From the Guidelines
Sitagliptin and Ozempic (semaglutide) should be considered as part of a comprehensive diabetes treatment plan, with Ozempic preferred for patients with established heart or kidney disease due to its additional cardiovascular and renal protective benefits, as supported by the most recent evidence from 2025 1. When treating type 2 diabetes, the choice between sitagliptin and Ozempic depends on various factors, including the patient's medical history, current health status, and treatment goals.
- Sitagliptin is a DPP-4 inhibitor typically taken as a 100mg oral tablet once daily, offering modest glucose control with weight neutrality.
- Ozempic is a GLP-1 receptor agonist administered as a weekly subcutaneous injection, providing stronger blood glucose reduction and significant weight loss benefits (5-15% of body weight). Some patients may take both medications together, as they have complementary mechanisms.
- Ozempic has additional benefits, including cardiovascular and renal protective effects, making it a preferred choice for patients with established heart or kidney disease, as noted in the 2022 guidelines 1. However, side effects differ significantly between the two medications:
- Sitagliptin is generally well-tolerated with minimal gastrointestinal issues.
- Ozempic commonly causes nausea, vomiting, and diarrhea, especially when starting treatment. The most recent evidence from 2025 1 supports the use of semaglutide as a first-line agent for people with chronic kidney disease (CKD), and dedicated kidney outcomes trials have shown that SGLT2 inhibitors have beneficial effects on slowing CKD progression and cardiovascular outcomes in patients with type 2 diabetes.
- Metformin is also a preferred agent for those with CKD due to its well-documented efficacy and safety profile, but its ability to lower glucose levels declines when the eGFR falls below 45 mL/min/1.73 m2, as noted in the 2024 cost-effectiveness review 1. Overall, the choice between sitagliptin and Ozempic should be based on individual patient needs and medical history, with consideration of the latest evidence and guidelines.
From the FDA Drug Label
7 DRUG INTERACTIONS
7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin The risk of hypoglycemia is increased when OZEMPIC is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. 7. 2 Oral Medications OZEMPIC causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications.
The FDA drug label does not answer the question about the interaction between Sitagliptin and Ozempic.
From the Research
Sitagliptin and Ozempic (Semaglutide) Comparison
- Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes, as discussed in studies 2, 3, 4, 5.
- Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist, also used in the treatment of type 2 diabetes, as mentioned in studies 2, 6.
Mechanism of Action
- Sitagliptin works by inhibiting the DPP-4 enzyme, which increases the levels of incretin hormones, leading to increased insulin secretion and decreased glucagon secretion 3, 5.
- Semaglutide, on the other hand, is a GLP-1 receptor agonist that mimics the action of the incretin hormone GLP-1, leading to increased insulin secretion, decreased glucagon secretion, and delayed gastric emptying 2, 6.
Efficacy and Safety
- Both sitagliptin and semaglutide have been shown to be effective in improving glycemic control in patients with type 2 diabetes, with semaglutide demonstrating greater efficacy in reducing HbA1c and body weight 2, 6.
- Sitagliptin has been associated with a low risk of hypoglycemia and a neutral effect on body weight 3, 4, 5.
- Semaglutide has been associated with a higher risk of gastrointestinal adverse events, but has been shown to have a similar safety profile to sitagliptin in terms of serious adverse events 6.