Is Zepbound (tirzepatide) approved for the treatment of prediabetes?

Zepbound (Tirzepatide) is NOT Approved for Prediabetes Treatment

Zepbound (tirzepatide) is not FDA-approved for the treatment of prediabetes, despite showing promising results in delaying progression from prediabetes to type 2 diabetes.

Current Approved Indications for Tirzepatide

Tirzepatide is currently approved for:

• Zepbound: FDA-approved in November 2023 for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity 1
• Mounjaro: FDA-approved for type 2 diabetes management

Evidence on Tirzepatide in Prediabetes

While not approved specifically for prediabetes, recent research shows significant potential:

• In the SURMOUNT-1 trial, tirzepatide demonstrated substantial weight reduction and markedly lower risk of progression to type 2 diabetes compared to placebo in people with obesity and prediabetes over a 3-year period 2
• After 176 weeks of treatment, only 1.3% of participants with prediabetes who received tirzepatide developed type 2 diabetes, compared to 13.3% in the placebo group (hazard ratio 0.07) 2
• Weight loss at 176 weeks was significant: -12.3% with 5mg dose, -18.7% with 10mg dose, and -19.7% with 15mg dose, versus -1.3% with placebo 2

Guidelines for Prediabetes Management

Current guidelines for prediabetes management focus on:

1. Lifestyle interventions: The European Society of Cardiology (ESC) recommends lifestyle intervention as the primary approach to delay/prevent conversion from prediabetes to type 2 diabetes 1

2. Medication considerations:

   • RAAS blockers rather than beta-blockers/diuretics are recommended for blood pressure control in prediabetes 1
   • Guidelines do not currently recommend GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists specifically for prediabetes

Clinical Implications

Despite not being FDA-approved for prediabetes, clinicians should note:

• Tirzepatide produces superior weight loss compared to other GLP-1 receptor agonists, with meta-analyses showing tirzepatide 15mg weekly provides 5.1% more weight loss than semaglutide 2.4mg weekly 1
• Tirzepatide is generally well-tolerated, with gastrointestinal side effects (nausea, vomiting, diarrhea) being the most common adverse events, primarily during dose escalation 2
• The European Association for the Study of the Liver (EASL) notes that GLP-1 receptor agonists are safe to use in metabolic dysfunction-associated steatotic liver disease (MASLD) and should be used for their respective indications (type 2 diabetes and obesity) 1

Key Considerations for Off-Label Use

If considering off-label use for prediabetes:

• Safety profile: Monitor for gastrointestinal adverse events, which are more common with higher doses of tirzepatide compared to placebo and insulin 3
• Cost and access: Tirzepatide may not be covered by insurance for prediabetes, creating significant financial barriers
• Patient selection: Most appropriate for patients with both obesity/overweight and prediabetes who have failed lifestyle interventions

Conclusion

While tirzepatide shows promising results in preventing progression from prediabetes to type 2 diabetes, it is currently only approved for chronic weight management in adults with obesity or overweight with weight-related comorbidities, and for type 2 diabetes management. Lifestyle interventions remain the first-line approach for prediabetes management according to current guidelines.