Glucose Control Therapy Research


The JDRF Glucose Control Therapy Initiative is taking a multi-pronged approach based on the unique unmet clinical needs of patients with type 1 diabetes (T1D), developing an understanding of the mechanisms and properties of each product or pathway, and a commitment to accelerate clinical development and application for T1D products to provide in the short-term a series of incremental benefits to patients. 

JDRF intends to explore potentially transformative approaches based on new treatment paradigms. Seminal studies of novel insulins with improved properties, unique formulations mimicking normal delivery, or creative ways of packaging insulin in biodegradable and safe glucose responsive complexes raises the possibility of discovering and developing a glucose-responsive insulin (GRI) or a liver-targeted insulin that would provide normal blood glucose control similar to an intact beta cell. 

The JDRF strategy is to focus on areas that may allow us to achieve a more automated closed loop system or when used in standard therapy may allow for improved diabetes control.

Ultra-fast insulin:

If successful, ultra-fast insulin could improve quality of life and decrease the risk of acute and chronic complications in persons with T1D (and possibly in those with T2D) caused by recurrent glycemic extremes and limited time spent in the euglycemic range. Ultra-fast insulin may also decrease or eliminate the need for pre-meal insulin boluses, which can predispose a person to dangerous extremes of glycemia when the amount of anticipated carbohydrate intake is (frequently) erroneously estimated even in the most adherent and knowledgeable of patients. Most importantly, improved insulin will enable the development of fully automated closed-loop systems, during which insulin delivery rate is automatically determined and administered with minimal human intervention/error.

Improved Delivery:

Currently, insulin infusion sets deliver insulin subcutaneously (SC) and have a short duration of use (~3 days). Additionally, they have a propensity to have interruptions in insulin delivery due to cannula kinking and occlusion (which, while clinically significant, are not detected by today’s insulin pumps). Thus, improved insulin delivery is a goal within the JDRF program.

Glucose-responsive Insulin:

Most insulin treatments are pre-programmed to release insulin at controlled rates, unlike the normal physiological mechanism of beta cells. Seminal studies in recent years have discovered creative ways of ‘packaging’ insulin in biodegradable and safe glucose-responsive complexes that closely mimic the endogenous machinery yet escape instantaneous proteolytic cleavage. JDRF intends to fund research that will test the hypotheses and establish proof of concept of some of these novel drugs, also known as glucose-responsive insulins (GRI). This area of research in this initiative has perhaps the most promise in offering tight glucose control, prevention of complications and substantial improvement in quality of life by avoiding frequent glucose measurements (via finger sticks or CGMs) and less frequent insulin dosing. In its truest form, the glucose-responsive insulin can ‘replace’ a fully close-loop automated AP. If proof of concept can be achieved, the challenge will then be in the timeframe required for full commercial development and regulatory approval.

JDRF has launched its first Grand Challenge Prize to spur innovation toward the discovery and development of a glucose-responsive insulin drug with transformative potential to treat insulin-dependent diabetes. With the initial $100,000 Challenge prize, JDRF’s ultimate goal is to discover a glucose-responsive insulin drug that would work only when the body needs it. Glucose-responsive insulin would deliver the precise amount of insulin needed in response to circulating glucose levels to control and maintain normal blood glucose levels throughout a daily routine with once-daily or less frequent dosing in people with diabetes. The Challenge is open to the public and more details can be found at the Challenge website.

Hormones beyond insulin:

The physiology of glucose homeostasis is complex, and insulin only corrects part of the pathophysiology of T1D. Additional hormones are now being recognized as playing a vital role in glucose regulation. These include amylin, glucagon-like peptide-1 (GLP-1), glucagon, leptin and others, some of which complement while others synergize with the actions of insulin. New remedies comprising a composite of two or more of these hormones can potentially provide substantial improvements in the treatment, care and hence pathology of T1D. This can be elicited by the additive mechanisms of the actions of multiple hormones over insulin monotherapy, and might protect patients from adverse manifestations of excessive insulin dosing by lowering their insulin requirements. JDRF will test the proof of concept and establish the pharmacological archetype of achieving better than current glycemic control by dosing one or more of these hormones in addition to insulin. This is viewed as a shorter term deliverable than some of the other initiatives. These efforts will then be extended to the closed loop AP system to offer maximum benefit from an evolved product

Novel Therapies:

Several marketed drugs and candidates now in advanced clinical development have shown remarkable efficacy in ameliorating the exacerbating conditions arising out of insulin resistance in patients with T2D. JDRF intends to evaluate the benefits these drugs may provide to patients with T1D in pilot clinical studies so that patients and physicians could leverage their use. This could set the stage for delivery of novel treatment paradigms in a relatively short timeframe and with minimal expenditure of resources.

Lets turn type one into type none