From the Guidelines
Zepbound (tirzepatide) is the most appropriate treatment option for someone with a BMI of 28, high cholesterol, and prediabetes, as it has been shown to have a beneficial effect on weight and glycemic control. According to the 2025 standards of care in diabetes, health care professionals should prioritize the use of glucose-lowering medications with a beneficial effect on weight, such as GLP-1 receptor agonists and dual GIP and GLP-1 receptor agonists like tirzepatide 1.
The typical starting dose of Zepbound is 2.5 mg injected subcutaneously once weekly for the first month, then gradually increased to 5 mg, 7.5 mg, 10 mg, and potentially up to 15 mg weekly, depending on response and tolerability. Common side effects include nausea, diarrhea, vomiting, constipation, and abdominal pain, which often improve over time. Zepbound works by mimicking GLP-1 and GIP hormones, which help regulate blood sugar, increase insulin sensitivity, slow stomach emptying, and reduce appetite. This mechanism not only aids weight loss but can also improve cholesterol levels and help prevent progression from prediabetes to type 2 diabetes.
Some key points to consider when using Zepbound include:
- Weight management pharmacotherapy should be considered along with lifestyle changes, and the potential benefits and risks must be considered 1.
- The preferred pharmacotherapy for people with diabetes and overweight or obesity is a glucagon-like peptide 1 receptor agonist or dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist with greater weight loss efficacy, such as semaglutide or tirzepatide 1.
- Weight management pharmacotherapy indicated for chronic therapy should be continued beyond reaching weight loss goals to maintain the health benefits, as sudden discontinuation often results in weight gain and worsening of cardiometabolic risk factors 1. Lifestyle modifications, including a healthy diet and regular physical activity, should accompany medication use for optimal results, and regular monitoring of blood sugar and cholesterol levels is important to track progress.
From the Research
Zepbound (Tirzepatide) for BMI of 28, High Cholesterol, and Pre-Diabetes
- Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP)-glucagon-like peptide 1 (GLP-1) receptor agonist that has been shown to improve blood pressure and reduce Low-Density Lipoprotein (LDL) cholesterol and triglycerides 2.
- Studies have demonstrated that tirzepatide is efficacious in improving all lipid markers, including cholesterol and triglycerides, with a clear dose-response trend visible across results from groups taking 5,10, and 15 mg of tirzepatide 3.
- Tirzepatide has been shown to significantly decrease body weight, triglycerides, very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels, while increasing high-density lipoprotein cholesterol (HDL-C) levels 4.
Effects on Blood Pressure and Lipids
- Tirzepatide has been shown to result in significant decreases in systolic blood pressure and total cholesterol levels, as well as increases in HDL cholesterol levels and decreases in LDL cholesterol and triglyceride levels 5.
- The predicted 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was reduced in participants treated with tirzepatide, with a greater relative change in risk from baseline to week 72 compared to placebo 6.
Dose-Response Relationship
- Studies have demonstrated a clear dose-response trend across results from groups taking 5,10, and 15 mg of tirzepatide, with the 10 mg and 15 mg doses having a stronger effect on lipid markers and blood pressure 3, 4, 5.
- The 15 mg dose of tirzepatide has been shown to have a more pronounced effect on reducing SBP levels and improving lipid profiles compared to the 5 mg and 10 mg doses 4, 5.