What to do after basal insulin: 3 Tx strategies for type 2 diabetes

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Applied Evidence

What to do after basal insulin: 3 Tx strategies for type 2 diabetes

J Fam Pract. 2015 April;64(4):214-220

Lubaina Presswala, DO

Jay Shubrook, DO, FAAFP, FACOFP, BC-ADM

These strategies can help you optimize glucose control in your patient with type 2 diabetes when basal insulin alone isn’t sufficient.

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References

1. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE Comprehensive Diabetes Management Algorithm 2013. Endocr Pract. 2013;19:327-336.

2. Inzucchi SE, Bergenstal RM, Buse JB, et al; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient centered approach. A position statement of the ADA and the EASD. Diabetes Care. 2012;35:1364-1379.

3. Shubrook, J. Insulin for type 2 diabetes: How and when to get started. J Fam Pract. 2014; 63:76-81.

4. Nathan D, Buse J, Davidson M, et al; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203.

5. Rosenstock J, Fonseca VA, Gross JL, et al. Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice daily prandial insulin lispro. Diabetes Care. 2014;37:2317-2325.

6. Owens DR, Luzio SD, Sert-Langeron C, et al. Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month ‘proof-of-concept’ study. Diabetes Obes Metab. 2011;13:1020-1027.

7. Lankisch MR, Ferlinz KC, Leahy JL, et al; Orals Plus Apidra and LANTUS (OPAL) study group. Introducing a simplified approach to insulin therapy in type 2 diabetes: a comparison of two singledose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs. Diabetes Obes Metab. 2008;10:1178-1185.

8. Davidson MB, Raskin P, Tanenberg RJ, et al. A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure. Endocr Pract. 2011;17:395-403.

9. Owens DR. Stepwise intensification of insulin therapy in type 2 diabetes management--exploring the concept of basal-plus approach in clinical practice. Diabet Med. 2013;30:276-288.

10. Holst J. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409-1439.

11. Byetta [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2015.

12. Bydureon [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2014.

13. Victoza [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2015.

14. Tanzeum [package insert]. Wilmington, DE: GlaxoSmithKline; 2014.

15. Trulicity [package insert]. Indianapolis, IN: Eli Lilly and Company; 2014.

16. Vaidya A, McMahon GT. Initiating insulin for type 2 diabetes: Strategies for success. J Clin Outcomes Manag. 2009;16:127-136.

17. Unger J. Insulin initiation and intensification in patients with T2DM for the primary care physician. Diabetes Metab Syndr Obes. 2011;4:253-261.

18. Sharma MD, Garber AJ. Progression from basal to pre-mixed or rapid-acting insulin – Options for intensification and the use of pumps. US Endocrinology. 2009;5:40-44.

19. Mooradian AD, Bernbaum M, Albert SG. Narrative review: A rational approach to starting insulin therapy. Ann Intern Med. 2006;145:125-134.

20. Monthly Prescribing Reference (MPR). Insulin. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/insulins/article/123739/. Accessed January 10, 2014.

21. Guyton AC, Hall JE. Insulin, glucagon, and diabetes mellitus. In: Guyton AC, Hall JE, eds. Textbook of Medical Physiology. 11th ed. Philadelphia, PA: Elsevier Saunders; 2006:961-977.

22. Kitabchi AE, Gosmanov AR. Safety of rapid-acting insulin analogs versus regular human insulin. Am J Med Sci. 2012;344:136-141.

23. Cryer PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N Eng J Med. 2004;350:2272-2279.

24. Gehlaut RR, Shubrook JH. Revisiting hypoglycemia in diabetes. Osteopathic Family Physician. 2014;1:19-25.

PRACTICE RECOMMENDATIONS

› Intensify diabetes treatment for patients who have a normal fasting glucose, but an HbA1c >7% and daytime hyperglycemia, and for those who are not at goal despite basal insulin doses >0.5 units/kg/d. B
› Consider intensifying diabetes management beyond basal insulin therapy by adding a glucagon-like peptide 1 receptor agonist, insulin prior to one meal each day, or insulin prior to all meals. C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Diabetes mellitus is a complex, progressive disease that affects every family physician’s practice. Major diabetes organizations recommend that treatment be ongoing and progressive in order to control the disease. The American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), and the American Association of Clinical Endocrinologists recommend that patients be assessed every 2 to 3 months after diagnosis and that treatment should be intensified if the patient is not meeting treatment goals.^1,2 Using this approach, all people with type 2 diabetes could be on insulin one year after diagnosis.^1,2

