Incretins comprise two main classes of drugs that work by similar mechanisms. They include glucagon-like peptide type 1 receptor agonists (GLP-1) and dipeptidyl peptidase inhibitors (DPP-IV). There are several approved drugs currently being used effectively for the treatment of type 2 diabetes. These drugs increase the secretion of insulin from pancreatic beta cells, suppress the effects of glucagon, delay gastric emptying, reduce the amount of insulin required to maintain normal glucose levels, and work in a glucose-responsive manner thus reducing the incidence of hypoglycemia. Some of them have additional beneficial effects, such as weight loss, sensitization to the actions of insulin, and other effects. None of them have any serious side effect profiles as evidenced by their successful presence in the diabetes market since 2006.
An increasing body of evidence in the clinical literature suggests that these drugs can be effective for the treatment of type 1 diabetes in several ways, including but not limited to, suppressing the actions of glucagon, decreasing post-meal glucose levels, facilitating tighter blood sugar control, eliciting overall metabolic balance, reducing the total daily dose of insulin – without increasing the incidence or severity of hypoglycemia. And in some cases, they induce weight loss or are weight neutral, as opposed to the weight promoting effects of insulin. Taken together, Incretins are emerging as novel and promising treatments for T1D.
In this specific study, Dr. Urd Kielgats and colleagues demonstrate that the use of Exendin (GLP-1) provides better blood sugar control in all T1D individuals regardless of amount of residual beta cell function. They further show that the main mechanisms by which such blood sugar control is achieved include the suppression of glucagon levels, reduction in post-meal blood sugar excursions, and decrease in gastric emptying, without causing any increased hypoglycemia.
Antidiabetic Actions of Endogenous and Exogenous GLP-1 in Type 1 Diabetic Patients With and Without Residual Beta-Cell Function, Diabetes. 2011, 60:1599-1607
Ramifications for Individuals with Type 1 Diabetes:
Achieving tight blood sugar control, preventing/reducing long term complications and avoiding hypoglycemia are hallmarks of T1D treatment. Despite the advent and advances in insulins, today’s treatments remain challenging and high and low blood sugar remain a daily challenge. Two main reasons for a failure to achieve the above are lack of insulins that mimic normal pancreatic insulin secretion and action patterns, and the use of insulin-only therapy that do not address other abnormal hormonal levels seen in all individuals with T1D.
Incorporating additional drugs into the treatment regimen can not only provide better blood sugar control but also substantially increase the quality of life of individuals living with this difficult disease. Incretins could help reduce the disease burden at many levels as discussed earlier, and these can be made available for T1D individuals in a relatively shorter timeframe by repositioning the T2D drugs.
JDRF did not directly fund this study but is actively pursuing this important class of drugs to design a road map for their evaluation in necessary clinical studies, and ultimately work toward their approval and adoption as a bona fide T1D treatment.