;38(7):1372-1382.
- Centers for Disease Control and Prevention. National diabe-tes statistics report, 2014. https://www.cdc.gov/diabetes/pdfs/data/2014-report-estimates-of-diabetes-and-its-burden-in-the-united-states.pdf. Accessed September 27, 2018.
- Ceriello A, Monnier L, Owens D. Glycaemic variability in diabetes: clinical and therapeutic implications. Lancet Diabetes Endocrinol. 2018 Aug 13. [Epub ahead of print].
- Zinman B, Marso SP, Poulter NR, et al. Day-to-day fasting glycaemic variability in DEVOTE: associations with severe hypoglycaemia and cardiovascular outcomes (DEVOTE 2). Diabetologia.2017;61(1):48-57.
- Zhou JJ, Schwenke DC, Bahn G, Reaven P; VADT Investigators. Glycemic variation and cardiovascular risk in the Veterans Affairs Diabetes Trial. Diabetes Care. 2018;41(10):2187-2194.
- Gajos G. Diabetes and cardiovascular disease: from new mechanisms to new therapies. Pol Arch Intern Med. 2018;128(3):178-186.
- Zisman A, Morales F, Stewart J, Stuhr A, Vlajnic A, Zhou R. BeAM value: an indicator of the need to initiate and intensify prandial therapy in patients with type 2 diabetes mellitus receiving basal insulin. BMJ Open Diabetes Res Care. 2016;4:e000171.
- Tanenberg RJ, Zisman A, Stewart J. Glycemia optimization treatment (GOT): glycemic control and rate of severe hypoglycemia for five different dosing algorithms of insulin glargine (GLAR) in patients with type 2 diabetes mellitus (T2DM). Diabetes.2006;55(suppl 1):A135 [abstract 567-P].
- UKPDS Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UK-PDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-853.
- UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet.1998;352(9131):854-865.
- Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial. JAMA. 2017;318(1):45-56.
- Zhou FL, Ye F, Berhanu P, et al. Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin. Diabetes Obes Metab. 2018;20(5):1293-1297.
- Sullivan SD, Bailey TS, Roussel R, et al. Clinical outcomes in real-world patients with type 2 diabetes switching from first- to second-generation basal insulin analogues: comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIV-ER D+ cohort study. Diabetes Obes Metab. 2018;20(9):2148-2158.
- Zhang Q, Rosenstock J, Liao L, Chew P. Is hypoglycaemia a modifiable patient risk in type 2 diabetes: a pooled analysis of insulin glargine 300 U/mL (Gla-300) vs 100 U/mL (Gla-100) trials? [ePoster 974]. Poster presented at: 51st EASD Annual Meeting; September 14-18, 2015; Stockholm, Sweden. http://www.easdvirtualmeet-ing.org/resources/is-hypoglycaemia-a-modifiable-patient-risk-in-type-2-diabetes-a-pooled-analysis-of-insulin-glargine-300-u-ml-gla-300-vs-100u-ml-gla-100-trials--3. Accessed June 17, 2016.
- Pieber TR, Marso SP, McGuire DK, et al. DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular out-comes and mortality. Diabetologia. 2017;61(1):58-65.
- Sorli C, Warren M, Oyer D, Mersebach H, Johansen T, Gough SC. 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(12): 1009-1018.
- Ritzel R, Harris SB, Baron H, et al. A randomized controlled trial comparing efficacy and safety of insulin glargine 300 units/mL versus 100 units/mL in older people with type 2 diabetes: results from the SENIOR Study. Diabetes Care. 2018;41(8):1672-1680.
- Decision Resources Group. Fingertip formulary - formulary look-up. https://lookup.decisionresourcesgroup.com/. Accessed September 4, 2018.
- Managed Markets Insight & Technology, LLC. Formulary search. http://formularysearch.mmitnetwork.com/#top. Accessed September 4, 2018.
- Bibeau WS, Fu H, Taylor AD, Kwan AY. Impact of out-of-pocket pharmacy costs on branded medication adherence among patients with type 2 diabetes. J Manag Care Spec Pharm. 2016;22(11): 1338-1347.
- Wharam JF, Zhang F, Eggleston EM, Lu CY, Soumerai SB, Ross-Degnan D. Effect of high-deductible insurance on high-acuity outcomes in diabetes: a Natural Experiment for Translation in Diabetes (NEXT-D) study. Diabetes Care. 2018;41(5):940-948.
- Cochran E, Musso C, Gorden P. The use of U-500 in patients with extreme insulin resistance. Diabetes Care. 2005;28(5):1240-1244.