While many family physicians have become comfortable with using once-daily basal insulin such as glargine or detemir, what to do after basal insulin is much more complex. This review builds upon an earlier article in this journal, “Insulin for type 2 diabetes: How and when to get started,”³ by explaining 3 strategies to consider when basal insulin alone isn't enough.

3 main strategies for intensifying treatment

Basal insulin is indicated for patients who have glucose toxicity and persistently elevated hemoglobin A1c (HbA1c) despite using 2 or more oral agents, or for those who have not achieved glucose goals one year into treatment.^3,4 ADA/EASD recommends initiating a weight-based approach for basal insulin therapy based on initial HbA1c levels >7% or >8%.⁴ Instructing and encouraging patients to titrate their own insulin dose based on fasting glucose readings provides greater and faster glucose control.^1,2

Despite these attempts, some patients will not reach their glucose goals with basal insulin. When intensifying treatment beyond basal insulin therapy, patient preference, cost-effectiveness, safety, tolerability, glycemic efficacy, risk of hypoglycemia, effects on cardiovascular risk factors, and other non-glycemic effects should be considered in the shared decision-making process. There are 3 main strategies for intensifying treatment:
1. Basal plus incretin therapy. Add a newer injectable agent such as a glucagon-like peptide 1 receptor agonist (GLP-1RA).
2. Basal plus one strategy. Add prandial insulin prior to the largest meal of the day.
3. Basal-bolus combination. Add insulin prior to all meals.

TABLE 1^5-8 provides details of several studies that have documented the efficacy of these 3 strategies.

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Monitoring blood glucose to guide the way
Blood glucose monitoring using either a 7-point glucose monitoring technique or staggered glucose checks should guide insulin intensification. A 7-point glucose profile includes pre-meal and post-meal readings for 3 meals a day and an additional bedtime reading.⁹ This is typically performed for 3 to 7 days prior to an appointment and provides an estimate of a typical full day’s glucose pattern.

Staggered monitoring includes a pair of glucose checks taken immediately before and typically 90 minutes after a meal. This is assigned to a different meal each day in order to obtain the same information as is achieved with 7-point monitoring, but with fewer checks on any given day. It may take up to 2 to 3 weeks to gather the necessary information using the staggered monitoring technique.

In order to optimize insulin strategies for tighter glycemic control, it is important to review blood glucose logs at each office visit with either of the above techniques.

Basal plus incretin therapy

GLP-1RAs are subcutaneously administered injectable incretin agents. They mimic the action of endogenous GLP-1 hormones, which are normally secreted in response to meals by the cells of the small intestine.¹⁰ GLP-1 stimulates glucose-dependent insulin secretion, suppresses postprandial glucagon release from pancreatic alpha cells, signals satiety, and slows gastric emptying.¹⁰ In other words, GLP-1 appears to be a physiologic regulator of appetite and food intake. GLP-1 is rapidly metabolized and inactivated by dipeptidyl peptidase-4 (DPP-4) enzymes.¹⁰ The amplification of insulin secretion elicited by hormones secreted from the gastrointestinal (GI) tract is called the “incretin effect.”¹⁰ Obesity, insulin resistance, and type 2 diabetes greatly reduce the incretin effect.¹⁰

Insulin intensification should be guided by glucose monitoring using the 7-point technique or staggered glucose checks.

GLP-1RAs mimic the incretin effect and are not degraded by endogenous DPP-4 enzymes.¹⁰ They provide a pharmacologic level of GLP-1 activity, including beneficial glucose effects (via insulin secretion and glucagon suppression), but they also increase GI adverse effects, such as nausea and vomiting.^11-15 Further, they can suppress appetite and contribute to weight loss.^11-15