Children’s endocrinologists are taking a closer look at how GLP-1 can help T1D patients. (Stock photo)
By Charles Buchanan
Over the course of a century, insulin has become the foundation of diabetes treatment, saving countless lives and transforming the fatal disease into a manageable chronic condition. Yet a majority of people with type 1 diabetes (T1D)—80%, according to Giovanna Beauchamp, M.D., a pediatric endocrinologist at Children’s of Alabama and the University of Alabama at Birmingham—still struggles to achieve optimal glycemic control with insulin alone.
GLP-1 receptor agonists, a therapy originally developed for type 2 diabetes (T2D) that has become a popular weight-loss aid, could provide a solution. In the past few years, a growing number of pediatricians and endocrinologists have prescribed GLP-1 along with insulin for T1D and reported promising outcomes. Beauchamp and Ortal Resnick, M.D., a pediatric endocrinology fellow at Children’s, recently published a review of clinical research that details GLP-1’s impact and offers hope that more patients may be able to take charge of their disease.
Weight Control for Diabetes Control
Maintaining a healthy weight and achieving good diabetes control are difficult even with technology such as insulin pumps, continuous glucose monitors, and automated insulin delivery systems—because the challenge is insulin itself, Beauchamp said. The anabolic hormone causes people with T1D to gain weight, setting off an escalating cycle of complications.
In fact, about 60% of people with T1D are considered overweight or obese, Resnick said. “On average, a patient that starts on insulin treatment gains five kilograms in the first five years of treatment. So we know the treatment by itself causes weight gain.”
Overweight and obesity also are increasingly common in people with T1D at the time of diagnosis, which shows that the traditional stereotype of T1D as a disease affecting only lean individuals is not entirely accurate, Resnick explained. Obesity, associated with increased inflammation in the body, may contribute to triggering or accelerating autoimmune processes in people who are genetically predisposed to developing T1D.
That additional weight also increases insulin resistance, which means that patients need more insulin, which leads to more weight gain—and then the loop begins again. Round after round, the stakes get higher, eventually spiraling into obesity that sparks inflammation and further destruction of beta cells. Severe diabetes, threatening damage to the heart, kidneys, eyes, and other organs and tissues throughout the body, can set in early.
GLP-1 therapy provides an off-ramp from the worsening cycle. Formally known as glucagon-like peptide-1 receptor agonists, the medications are based on the body’s natural GLP-1 hormone, which affects insulin secretion and helps us to feel full after we eat. Prescribing them as a therapy efficiently ramps up both processes, as seen in patients with T2D who have benefited from GLP-1’s improved glycemic control and weight loss over the past two decades. In T1D, just as in T2D, GLP-1 curbs the appetite and makes insulin more effective. Eating less leads to weight loss and reduced doses of insulin.
Research Review
For their research review, Beauchamp and Resnick analyzed results from about a dozen clinical trials of GLP-1 in patients with T1D. They compiled evidence about the medication’s effects on weight and HbA1c, an individual’s three-month average amount of blood sugar, among other measures.
Their findings revealed that adding GLP-1 led to consistent weight loss across all the trials, and most participants were able to lower their insulin doses. HbA1c improved around 0.3%, a small number that nevertheless has significant meaning for patients because it indicates better glycemic control, Resnick said. “The fact that they’re losing weight and their total daily insulin is decreased . . . is a big outcome that we think will affect their long-term complications.”
Beauchamp agreed. “The best way that we are going to see improvement in those potential complications is by improving glycemic control and with weight management. By helping with weight loss and consequently decreasing the amount of insulin that our patients will need, the rate of diabetes-related complications should decrease.”
Maintaining Glucose Balance
Naturally, physicians may be wary of reducing insulin because of the chance it could disrupt patients’ glucose balance and push them into hyperglycemia—high blood sugar. Beauchamp and Resnick investigated that potential outcome and found that, in the studies they reviewed, adding GLP-1 and decreasing insulin resulted in fewer instances overall of hyperglycemia and diabetic ketoacidosis, a severe insulin deficiency requiring intensive care. As for hypoglycemia—low blood sugar—the risk exists, but endocrinologists can carefully monitor and manage the balance between the two medications in response to each patient’s weight loss and decreased insulin need, Resnick said. Patients should continue to eat enough for healthy nutrition, and following a balanced diet is essential. Otherwise, “very easily, you can become malnourished if you decrease your appetite and eat only nonnutritional food,” she said.
The most common side effects of GLP-1 that Beauchamp and Resnick identified in their review were nausea and vomiting, the result of the medication slowing the process of gastric emptying. People who experience this are often used to eating big meal portions, Resnick said. Consuming smaller portions and decreasing the meals’ fat content helps reduce nausea and vomiting, as does increasing the dose of GLP-1 at a slower, more gradual pace, she added.
A Treatment for Life?
Another key question on the minds of many physicians: What are the health implications of taking GLP-1 long term? Beauchamp noted that GLP-1 likely would be a lifelong treatment, alongside insulin, because of its benefits in helping patients with T1D control obesity and reduce their risk for related complications. However, she emphasized that researchers currently don’t have enough data to say for sure.
“We need more time, and we need more research,” Beauchamp said. That actually was one of the crucial takeaways from their review of previous work—that more studies are needed. So far, only a few trials have focused on GLP-1 specifically for T1D, and most used an older version that was administered daily, now superseded by a stronger weekly formulation. And no existing study has followed patients early enough in the course of their disease to observe whether the medication can preserve some beta-cell function.
Still, “we have been using GLP-1 for T2D for about 20 years now [and] from what we know . . . it’s pretty safe,” Resnick said. Patients also don’t receive the same amount of GLP-1 forever, she added. Once the initial dose helps them lose weight, patients are prescribed smaller doses to help them maintain their target weight.
Beauchamp hopes that more pediatricians and endocrinologists will become comfortable using GLP-1 for T1D. Personalizing the therapy for each patient is the key to navigating potential challenges, she said. “Those of us who have used it for patients with T1D and obesity, we see wonderful benefits. I think they are all very pleased with those results, which then lead to better diabetes control, [an] overall better outlook in life, and being able to live a healthy and happy life.”
To learn more about the research Beauchamp and Resnick are doing on GLP-1, check out this episode of the Children’s of Alabama PedsCast.