CE / CME
ABIM MOC: maximum of 0.75 Medical Knowledge MOC point
Physician Assistants/Physician Associates: 0.75 AAPA Category 1 CME credit
Nurses: 0.75 Nursing contact hour
Physicians: maximum of 0.75 AMA PRA Category 1 Credit™
Released: October 26, 2023
Expiration: October 25, 2024
Discussion
In the United States, more than 37 million people (or 11.3% of the population) have been diagnosed with diabetes.1 Worldwide, it is projected that 783 million people will have diabetes by 2045, with certain populations at higher risk than others.2 Primary care physicians are estimated to deliver 90% of the care to individuals with type 2 diabetes and have an increasing role in providing diabetes care.3
Diabetes is a progressive disease involving not only insulin resistance, but also a decrease in β-cell function that can lead to the need for insulin therapy. Diabetes is of clinical importance because of long-term complications associated with the condition, including small-vessel complications such as diabetic retinopathy and diabetic nephropathy and large vessel complications such as stroke and cardiovascular disease. Research has shown that both microvascular and macrovascular complications are associated with higher glycemic levels, underscoring the importance of glycemic control in improving outcomes for patients with type 2 diabetes.4
Over the past 2 decades, overall glycemic control has not improved. Approximately one half the patient population does not achieve a glycemic target of <7.0%,5 the ADA-recommended goal for most nonpregnant adults,6 and approximately 25% of patients do not achieve an A1C of <8.0%.7 In the same time period, the use of insulin therapy has increased proportionately to approximately 25% of patients.8 Therefore, despite the emergence of new treatments for diabetes, there is an unmet need for glycemic control that can potentially be addressed by increased use of insulin therapy.
Historically, physicians have followed a treat-to-failure approach for managing diabetes, initially starting metformin and, as glycemic levels reach a certain threshold, adding additional agents or insulin therapy. This approach typically results in a delay of 6-7 years after maximization of oral therapy before beginning insulin therapy.9 Delay in insulin therapy initiation and lack of adequate titration could exacerbate poor glycemic control in some individuals.10
There are various reasons both healthcare professionals and patients can be reluctant to initiate insulin therapy.11 Patients worry about the impact of insulin therapy on their social life. They have doubts about efficacy and concerns about the safety of insulin. They do not feel confident titrating the medication and worry about forgetting doses. Healthcare professionals sometimes think titration is too complex for the patient and that patients lack support and resources for initiating insulin therapy. Concerns about hypoglycemia, weight gain, the need for injections and blood tests, and adherence often are shared by both patients and healthcare professionals. However, providing proper education to patients and giving them control over their insulin therapy can help reduce reluctance and delays in initiating treatment.
Insulin has an important role in the ADA-recommended treatment algorithm for type 2 diabetes. The ADA recommends that GLP 1 RAs be considered as the first injectable in most patients who are not achieving A1C targets with oral agents.12 In patients with severe hyperglycemia or suspected type 1 diabetes, immediate initiation of insulin should be considered. For patients receiving a GLP 1 RA who do not achieve their A1C target, basal insulin is an appropriate next step.12 For example, in the case challenge, the patient tolerated semaglutide well but was still above her recommended A1C level; therefore, ADA guidelines would advise addition of basal insulin. The ADA recommends starting insulin at 10 units or 0.1 unit/kg/day and then adjusting by 10% to 15% or 2 4 units once or twice weekly to reach the FBG target. If patients do not achieve their treatment target even after titration of basal insulin, then prandial insulin should be considered. If additional stepwise injections of prandial insulin are insufficient to achieve treatment goals, a further step is a bolus insulin regimen or a mixed regimen.12
Other indications for insulin therapy are unacceptable adverse events to other medications and presence of advanced hepatic or renal disease. In addition, for patients with special considerations—such as pregnancy, infection, steroid use, and those in the hospital setting—insulin is appropriate.13
A wide selection of basal insulin is available. Neutral protamine Hagedorn (NPH) insulin has an onset within 1-2 hours and a peak of 4 12 hours, which makes it useful twice daily as a basal insulin. However, glycemic variability has been associated with NPH, and the risk for hypoglycemia is high.14 More recent insulins are longer acting, including detemir and glargine. Ultra-long–acting insulins, such as glargine U 300 and degludec, essentially have no peak, have a duration of action >24 hours, and have the least glycemic variability and consequently lowest rates of hypoglycemia.15
With the various treatment options available, success with insulin therapy requires shared decision-making. The ADA provides a detailed decision cycle for person-centered glycemic management in type 2 diabetes.16 Healthcare professionals can provide guidance based on the patient’s goals and concerns. For example, patients concerned about injecting insulin in public might be prescribed a long-acting basal insulin that could be injected before bedtime every night. This conversation should be followed up at subsequent visits, and patients should be asked if they have any new or persistent concerns. Adherence to their insulin regimen requires patients to understand the benefits and risks of their selected therapy.
Indeed, nonadherence is a common problem with insulin therapy.17 Approximately 20% to 50% of patients report missing an insulin dose at least once per month.18 Nonadherence is particularly problematic in diabetes treatment, as it can result in immediate hyperglycemia. Common reasons for nonadherence include travel, busy work schedules, skipped meals, and avoidance of hypoglycemia. Education programs to help improve adherence are critically important. These educational programs give people tangible tools to help dose their insulin, which can improve treatment adherence, raise the chances of achieving therapeutic targets, and lower rates of chronic complications associated with poor glycemic control.
The ADA also recommends glycemic assessment by CGM, particularly for patients with type 1 diabetes, but also for patients with type 2 diabetes on insulin therapy.6,19 In the case challenge, the patient reported periodic episodes of hypoglycemic symptoms while titrating glargine but could not provide measurements on her blood glucose levels. This is a situation where CGM can assist in guiding treatment. CGM allows for interval blood glucose measurements that can more accurately reflect the peaks and valleys of blood glucose in the course of the day. These monitors and connected apps also provide alerts and can inform patients and healthcare professionals about glucose trends. Some CGM devices measure in real time and store data on glucose levels continuously without any prompting; other CGM devices can send data directly to the healthcare professional and provide 7-14 days of measurements to review when assessing the efficacy of a particular treatment plan. CGM data can enable healthcare professionals to modify or customize treatment plans and address concerns about missed doses or meals that might appear on reports as abnormal hyper- or hypoglycemic periods.
The ADA and the American Association of Clinical Endocrinology suggest a time-in-range goal of 70% for nonpregnant persons, with a time-below-range goal of <4%.6,20 Data have shown these time-in-range goals correspond to an A1C of approximately 7.0%.6,21 The time-in-range goal can be lower for older and high-risk patients with type 2 diabetes but should be higher for patients who are pregnant and have gestational diabetes. Glycemic level goals and A1C targets may need to be adjusted based on an individual’s medical history, needs, and treatment response.
Finally, an emerging new treatment is weekly basal insulin, which is currently in phase III trials and has thus far been shown to be effective without increased risk of hypoglycemia.22 Weekly basal insulin offers promising benefits to adherence and may conveniently complement cotreatment with once-weekly GLP-1 RAs. These new agents likely will require consensus regarding initial insulin dose, titration methods, and strategies for switching from one insulin to another. Nevertheless, weekly insulin is an encouraging development that may reduce treatment burden and improve adherence and outcomes.
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