When Should Insulin be Started?
Q. Will my patient with type 2 diabetes require insulin?
A. It varies from patient to patient. However, type 2 diabetes is a progressive disease marked by gradual loss of beta cell function and most patients will eventually require insulin therapy.1 This should be viewed as part of the pathophysiology of the disease and not as a failure on the part of the patient or healthcare provider.
Insulin should be discussed early with patients who are beginning to show progression of their diabetes to ease the transition when the time to start insulin therapy arrives. This time should be considered part of a larger conversation between provider and patient, and not seen as a turning point down a path to the many severe complications of diabetes.
Q. Is there a specific hemoglobin A1c (HbA1c) at which insulin must be started?
A. No. Insulin, like all treatments for diabetes, should be started and adjusted to achieve a reasonable goal HbA1c for the patient. The American Diabetes Association (ADA) previously recommended that a patient’s HbA1c not be allowed to exceed 8%, creating an “action point” for escalation of therapy.
However, population studies have shown that the burden of hyperglycemia due to reluctance to start or advance therapy is significant and put patients at risk of earlier complications.2 Newer guidelines recommend advancing therapy to a goal HbA1c, which is individualized to the patient’s needs (under 7% for most patients).3 If a patient’s HbA1c rises above target and does not respond to 2 or more oral hypoglycemic agents,4 changes in their regimen should be made sooner rather than later to prevent unnecessary hyperglycemia.
If insulin is needed to achieve this goal, it should be started right away rather than waiting to see if other treatments will work with more time. Prolonged exposure to hyperglycemia not only increases the rate of development of complications, but also may hasten progression of diabetes due to the direct toxicity of hyperglycemia to beta cells.5 Insulin and some noninsulin therapies, such as glucagon-like peptide-1 (GLP-1) agonists and thiazolidinediones, have protective effects on beta cells—preserving their function both acutely and long-term.6,7
Insulin therapy will often need to be started if the initial fasting plasma glucose is greater than 250 or the HbA1c is greater than 10%.4
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Q. Are there certain circumstances where insulin should be considered sooner?
A. Since most non-insulin treatments for diabetes lower the HbA1c by 0.5% to 1%, patients with a starting HbA1c >9.5% are less likely to achieve an HbA1c at goal with a single agent and initial therapy with 2 agents is reasonable.3
Insulin is unique in that the dose can be increased indefinitely, limited only by development of hypoglycemia. Basal insulin alone or with oral/injectable noninsulin medications is often sufficient. Insulin decreases beta cell stress, thereby enhancing function to increase endogenous insulin stores, which are needed to compensate for postprandial hyperglycemia.5
In some cases, after a period of intensive therapy with insulin and good glucose control, insulin may be replaced with other agents with continued control. On the other hand, some patients with advanced diabetes and beta cell failure may require multiple daily insulin injections at the time of diagnosis or shortly thereafter.
Younger patients who are at risk for long-term cumulative effects of hyperglycemia and gradual beta cell failure may benefit from early insulin therapy to preserve beta cell function and achieve goal HbA1c values more rapidly. For some of these patients, a lower goal A1c of 6.0 to 6.5 may be more appropriate if they are motivated and do not develop hypoglycemia.3
Q. Are there patients who should not receive insulin?
A. The ADA currently recommends choosing a goal HbA1c for the patient based on a number of factors, including patient motivation, risk of hypoglycemia, duration of disease, life expectancy, comorbidities, evidence of complications, and availability of support systems.3 If a patient is unlikely to benefit from aggressive glucose control, a higher goal HbA1c should be used thereby making insulin potentially unnecessary. Because of insulin’s tendency to induce hypoglycemia, any patient who has frequent episodes needs to have their regimen reassessed. This is particularly important if they live alone or have impaired mobility making access to food more difficult should they become hypoglycemic.
Q. What factors should I consider when starting my patient on insulin?
A. Starting insulin, even only once a day, is an involved process. Very few other medications require patients to manually select their own dose, which can initially be intimidating to patients. They should start insulin after a thorough review of injection technique, medication administration, and learning the signs, symptoms, and treatment of hypoglycemia, ideally with instruction by a diabetes educator. This can be helpful to reduce anxiety related to injections and ensure proper technique. Adequate supplies for patients on insulin should also be prescribed including syringes or pen needles, a glucose meter with test strips, lancets, and alcohol swabs.
Q. What new treatments are available or on the horizon?
A. Lifestyle changes and metformin are still considered first-line therapy. A variety of new classes of antidiabetes medications are now available, which provide more options than the traditional stepwise transition from metformin to metformin/sulfonylurea combination therapy to insulin. These new classes include GLP-1 agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT2) inhibitors. Guidelines provide multiple options as to which agent should be added next.8,9 Since each class works through a different mechanism, the effects are largely cumulative. The side effect profiles of the medications and patient preferences should be considered.
Some ultra long-acting formulations of insulin, including insulin degludec and pegylated insulin lispro, are currently under investigation but not yet FDA approved.■
Conor Best, MD, is a clinical fellow in the division of endocrinology, metabolism, and lipid research at Washington University School of Medicine in St Louis, MO.
Kim A. Carmichael, MD, is an associate professor of medicine in the department of internal medicine, division of endocrinology, diabetes, and lipid research at Washington University School of Medicine in St Louis, MO.
References:
1. Jabbour S. Primary care physicians and insulin initiation: multiple barriers, lack of knowledge or both? Int J Clin Pract. 2008;62(6):845-847.
2. Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Diabetes Care. 2004;27(7):1535-1540.
3. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35(6):1364-1379.
4. Wallia A, Molitch ME. Insulin therapy for type 2 diabetes mellitus. JAMA. 2014;
311(22):2315-2325.
5. Turner RC, McCarthy ST, Holman RR. et al. Beta-cell function improved by supplementing basal insulin secretion in mild diabetes. Br Med J. 1976;1(6020):
1252-1254.
6. Bunck MC, Cornér A, Eliasson B, et al. Effects of exenatide on measures of b-cell function after 3 years in metformin treated patients with type 2 diabetes. Diabetes Care. 2011;34(9):2041-2047.
7. Gastaldelli A, Ferrannini E, Miyazaki Y, et al. Thiazolidinediones improve beta-cell function in type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2007;292(3):E871-E883.
8. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Suppl 1):S14-S80.
9. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559.