- Cusi K. Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis. Clin Liver Dis. 2009;13(4):545-563.
- Clore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Endocr Pract. 2009;15(5):469-474.
- Heise T, Nosek L, Dellweg S, et al. Impact of injection speed and volume on perceived pain during subcutaneous injections into the abdomen and thigh: a single-centre, randomized controlled trial. Diabetes Obes Metab. 2014;16(10):971-976.
- 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(18):1526-1535.
- Bergen PM, Kruger DF, Taylor AD, Eid WE, Bhan A, Jackson JA. Translating U-500R randomized clinical trial evidence to the practice setting: a diabetes educator/expert prescriber team approach. Diabetes Educ. 2017;43(3):311-323.
- Frid AH, Kreugel G, Grassi G, et al. New insulin delivery recommendations. Mayo Clin Proc. 2016;91(9):1231-1255.
- Trief PM, Cibula D, Rodriguez E, Akel B, Weinstock RS. Incorrect insulin administration: a problem that warrants attention. Clin Diabetes. 2016;34(1):25-33.
- Bezreh T, Laws MB, Taubin T, Rifkin DE, Wilson IB. Challenges to physician-patient communication about medication use: a window into the skeptical patient’s world. Patient Prefer Adherence. 2012;6:11-18.
- Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Insu-lin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabet Med. 2012;29(5):682-689.
- Riddle MC, Karl DM. Individualizing targets and tactics for high-risk patients with type 2 diabetes: practical lessons from AC-CORD and other cardiovascular trials. Diabetes Care. 2012;35(10): 2100-2107.
- Perez-Nieves M, Boye KS, Kiljanski J, Cao D, Lage MJ. Adherence to basal insulin therapy among people with type 2 diabetes: a retrospective cohort study of costs and patient outcomes. Diabetes Ther. 2018;9(3):1099-1111.
- Dunton GF. Sustaining health-protective behaviors such as physical activity and healthy eating. JAMA. 2018;320(7):639-640.
- Cheng AY. The rule of 3’s: insulin use in type 2 diabetes. Canadian Diabetes. 2011;24(1):3-9.
- Meehan CA, Cochran E, Mattingly M, Gorden P, Brown RJ. Mild caloric restriction decreases insulin requirements in patients with type 2 diabetes and severe insulin resistance. Medicine (Baltimore). 2015;94(30):e1160.
- Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31(1):1-13.
- Wolpert HA, Atakov-Castillo A, Smith SA, Steil GM. Dietary fat acutely increases glucose concentrations and insulin requirements in patients with type 1 diabetes: implications for carbo-hydrate-based bolus dose calculation and intensive diabetes management. Diabetes Care. 2013;36(4):810-816.
- Novo Nordisk. How to start and convert your adult patients to once-daily, long-acting Tresiba®. https://www.tresibapro.com/dosing-and-device/starting-adult-patients.html. Accessed September 24, 2018.
- Warren ML, Chaykin LB, Jabbour S, et al. Insulin degludec 200 units/mL is associated with lower injection frequency and improved patient-reported outcomes compared with insulin glargine 100 units/mL in patients with type 2 diabetes requiring high-dose insulin. Clin Diabetes. 2017;35(2):90-95.
- Quansah KA, Sauriol L, Kukaswadia AA, Bremner S, Millson B. Persistence with insulin glargine 300 IU/mL compared with other basal insulins—a Canadian retrospective cohort study. Diabetes. 2018;67(suppl 1):A475 [abstract 1786-P].
- Meneghini L, Atkin SL, Gough SC, et al. The efficacy and safety of insulin degludec given in variable once-daily dosing intervals compared with insulin glargine and insulin degludec dosed at the same time daily: a 26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes. Diabetes Care. 2013;36(4):858-864.
- Riddle MC, Bolli GB, Home PD, et al. Efficacy and safety of flexible versus fixed dosing intervals of insulin glargine 300 U/mL in people with type 2 diabetes. Diabetes Technol Ther. 2016;18:252-257.
- Logan T, Daisy B. Evaluating the managed care implications of longer-acting basal insulin analog therapies. Am J Manag Care. 2018;24(6 suppl):S93-S101.
- Karter AJ, Parker MM, Solomon MD, et al. Effect of out-of-pocket cost on medication initiation, adherence, and persistence among patients with type 2 diabetes: the Diabetes Study of Northern California (DISTANCE). Health Serv Res. 2018;53(2):1227-1247.