Can semaglutide (glucagon-like peptide-1 receptor agonist) be used in type 1 diabetes mellitus (type 1 DM)?

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Last updated: June 20, 2025View editorial policy

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From the Guidelines

Semaglutide can be used off-label in select patients with type 1 diabetes mellitus as an adjunct to insulin therapy, but its use requires careful consideration of the potential benefits and risks, including increased hypoglycemia and diabetic ketoacidosis, as noted in recent guidelines 1. When considering semaglutide for type 1 DM, it's essential to weigh the potential advantages, such as reduced insulin requirements, improved glycemic control, weight loss, and decreased glycemic variability, against the potential risks. The mechanism of action of semaglutide, a glucagon-like peptide-1 receptor agonist, involves slowing gastric emptying, enhancing glucose-dependent insulin secretion from any remaining beta cells, and suppressing glucagon release. However, as with other GLP-1 receptor agonists, semaglutide can increase the risk of hypoglycemia when combined with insulin, necessitating dosage adjustments of insulin. Furthermore, there's a potential risk of diabetic ketoacidosis, particularly if insulin doses are reduced too aggressively, as highlighted in studies on similar agents like liraglutide 1 and more recent guidelines on pharmacologic approaches to glycemic treatment 1.

Key considerations for the use of semaglutide in type 1 DM include:

  • Close medical supervision with regular monitoring of blood glucose levels and ketones.
  • Careful adjustment of insulin doses to minimize the risk of hypoglycemia and diabetic ketoacidosis.
  • Patient selection, focusing on those who may benefit from improved glycemic control, weight loss, and reduced insulin requirements.
  • Awareness of the potential for increased adverse events, such as hypoglycemia and diabetic ketoacidosis, as reported in clinical trials with similar agents 1.
  • Starting with a low dose, such as 0.25 mg subcutaneously once weekly, with potential titration to higher doses based on individual response and tolerability.

From the FDA Drug Label

• Not indicated for use in type 1 diabetes mellitus or treatment of diabetic ketoacidosis (1) The FDA drug label does not support the use of semaglutide in type 1 DM, it is not indicated for this condition 2.

From the Research

Semaglutide in Type 1 Diabetes Mellitus (Type 1 DM)

  • Semaglutide, a glucagon-like peptide-1 receptor agonist, has been studied for its potential use in type 1 diabetes mellitus (type 1 DM) 3, 4, 5.
  • A retrospective chart review study found that semaglutide was effective in lowering body weight and BMI, and improving glycemic metrics in overweight and obese patients with type 1 DM 3.
  • Another study discussed the use of adjunct therapies, including semaglutide, in the treatment of type 1 diabetes, highlighting the need for innovation in this area 4.
  • The safety of semaglutide has been evaluated, and it has been found to have a favorable risk/benefit profile, with mostly mild-to-moderate and transient gastrointestinal disturbances, and an increased risk of biliary disease 6.
  • A phase 2 double-blinded randomized placebo-controlled trial is currently underway to study the effects of semaglutide on cardiometabolic risk in type 1 diabetes (RESET1) 5.
  • The study will investigate whether semaglutide can improve markers of cardiometabolic health in type 1 DM, and explore underlying mechanisms predicting response, including insulin resistance and incretin hormone status 5.

Key Findings

  • Semaglutide may be effective in improving glycemic control and reducing body weight in overweight and obese patients with type 1 DM 3.
  • Semaglutide has a favorable risk/benefit profile, with a low risk of severe adverse events 6.
  • Further studies are needed to fully evaluate the potential benefits and risks of semaglutide in type 1 DM 4, 5.

Ongoing Research

  • The RESET1 trial is currently underway to study the effects of semaglutide on cardiometabolic risk in type 1 diabetes 5.
  • The trial will provide valuable insights into the potential benefits and risks of semaglutide in type 1 DM, and may inform future treatment options for patients with this condition 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Safety of Semaglutide.

Frontiers in endocrinology, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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