I have long been frustrated that ADA Guidelines still have insulin therapy as the last step in its Diabetes Standards of Care, despite empirical evidence via numerous studies that nearly half the patients diagnosed with early Type 2 diabetes could be cured by early intensive insulin treatment.

By cured, I mean complete drug-free remission of the disease.

Model Clinical Research (MCR) Study

In the MCR clinical study investigators are seeking to demonstrate that the addition of mealtime Afrezza inhaled insulin (aka Technosphere Insulin) can significantly lower HbA1c within 3 months in uncontrolled type 2 diabetes patients initially having HbA1c of 7.5 or higher, despite at least 6 months of prior therapy with diabetes medications.2

The trial protocol instructs patients to follow a weekly Treat-to-Target BG Testing Regimen and make Afrezza dose changes according to an Afrezza Titration Algorithm.

MannKind Corporation will be presenting data from its latest clinical trial, entitled “Initiating Mealtime Ultra-Rapid-Acting Insulin (Afrezza) in Uncontrolled Type 2 Diabetes Patients” in June at the American Diabetes Association 79th Scientific Sessions in San Francisco. Although the remission of diabetes is not the primary goal of this study, the results could provide further clinical evidence that validates the effectiveness of STII for early diabetes treatment using the current HbA1c standard.

At the 2018 ADA, MannKind Corporation the results of a novel study conducted by the Barbara Davis Center for Diabetes University of Colorado Denver, Afrezza Inhaled Insulin (human) testing focused on treatment for Type 1 diabetes with significant results:

• Significantly increased glucose TIR by approximately 2 hours per day
• Significantly reduced time in hyperglycemia > 180 mg/dL
• Significantly lower PPGE 1 to 4 hours post-meal
• Significant reductions in glucose as early as 60 minutes following Afrezza dose
• Less hypoglycemia (as measured by time spent less than 60 mg/dL); notably, the average Afrezza-treated individual spent approximately 3 minutes per day with blood glucose values less than 50 mg/dL compared to approximately 12 minutes per day for aspart-treated individuals

At this year’s ADA Scientific Sessions, MannKind will be demonstrating the benefits of its ultra-rapid-acting Afrezza inhaled insulin for the treatment of early Type 2 diabetes.

Validity of Early Insulin Treatment

The list of studies validating short-term intensive insulin therapy for newly-diagnosed Type 2 diabetes is growing.  One of the more impressive meta-analyses I have seen published involved 839 participants in China treated with Short-Term Intensive Insulin (STII) therapy. The results were significant.

In the pooled data, the proportion of patients in drug‐free remission was 66.2% [292/441] at 3 months, 58.9% [222/377] at 6 months, 46.3% [229/495] at 12 months, and 42.1% [53/126] at 24 months. These rates of remission are far greater than those that can be achieved with any other currently available medical therapy for diabetes. Source: https://onlinelibrary.wiley.com/doi/full/10.1002/dmrr.2603

Personal Interest

My personal interest in this subject is two-fold. I have friends and relatives who have died from diabetes-related complications and who were forced to endure a poor quality of life due to physical, emotional and financial repercussions of diabetes.

Secondly, I am an ordained minister and see it as part of my civic duty to bring this issue to light.

The current Diabetes Standard of Care still advocates insulin as one of the last options for treating diabetes. Unfortunately, waiting until oral and other treatment progressions published in the ADA Diabetes Standard of Care fail may simply be too late for stressed insulin-producing beta-cells to be repaired. By the time doctors prescribe insulin, the pancreas may be damaged beyond repair.

Why STII is Better

In the early stages of Type 2 diabetes, insulin resistance and other factors often cause the pancreas to become over-stressed and unable to keep up with the body’s demand for insulin. In layman’s terms, the beta cells in the pancreas begin to wear out.

Early treatment of diabetes with oral medications, such as Metformin, does not assist the pancreas to improve its ability to produce sufficient levels of insulin. Early intensive insulin therapy, on the other hand, can provide a respite to the over-stressed pancreas by providing much-needed insulin and thus enabling the pancreas to recuperate and build new insulin-producing beta cells at a rate that will meet the body’s demand while, at the same time, lowering insulin resistance.

ADA Guidelines Need to Change

The MCR Afrezza study does not necessarily have a goal of remission so much as a significant reduction in HbA1c levels because that is the current standard by which diabetes treatments are currently judged.  

For decades, studies have conclusively demonstrated that early intensive insulin therapy administered to newly-diagnosed Type 2 diabetes patients can result in remission of the disease.  In a major study published in The Lancet in Sept-20131, researchers noted that “when implemented early in the course of type 2 diabetes mellitus, treatment with intensive insulin therapy for 2-3 weeks can induce a glycaemic remission, whereby patients are able to maintain normoglycaemia without any anti-diabetic medication.

Despite growing clinical evidence that early initiation of short-term intensive insulin therapy (STII) has repeatedly demonstrated significant results, including remission of diabetes, the American Diabetes Association still has insulin therapy as the last step in its Diabetes Standards of Care.

The ADA Guidelines need to change.

Foregoing early short-term intensive insulin therapy for early treatment of Type 2 diabetes mellitus in favor of cheaper oral medications may result in continuous deterioration of the pancreas to the point where the insulin-producing pancreatic beta cells are no longer repairable, leaving the patient sentenced to a difficult life of continuously fighting diabetes. It’s a fight that can be won with a 1st Round knockout and a 50% proven rate of drug-free remission of the disease is significant.

Footnotes:

1. Article “Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis” published in The Lancet, Diabetes & Endocrinology – Volume 1, Issue 1, September 2013, Pages 28-34
2. Initiating Mealtime Ultra-Rapid-Acting Insulin (Afrezza) in Uncontrolled Type 2 Diabetes Patients — http://clinicaltrials.gov/ct2/show/NCT03324776?term=mannkind&recrs=abdfg&rank=3