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Not Always a Last Resort: The Evidence for Basal Insulin
Not Always a Last Resort: The Evidence for Basal Insulin

Released: July 17, 2023

Richard E. Pratley
Richard E. Pratley, MD
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Key Takeaways
  • Despite the availability of many new treatments for type 2 diabetes, many people with diabetes do not achieve glycemic goals.
  • Long-acting basal insulin is a good option for patients who may not respond well to oral treatments or who cannot afford more expensive therapies.
  • Once-weekly basal insulins are in development and could offer more convenient treatment options and improved adherence. 

This year marks the 100th anniversary of the first use of insulin to treat patients with diabetes, and much has changed in the treatment of diabetes since that time. For many years, insulin was our only therapeutic option for treating diabetes, but in the past 2 decades, we have seen a veritable explosion of new treatments—particularly the development of glucagon-like peptide-1 receptor agonists (GLP‑1 RAs). These are highly effective drugs that are associated with weight loss and, in some cases, cardiovascular benefit. Consequently, our treatment algorithms have shifted, and the American Diabetes Association now recommends GLP‑1 RAs as the first injectable treatment option when oral medications do not adequately control the disease.

With all these new options, is there still a role for basal insulin in the treatment of diabetes? I think the answer is a resounding yes. In parallel with the development of new classes of drugs for the treatment of type 2 diabetes, there have been further refinements of insulin therapy in the past few years. We now have long‑acting basal insulins that are very effective at controlling fasting glucose levels and reducing variability with a low predilection for causing hypoglycemia. Currently in the United States, almost one half of patients with diabetes are not achieving an A1C target of less than 7%, despite the availability of more than 12 classes of medications to treat type 2 diabetes. Therefore, it is clear that insulin therapy is still needed. Because diabetes is a progressive disease and part of the progression is characterized, at least in part, by a loss of β-cell function, people over time become less and less able to secrete enough insulin to control their blood glucose level. These are the patients for whom basal insulin is a great treatment.

A major development in the past 5 years is the recognition that type 2 diabetes is not a monolithic disease. In fact, there are at least 5 subtypes of diabetes, one of which is characterized by insulin deficiency. In many ways, this subtype is more like type 1 diabetes, although there is a lack of evidence for autoimmune destruction of beta-cells. These patients may not do as well with metformin, they typically have higher A1C levels and are more prone to complications such as retinopathy. Such patients represent another group of patients who might benefit from basal insulin, as they may not have had success with multiple oral medications and may not have achieved their therapeutic target. Other patients with more typical type 2 diabetes may have tried a GLP‑1 RA and were either unable to tolerate this option or unable to achieve glycemic control with it. Similarly, some patients who have severe and potentially symptomatic hyperglycemia on presentation would benefit most from insulin treatment to rapidly restore their metabolic status from a catabolic state. Finally, for hospitalized patients and patients with certain conditions (eg, hepatic insufficiency and severe chronic kidney disease), insulin therapy, including basal insulin, usually is recommended.

Recently, there has been considerable discussion about the cost of insulin treatment. Insulin is still an excellent choice for people who are constrained by cost because these individuals can buy basal insulin—for example, NPH—at very reasonable rates. In the past few years, there have been developments in creating biosimilar insulins, and their availability is beginning to decrease the overall cost of obtaining basal insulins. Initiatives also are in place, such as for patients with Medicare, to limit the out-of-pocket cost of insulin to approximately $35 per month. So, unlike some of the newer medications—which are very expensive—insulin represents an affordable and effective treatment option for patients who have cost constraints.

Newer insulin treatment options for diabetes that are dosed weekly instead of daily are in development. We already have GLP‑1 RAs that are dosed once weekly, and they offer more convenient treatment options for patients with diabetes. Weekly insulins still are being evaluated in trials, but data so far appear to show that weekly insulins are effective and do not have a higher risk for hypoglycemia, as might be expected from less-frequent dosing. Not only do these weekly insulins offer more convenient dosing, but they also might improve adherence. If a patient needs to take medication only once weekly, the chances of missing 1-2 days of treatment—which can occur when using daily insulin—could be avoided and result in better long‑term outcomes in glycemic control. Further research is needed in real‑world use, but weekly insulins offer a very promising potential development.

Although basal insulin is not always the drug of first choice for type 2 diabetes, there are many cases in which it is an appropriate choice or may be the preferred therapy. The goal is to use insulin in appropriate patients without delaying the advancement of insulin therapy to help them achieve glycemic control and avoid unnecessary hyperglycemia.

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