The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has surged among people with type 1 diabetes, largely driven by rising obesity rates in this population1 2. These drugs, originally developed for type 2 diabetes and obesity, offer promising benefits such as weight loss and improved glycemic control but also carry potential risks that are not yet fully understood in type 1 diabetes3 4. As more patients with type 1 diabetes seek these medications, it is crucial to understand their effects, safety concerns, and clinical considerations1 5.
GLP-1 Drugs for Type 1 Diabetes: Rising Use
Type 1 diabetes (T1D) is an autoimmune disease marked by the destruction of pancreatic beta cells, resulting in absolute insulin deficiency and the need for lifelong insulin therapy6 . Historically, individuals with T1D were typically lean, but recent data reveal a growing prevalence of overweight and obesity in this group, reaching up to 38% among adults and 26% among youth7 12. This trend is especially notable among minority populations and is partly attributed to intensive insulin regimens and compensatory behaviors to avoid hypoglycemia, such as increased caloric intake and reduced physical activity8 6.
The increasing obesity burden in T1D has led to a rise in off-label use of GLP-1 receptor agonists, which are FDA-approved for type 2 diabetes and obesity but not for T1D9 1. Real-world data show that prescriptions for GLP-1 RAs among obese individuals with T1D have sharply increased, with up to 33% of severely obese adults and 21% of severely obese youth with T1D receiving these medications between 2020 and 20231 2. The most commonly used GLP-1 RAs in this population include liraglutide, semaglutide, and tirzepatide9 1.
There are different reasons why people want to lose weight. One is that, medically, the weight loss will allow them to be healthier. But depending on the individual, the most powerful reason might be cosmetic19 .
GLP-1 receptor agonists mimic the natural GLP-1 hormone, which is secreted by intestinal cells in response to food intake. They enhance glucose-dependent insulin secretion, suppress glucagon release, slow gastric emptying, and promote satiety, leading to improved glycemic control and weight loss10 11. In type 2 diabetes, these effects also contribute to cardiovascular and renal protection12 10. While these benefits are well documented in type 2 diabetes, their applicability to T1D remains under investigation4 13.
Key points on GLP-1 use in T1D:
- Rising obesity rates in T1D have driven increased GLP-1 RA prescriptions1 2.
- GLP-1 RAs improve satiety and reduce appetite, aiding weight loss11 .
- Liraglutide, semaglutide, and tirzepatide are the primary agents used off-label in T1D9 .
- GLP-1 RAs have proven cardiovascular and renal benefits in type 2 diabetes, but data in T1D are limited12 13.
- More research is needed to clarify long-term safety and efficacy in T1D4 14.
Popular prescription weight-loss drugs called GLP-1 receptor agonists are now frequently used by type 1 diabetes patients, despite limited data on the drugs' safety and effectiveness in this patient population2 .
Potential Dangers for Type 1 Diabetes Patients
While GLP-1 receptor agonists offer promising benefits, their use in T1D carries notable risks that require careful consideration. The primary safety concerns include hypoglycemia (dangerously low blood sugar) and diabetic ketoacidosis (DKA), a serious condition characterized by high blood sugar and ketone accumulation4 102.
GLP-1 RAs potentiate insulin action by enhancing glucose-dependent insulin secretion and suppressing glucagon, which can lead to excessive glucose lowering when combined with insulin therapy10 . This interaction increases the risk of hypoglycemia, especially if insulin doses are not carefully adjusted4 10. Conversely, reducing insulin doses too aggressively during GLP-1 therapy may precipitate hyperglycemia and ketosis, increasing DKA risk4 .
Clinical trials with liraglutide in T1D patients have demonstrated modest reductions in HbA1c (a marker of long-term blood sugar control) and body weight but also reported increased episodes of hypoglycemia and ketotic hyperglycemia4 13. The risk-benefit balance remains uncertain, as these trials often excluded patients with advanced disease or did not focus on those with obesity, who might benefit most4 13.
Additional side effects common to GLP-1 RAs include gastrointestinal symptoms such as nausea, vomiting, diarrhea, and constipation, which can affect adherence15 11. Rare but serious adverse events reported in the broader population include pancreatitis, gastroparesis (delayed stomach emptying), bowel obstruction, gallstones, and bile duct blockage15 11. These risks underscore the need for careful patient selection and monitoring.
