What are the recommendations for a male patient with a body mass index (BMI) of 39, impaired glucose regulation (pre-diabetes) with a hemoglobin A1c (HbA1c) level of 5.1%, currently taking metformin (Metformin) 500 milligrams twice daily, after insurance denial of Semaglutide (Wegovy)?

From the Guidelines

For a prediabetic male with a BMI of 39 who can no longer access Wegovy, I strongly recommend continuing metformin 500mg twice daily while implementing a comprehensive lifestyle approach focused on diet and exercise, as this combination has been shown to be effective in preventing or delaying the onset of type 2 diabetes, especially in individuals with a high BMI 1. The lifestyle approach should include a calorie deficit of 500-750 calories daily through a Mediterranean or DASH diet pattern, emphasizing vegetables, lean proteins, whole grains, and healthy fats while limiting refined carbohydrates and processed foods. Incorporating 150 minutes of moderate-intensity exercise weekly (30 minutes, 5 days per week), combining cardio and resistance training, is also crucial. Consider discussing with your physician alternative GLP-1 medications like Ozempic (semaglutide) or Mounjaro (tirzepatide), or more affordable options like Victoza (liraglutide), as metformin may be less effective than lifestyle modification in some individuals, but it is still a valuable pharmacological therapy for diabetes prevention, especially for those with a BMI ≥35 kg/m² 1. You might also explore patient assistance programs from manufacturers or appeal the insurance denial with your doctor's help. Regular blood glucose monitoring is essential, as is addressing sleep quality and stress management. This approach works by improving insulin sensitivity through exercise, reducing glucose absorption with dietary changes, and maintaining the benefits of metformin which decreases liver glucose production and enhances peripheral glucose uptake. Key points to focus on include:

• Weight management through caloric restriction and increased physical activity
• Dietary changes to reduce saturated fats, cholesterol, and trans-fatty acids
• Increased consumption of fruits, vegetables, whole grains, and lean proteins
• Regular physical activity, including moderate-intensity exercise and resistance training
• Stress management and adequate sleep
• Regular monitoring of blood glucose levels and adjustment of the treatment plan as needed, based on the most recent and highest quality evidence available 1.

From the FDA Drug Label

OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated as: • an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1). • to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease (1) DOSAGE AND ADMINISTRATION • Start at 0.25 mg once weekly. After 4 weeks, increase the dose to 0. 5 mg once weekly. If after at least 4 weeks additional glycemic control is needed, increase to 1 mg once weekly (2.1).

The patient is prediabetic with a BMI of 39 and an A1c of 5.1, and is currently on metformin 500 bid. Since the patient was previously on Wegovy (semaglutide) but insurance has denied this, semaglutide (OZEMPIC) could be considered as an alternative, given its indication for improving glycemic control in adults with type 2 diabetes mellitus. However, the patient is prediabetic, not diabetic, so the use of OZEMPIC would be off-label.

• The patient should be counseled on the potential risks and benefits of using OZEMPIC, including the risk of thyroid C-cell tumors and pancreatitis.
• The dosage of OZEMPIC should be started at 0.25 mg once weekly and increased as needed to 0.5 mg or 1 mg once weekly.
• The patient should be monitored for adverse reactions, such as nausea, vomiting, and diarrhea, and for signs of pancreatitis or thyroid tumors.
• It is also important to continue diet and exercise as part of the treatment plan to improve glycemic control and aid in weight loss 2.

From the Research

Recommendations for Male with Prediabetes and High BMI

Given the patient's current situation, with a BMI of 39, A1c of 5.1, and being on metformin 500 bid, the following recommendations can be considered:

• Lifestyle Modification: Intensive lifestyle modification, including calorie restriction, increased physical activity (≥150 min/wk), self-monitoring, and motivational support, has been shown to decrease the incidence of diabetes by 6.2 cases per 100 person-years during a 3-year period 3.
• Metformin Therapy: Metformin has been found to decrease the risk of diabetes among individuals with prediabetes by 3.2 cases per 100 person-years during 3 years, and is most effective for individuals with a BMI of 35 or greater, fasting plasma glucose level of 110 mg/dL or higher, or HbA1c level of 6.0% or higher 3.
• Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs): GLP-1RAs have been shown to significantly increase the incidence of prediabetes reversion to the normoglycemic state and prevent new-onset diabetes, with significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL 4.
• Combination Therapy: Combination therapy with metformin, premixed insulin, and a GLP-1 receptor agonist has been found to improve glycemic control in patients with uncontrolled type 2 diabetes, with a decreased cumulative daily dose of insulin 5.

Considerations for Weight Loss

For weight loss, the following options can be considered:

• GLP-1RAs: GLP-1RAs have been found to induce significant weight loss, with liraglutide 3.0 mg daily inducing a weight loss of 6-8%, semaglutide 2.4 mg once weekly improving weight loss to about 12-15%, and the dual GIP/GLP-1 receptor agonist tirzepatide once weekly inducing a weight loss of about 20% in obese people without diabetes 6.
• Lifestyle Modification: Lifestyle modification, including a healthy, plant-based diet and regular physical activity, can also aid in weight loss and improve overall health 7.