Using Ozempic (Semaglutide) for Weight Loss in Type 1 Diabetes
Ozempic (semaglutide) is not FDA-approved for type 1 diabetes but can be considered off-label for weight loss in patients with type 1 diabetes and obesity, particularly when combined with automated insulin delivery systems, though this requires careful patient selection, intensive monitoring for hypoglycemia and diabetic ketoacidosis, and explicit informed consent about off-label use. 1, 2, 3
Current Regulatory Status and Evidence Base
Semaglutide remains investigational in type 1 diabetes despite FDA approval for type 2 diabetes and obesity treatment in non-diabetic individuals. 1, 2 The American Diabetes Association 2025 guidelines acknowledge that GLP-1 receptor agonists have been studied in type 1 diabetes, with retrospective case series revealing potential benefits on body weight and glycemic metrics when semaglutide is added for individuals with type 1 diabetes and obesity. 1 Prospective studies using semaglutide in this population are ongoing. 1
The most compelling recent evidence comes from the 2025 ADJUST-T1D trial, which demonstrated that in adults with type 1 diabetes and obesity using automated insulin delivery systems, semaglutide 1 mg weekly achieved a composite outcome of >70% time in range, <4% time below range, and ≥5% weight reduction in 36% of patients versus 0% with placebo. 3 This trial showed an 8.8 kg greater weight loss and 8.8 percentage point improvement in time in range compared to placebo over 26 weeks. 3
Clinical Benefits Demonstrated
Glycemic Improvements
- Liraglutide 1.8 mg daily (the most extensively studied GLP-1 RA in type 1 diabetes) showed modest A1C reductions of 0.4%, weight decreases of 5 kg, and reductions in insulin doses. 1
- Real-world data with semaglutide in 50 overweight/obese type 1 diabetes patients showed significant declines in BMI (7.9%), body weight (15.9 lbs), HbA1c, glucose variability (SD and CV), and increased time in range compared to matched controls. 4
- The ADJUST-T1D trial demonstrated a 0.3 percentage point reduction in HbA1c with semaglutide versus placebo. 3
Weight Loss Efficacy
- Semaglutide consistently produces clinically meaningful weight loss in type 1 diabetes patients with obesity, with reductions ranging from 8-16 lbs in real-world studies. 4, 3
Critical Safety Considerations and Risk Mitigation
Hypoglycemia Risk
- Insulin dose adjustment is mandatory: The primary safety concern is hypoglycemia if insulin doses are not appropriately reduced when initiating semaglutide. 2
- The ADJUST-T1D trial reported two severe hypoglycemia events in both semaglutide and placebo groups, suggesting the risk is manageable with proper insulin adjustment. 3
- Patients must have glucagon available for emergency hypoglycemia management. 2
- Real-world data showed no difference in time below range when semaglutide was used with appropriate insulin adjustments. 4
Diabetic Ketoacidosis (DKA) Risk
- While SGLT2 inhibitors carry an eightfold increased DKA risk in type 1 diabetes, this has not been prominently reported with GLP-1 receptor agonists. 1, 2
- No DKA events occurred in the ADJUST-T1D trial. 3
- Patients must be educated on DKA signs and symptoms as a precautionary measure. 2
Gastrointestinal Side Effects
- Nausea, vomiting, and diarrhea are expected side effects that typically diminish over time. 2
Patient Selection Algorithm
Ideal candidates for off-label semaglutide in type 1 diabetes:
BMI criteria: ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities (hypertension, dyslipidemia). 2
Insulin delivery system: Preferably using automated insulin delivery or insulin pump therapy for easier dose titration. 4, 3
Glycemic monitoring: Must have continuous glucose monitoring capability for safety monitoring. 4, 3
Hypoglycemia awareness: Intact hypoglycemia awareness and ability to recognize/treat low blood sugars. 2
Patient engagement: Willing and able to perform frequent glucose monitoring and insulin dose adjustments. 2
No recent DKA: Absence of recurrent ketoacidosis episodes. 1
Practical Implementation Protocol
Initiation and Titration
- Start with semaglutide 0.25 mg weekly, titrating to 0.5 mg after 4 weeks, then to 1 mg after another 4 weeks if additional benefit needed. 3
- Reduce total daily insulin dose by 10-20% at initiation to prevent hypoglycemia. 2
- Monitor CGM data closely during the first 2-4 weeks for hypoglycemia patterns. 4
Ongoing Monitoring
- Weekly CGM review during titration phase. 4, 3
- Assess time in range (target >70%), time below range (target <4%), and glucose variability. 3
- Monitor weight, HbA1c every 3 months. 4
- Adjust insulin doses based on CGM trends, typically requiring 20-30% total insulin reduction over 6 months. 4
Informed Consent Requirements
- Explicitly inform patients this is off-label use not FDA-approved for type 1 diabetes. 2
- Document discussion of potential risks including hypoglycemia and theoretical DKA risk. 2
- Explain the need for intensive monitoring and insulin dose adjustments. 2
Important Caveats
The 2025 ADA guidelines note that liraglutide was assessed for impact on C-peptide in individuals with type 1 diabetes and residual β-cell function, showing no protective effect during treatment and worsening C-peptide loss after discontinuation compared to placebo. 1 This suggests GLP-1 RAs do not preserve β-cell function in type 1 diabetes and should not be used for this purpose.
Weight management pharmacotherapy should be continued long-term to maintain benefits, as sudden discontinuation often results in weight regain and worsening cardiometabolic risk factors. 1 This creates a commitment to ongoing therapy and cost considerations.
The shortage of GLP-1 RAs due to off-label weight loss prescribing has made it difficult for patients with FDA-approved indications (type 2 diabetes) to obtain these medications. 5 This ethical consideration should factor into prescribing decisions for off-label use.