A growing concern is the use of compounded (non-FDA-approved) GLP-1 formulations, which lack standardized dosing and quality control. The FDA has issued warnings about compounded semaglutide and tirzepatide products due to reports of dosing errors, adverse events, and counterfeit drugs16 5. These products may lead to severe side effects, including gastrointestinal distress and injection site reactions, and pose significant safety risks5 .
We argue that this alternative framework is a viable solution that provides greater flexibility for managing a limited drug supply and giving healthcare payers financial headroom to support more patients accessing effective weight management treatment18 .
Summary of potential risks in T1D patients using GLP-1 RAs:
- Increased risk of hypoglycemia due to potentiation of insulin effects4 10.
- Risk of diabetic ketoacidosis if insulin doses are reduced improperly4 .
- Common gastrointestinal side effects that may limit tolerability15 11.
- Rare but serious complications such as pancreatitis and gastroparesis15 .
- Safety concerns with compounded and counterfeit GLP-1 products16 5.
| Drug | Weight Loss Effect | Risks in T1D | FDA Approval Status for T1D |
|---|---|---|---|
| Liraglutide | Moderate | Hypoglycemia, ketosis | No |
| Semaglutide | Significant | Hypoglycemia, ketosis | No |
| Tirzepatide | Significant | Limited data, potential similar risks | No |
| Sources: 456 | |||
GLP-1 drugs for diabetes and weight loss have proven to be very effective, but they do have side effects. Among those side effects is "Ozempic face," where skin on the face sags and wrinkles.
GLP-1 Medication Decisions With Type 1 Diabetes
Deciding whether to use GLP-1 receptor agonists in type 1 diabetes requires a careful risk-benefit assessment and close clinical monitoring. Currently, no GLP-1 RA is FDA-approved for T1D, and their use in this population is considered off-label4 113. However, given the rising obesity rates and associated insulin resistance in T1D, some clinicians consider GLP-1 RAs as adjunct therapy to improve weight management and glycemic control3 13.
It’s urgent that researchers investigate the health risks of taking GLP-1s in people with type 1 diabetes, especially because many are already taking them. Longer and larger prospective studies are needed to inform clinical guidance about how this population can safely use GLP-1s2 .
GLP-1 RAs work by mimicking the natural GLP-1 hormone, which triggers insulin release, suppresses glucagon, slows gastric emptying, and promotes satiety10 11. These mechanisms can help reduce insulin requirements and body weight, potentially improving quality of life13 . Clinical trials have shown that liraglutide can reduce HbA1c by a modest amount and promote weight loss of approximately 5% compared to placebo in T1D patients4 13.
When initiating GLP-1 therapy in T1D, insulin doses—especially bolus insulin—should be reduced cautiously to mitigate hypoglycemia risk. Typical dose reductions reported in trials include a 20-33% decrease in bolus insulin and a 10-25% decrease in basal insulin, adjusted based on individual glycemic control and hypoglycemia risk4 13. Close glucose monitoring is essential during dose adjustments.
Long-term safety and cardiovascular benefits of GLP-1 RAs in T1D remain uncertain, as patients with T1D were excluded from large cardiovascular outcome trials12 13. Observational data suggest that obesity in T1D increases the risk of microvascular and macrovascular complications, implying that weight management may confer similar benefits as seen in type 2 diabetes17 13.
The current fervor for GLP-1 receptor agonists in the capital markets as well as in the general public, especially in terms of weight reduction, is probably going to result in overuse. This should raise a red flag18 .
Given the lack of robust evidence, current guidelines recommend cautious use of GLP-1 RAs in T1D, emphasizing patient education about potential risks and benefits4 14. Insurance coverage for GLP-1 RAs prescribed for obesity in T1D is variable and often limited5 .
Considerations for GLP-1 use in T1D:
- GLP-1 RAs are not FDA-approved for T1D but are used off-label for obesity and glycemic control4 1.
- Insulin dose adjustments are critical to avoid hypoglycemia and ketosis4 13.
- Weight loss of ~5% body weight has been observed in clinical trials4 13.
- Long-term cardiovascular and renal benefits in T1D are unknown12 13.
- Close monitoring and patient counseling are essential4 14.
