Beyond Insulin
Patients with Type 1 diabetes rely on insulin, but other medications are increasingly prescribed to help stabilize blood sugar levels, as well as secondary symptoms such as hypoglycemia. This journal scan will discuss the most recent literature on the efficacy and administration of supplemental treatments for Type 1 and 2 diabetes.
May 2021
Volume 10, Issue 2

Chapter 4: Inhaled Insulin

Concerns and future promise

Clinical Drug Investigations. 2020;10:973-983

Several years ago the use of inhaled insulin faltered, even though it was projected to be a great success. While offering a needle-free insulin delivery, it was only for prandial insulin use. Diabetics on long-acting or basal insulin still required injections, while insurance obstacles also put it out of many patients' price range, with higher copays or no coverage at all as a non-preferred insulin brand. That being said, it is likely that the idea of inhaled insulin was simply ahead of its time.

Inhaled insulin is used in a similar fashion as fast-acting prandial insulin injections. It is a powdered insulin inhaled through the mouth and into the lungs where it is absorbed across the alveolar epithelium. It comes in fixed doses, usually 4, 8 and 12 units, but these units are not equivalent to units of injectable insulin. In the transition from injectable bolus insulin to inhaled insulin, different formulations are used. For example, 1 unit of injectable insulin may be equivalent to 1.5-2.5 units of inhaled insulin.

Patients with diabetes typically use the inhaled insulin 15 minutes or so before meals. During heavy meals, inhaled insulin can be used for multiple dosing just as its injectable counterpart. Inhaled insulin, however, is faster and shorter acting than bolus insulin. The expediency is a big advantage for inhaled insulin. In addition, it gives patients flexibility when carrying small capsules of insulin in a pocket or purse.

Efficacy of Inhaled Insulin in Clinical Trials

Studies with both Type 1 and Type 2 diabetics found that inhaled insulin was similar to injected insulin in lowering A1C levels, and may even reduce the number of hypoglycemic events. A recent study found that inhaled insulin is even effective in children as young as 6 years old. Insulin-related side effects were similar between both types of meal-time insulin therapies, with the exception of coughing, which was substantially more frequent in the inhaled insulin groups.

In a collaborative study based out of the Barbara Davis Center for Diabetes at the University of Colorado in Denver, inhaled insulin was pitted against injected insulin to control prandial glucose levels. It was referred to as the STAT study in reference the medical term stat or statim, because of the rapid action of inhaled insulin compared to injected bolus insulin. Randomly assigned participants engaged in continuous glucose monitoring for four weeks.

As seen in other recent studies, both groups had similar A1C levels. A bit over 50% of participants’ time was spent in range (TIR, 70-180 mg/dL) and approximately 40% of time in the hyperglycemic range (>180 mg/dL). Those in the inhaled insulin group had smaller post-prandial glucose excursions, with significantly fewer falling into moderate or severe hypoglycemia (<60 mg/dL and <50 mg/dL). In other words, the STAT study suggests that inhaled insulin may give diabetics an easier pathway to glycemic control.

Lung Function: A Treatment-Emergent Adverse Event?

As with any inhaled medication, patients can be concerned with how it affects their lung function. The STAT study measured participants forced expiratory volume in one second (FEV1) and did not find evidence of reduced lung function during the short period of their study. A 16-week study also found no differences in FEV1 measures between inhaled and injected insulin users. 24-week data found small changes. This meta-analysis pooled data across 13 clinical trials to investigate pulmonary adverse events in Type 1 and Type 2 diabetics treated with an insulin inhaler compared to an insulin-free inhaler or standard treatment of care not involving inhaled diabetic therapies.

In the 24-week data, coughing was the most common side effect, affecting more than 1 in 5 participants in both groups using inhalers. The cough typically emerged within 10 minutes of using the device. Throat irritation was also reported by many in the inhaled insulin group compared to the standard care group. There were no other significant differences in respiratory adverse events. For example, all groups had similar cases of bronchitis and upper-respiratory tract infections. In lung function tests, patients using inhaled insulin experienced a small reduction in FEV1 (~0.07-0.13 L) and forced vital capacity (FVC; ~ 0.12 L) at 24 weeks of treatment. During a four week washout period, though, FEV1 and FVC measures returned to control values.

Even though there were measurable changes in lung function, it is important to remember that they were small, reversible and most likely clinically non-significant. Otherwise healthy patients with either Type 1 or Type 2 diabetes can use inhaled insulin without concern for lung function, which should not be seen as a barrier to inhaled insulin. In patients who already have an underlying lung problem such as asthma or COPD, it would not be recommended, as it would also not be recommended for smokers. Beyond these obvious limitations, Kobos et al. found that chronic smokers had an increased absorption of insulin when inhaled, but that sensitivity to insulin was reduced. This effect was reversible after four weeks of smoking abstinence.

Inhaled Insulin Found Effective for Glucose Control

Inhaled insulin is as effective as injected bolus insulin for prandial glycemic control in both Type 1 and Type 2 diabetics, and is more effective in reducing hypoglycemia. Patients may experience some coughing or throat irritation when using the inhaler, but studies suggest that lung function remains clinically unaltered.

This chapter discussed inhaled insulin for treating diabetes, which is inhaled orally. Nasal inhalation of insulin is currently under investigation for the treatment of Alzheimer’s disease and other cognitive degenerative disorders. Nasal administration bypasses the blood-brain barrier, which would normally prevent the passage of insulin. As there are theories surrounding the connection between Alzheimer’s disease and diabetes, it is likely that we will see more studies on both types of inhaled insulin in the future.


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