What are the purposes, potential effects, and dosing regimens of semaglutide (glucagon-like peptide-1 (GLP-1) receptor agonist) and tirzapatide (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist) for patients with type 2 diabetes?

Patient Education: Semaglutide and Tirzepatide for Type 2 Diabetes

What These Medications Are

Semaglutide and tirzepatide are injectable medications that help control blood sugar and promote weight loss in people with type 2 diabetes. 1 Semaglutide works by activating GLP-1 receptors in your body, while tirzepatide activates both GLP-1 and GIP receptors, making it a dual-action medication. 2, 3

How They Work in Your Body

• Semaglutide stimulates insulin release and reduces glucagon secretion only when your blood sugar is high, which means it won't cause dangerous low blood sugar when used alone. 2
• Tirzepatide works through the same mechanisms but with dual receptor activation, providing enhanced effects on appetite suppression, delayed stomach emptying, and improved insulin secretion. 3
• Both medications slow down how quickly food leaves your stomach, helping you feel full longer and reducing appetite. 1, 2
• These medications are injected under the skin once weekly. 4

Expected Benefits

Blood Sugar Control

• Tirzepatide is the most powerful option available, reducing A1C by 1.24% to 2.58%, with 23% to 62% of patients achieving normal blood sugar levels (A1C below 5.7%). 3
• Semaglutide reduces A1C by approximately 1.39% to 1.96%, depending on the dose used. 1
• Both medications work better than traditional insulin for many patients and have minimal risk of causing dangerously low blood sugar when used alone. 1

Weight Loss

• Tirzepatide produces the greatest weight loss of any diabetes medication, with patients losing 20.9% of their body weight (approximately 11.7 kg) at the highest dose. 4, 3
• Semaglutide produces substantial weight loss of 14.9% (approximately 10.76 kg) when used at the 2.4 mg weekly dose. 4
• For direct comparison: tirzepatide 15 mg produces approximately 6% more weight loss than semaglutide 2.4 mg. 4

Heart and Kidney Protection

• Semaglutide reduces your risk of heart attack, stroke, and cardiovascular death by 26% if you have existing heart disease. 4
• Both medications improve blood pressure, cholesterol levels, and reduce inflammation in blood vessels. 4
• GLP-1 medications like semaglutide provide kidney protection benefits. 1

How to Take These Medications

Semaglutide Dosing Schedule

• Week 1-4: Start with 0.25 mg once weekly 4
• Week 5-8: Increase to 0.5 mg once weekly 4
• Week 9-12: Increase to 1.0 mg once weekly 4
• Week 13-16: Increase to 1.7 mg once weekly 4
• Week 17 onward: Reach maintenance dose of 2.4 mg once weekly 4

Tirzepatide Dosing Schedule

• Starting dose: 5 mg once weekly, designed to minimize stomach side effects while providing benefit. 4
• Your doctor may increase your dose to 10 mg or 15 mg weekly based on your response and tolerance. 4

Important Administration Tips

• Inject under the skin in your abdomen, thigh, or upper arm—all locations work equally well. 2
• If you miss 2 doses in a row, contact your doctor for guidance on restarting. 4
• If you miss 3 or more doses, you may need to restart the gradual dose increase schedule. 4
• Do not use these medications with other GLP-1 medications or DPP-4 inhibitors. 4

What Side Effects to Expect

Common Side Effects (Usually Mild to Moderate)

• Nausea, vomiting, diarrhea, and constipation are the most common side effects, affecting 17-22% of patients with tirzepatide and 18% with semaglutide. 5
• These stomach symptoms are usually worst when starting the medication or increasing doses, then improve over time. 4
• The gradual dose increase schedule is specifically designed to minimize these effects. 4

Serious Side Effects (Rare but Important)

• Pancreatitis (inflamed pancreas): Stop the medication immediately and seek medical care if you develop severe abdominal pain that doesn't go away. 4
• Gallbladder disease: Watch for pain in the upper right abdomen, especially after eating fatty foods. 4
• Delayed stomach emptying: This can affect absorption of other medications, particularly those with narrow safety margins. 4

Who Should NOT Use These Medications

• Absolute contraindication: Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2. 1, 4
• Use caution if you have a history of pancreatitis. 4
• Avoid if you have severe gastrointestinal motility disorders or gastroparesis. 4

Lifestyle Requirements

These medications must be combined with diet and exercise changes—they are not a substitute for healthy lifestyle habits. 4

• Follow a reduced-calorie eating plan as recommended by your healthcare team. 4
• Increase physical activity, particularly resistance training to preserve muscle mass during weight loss. 4
• These medications typically need to be used lifelong—stopping them usually results in significant weight regain (approximately 11.6% of lost weight returns within one year). 4

Monitoring During Treatment

Your healthcare provider will monitor:

• Blood pressure: As you lose weight, your blood pressure medications may need adjustment. 4
• Blood sugar levels: Especially if you're taking insulin or sulfonylureas, as doses may need reduction. 4
• Vitamin B12 levels: If you're also taking metformin, periodic testing is recommended. 1
• Signs of pancreatitis or gallbladder disease: Report any severe abdominal pain immediately. 4
• Thyroid function: Particularly if you have existing thyroid conditions. 4

Special Considerations

For Women of Childbearing Age

• If you use oral contraceptives, switch to non-oral methods or add barrier contraception for 4 weeks after starting tirzepatide and after each dose increase. 4

Before Surgery

• Inform your anesthesiologist that you're taking these medications, as they may increase the risk of aspiration during anesthesia even with extended fasting. 4

Cost Considerations

• Average wholesale prices are approximately $1,600 for a 30-day supply of semaglutide and $1,272 for tirzepatide. 4
• Insurance coverage varies significantly and may be challenging, particularly for obesity management without diabetes. 4
• Discuss cost-reducing strategies with your healthcare team, as medication costs can affect adherence. 1

Which Medication Is Right for You?

Tirzepatide is generally the first choice if you need maximum weight loss and blood sugar control, as it produces superior results compared to semaglutide. 4 However, semaglutide is the preferred option if you have established heart disease, as it has proven cardiovascular benefits in clinical trials. 4

Your doctor will consider:

• Your A1C level and weight loss goals 1
• Whether you have heart disease or kidney disease 1
• Your tolerance of side effects 4
• Insurance coverage and cost 1, 4
• Your preference regarding injection frequency and dosing schedule 4