Beyond insulin: ‘Multiple strategies’ needed to improve outcomes in type 1 diabetes
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Treatments for type 1 diabetes must be tailored to the heterogeneity of disease physiology among patients, moving beyond population-based HbA1c measures to individualized glycemic time in targets, according to a speaker.
Data from T1D Exchange show fewer than 30% of people with type 1 diabetes meet recommended HbA1c targets and many now have a BMI in the overweight or obese range, whereas people from underrepresented groups are often not using recommended diabetes devices that can help achieve treatment goals, Michelle Van Name, MD, assistant professor of pediatrics (endocrinology) at Yale University School of Medicine, said during a presentation at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
CVD risk remains very high in type 1 diabetes; development of type 1 diabetes before age 10 years is associated with a loss of 17.7 life-years for women and 14.2 life-years for men compared with matched controls, Van Name said.
“Our current strategies are not adequate,” Van Name said. “There are different drivers of this. Socially marginalized populations have less technology use. The more technology use, the better your HbA1c. We need to think about that more and apply that to adjunctive medication use.”
Consider, treat other targets
In treating type 1 diabetes, clinicians should consider glycemic targets such as time spent in the recommend glucose range, time spent below and above that range, as well as weight reduction in people with an elevated BMI, equitable access to technology and medications and minimizing complications such as CV risk, Van Name said.
“But we are trying to do all of those things with only two approved medications in the United States, and that is insulin and pramlintide,” Van Name said. “That is in stark contrast to the options that we have to tailor our treatments to adults with type 2 diabetes.”
Clinicians tend to have an “insulin-centric” view of type 1 diabetes, when the true pathophysiology is not enough insulin along with an excess of glucagon, Van Name said.
Data show people with type 1 diabetes have dysregulated glucagon secretion in response to a mixed meal tolerance test compared with those without diabetes. Pramlintide, a synthetic form of amylin, helps to lower both glucose and glucagon levels when taken before a meal with insulin when compared with placebo, Van Name said. Large randomized controlled trials of pramlintide also show it is associated with reductions in HbA1c and weight loss, though adverse events can include mild nausea, decreased appetite and severe hypoglycemia.
Options on the horizon
Research for adjunctive, oral pharmacotherapies to treat type 1 diabetes has been limited by hypoglycemia and diabetic ketoacidosis (DKA); however, agents approved for type 2 diabetes are available that can mitigate postprandial hyperglycemia and may be useful in type 1 diabetes, Van Name said.
GLP-1 receptor agonists, currently approved for use in type 2 diabetes, could potentially improve HbA1c, body weight and lower insulin dose in type 1 diabetes, Van Name said.
SGLT2 inhibitors decrease renal glucose reabsorption and do not independently improve insulin response; however, data suggest low-dose empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) could improve HbA1c in type 1 diabetes, with or without hybrid closed loop automated insulin delivery. The FDA has so far declined to approve SGLT2 inhibitors for people with type 1 diabetes due to concerns about DKA; however, continuous ketone monitors currently in development may soon allow for their use, Van Name said.
A hepatoselective glucokinase activator, TPP399 (vTv Therapeutics), added to optimized insulin therapy, has also been shown to reduce HbA1c among adults with type 1 diabetes during a 12-week trial without increasing hypoglycemia risk, Van Name said.
Emergency glucagon treatments have also markedly improved, Van Name said. Instead of complicated kits that require reconstituting powdered glucagon, new, prefilled options allow for liquid glucagon formulations that are stable at room temperature for treatment of severe episodes of hypoglycemia.
“We need development of multiple strategies to target glycemia, glycemic excursions, hypoglycemia and insulin dose that can be tailored to the heterogeneous physiology in type 1 and the preference of the person with type 1,” Van Name said. “We also need further development of continuous ketone meters to enhance safety of adjunctive agents that lower insulin dosing. That has been one of the major problems with moving these drugs forward — the risk for ketosis and DKA. Once we have that on the market, that can help us advance these agents.”
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Van Name M. Session 18: Contemporary Issues in Diabetes. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 1-3, 2022; Universal City, California (hybrid meeting).
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