From the Guidelines
Ozempic (semaglutide) can be used together with insulin for patients with type 2 diabetes who need additional blood sugar control, as evidenced by the most recent guidelines from 2025 1. This combination therapy is generally safe and effective when properly managed by a healthcare provider. The medications have complementary mechanisms - insulin directly lowers blood glucose, while Ozempic improves insulin sensitivity, reduces glucagon secretion, slows gastric emptying, and promotes satiety. Some key points to consider when using Ozempic with insulin include:
- The insulin dose may need to be reduced by 20% initially to prevent hypoglycemia (low blood sugar), especially if the patient's A1C is already below 8% 1.
- Patients should monitor their blood glucose levels more frequently when starting this combination.
- Ozempic is usually administered once weekly via subcutaneous injection, starting at 0.25 mg for four weeks, then increasing to 0.5 mg, with a maximum dose of 2 mg weekly for diabetes management.
- The insulin regimen would continue as prescribed but may require adjustment.
- Patients should be aware of potential overlapping side effects including nausea, vomiting, and increased risk of hypoglycemia, which requires careful monitoring and dose adjustments.
- GLP-1 receptor agonists, such as semaglutide, have been shown to reduce albuminuria and slow eGFR decline, and are preferred agents for patients with chronic kidney disease (CKD) 1.
- When using GLP-1 receptor agonists with insulin or insulin secretagogues, doses of these drugs may be reduced to avoid hypoglycemia, especially in patients with moderate-to-severe CKD 1.
From the FDA Drug Label
The risk of hypoglycemia is increased when OZEMPIC is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin [see Warnings and Precautions (5.5)].
The use of Ozempic with insulin increases the risk of hypoglycemia. To reduce this risk, consider lowering the dose of insulin.
- Key points:
- Increased risk of hypoglycemia when used with insulin
- Reduce insulin dose to lower hypoglycemia risk 2
From the Research
Ozempic with Insulin
- Ozempic, also known as semaglutide, is a glucagon-like peptide-1 (GLP-1) receptor agonist used in the treatment of type 2 diabetes mellitus (T2DM) 3.
- When used in combination with insulin, Ozempic has been shown to have a lower risk of hypoglycemia compared to insulin glargine 3.
- A study comparing the efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with T2DM found that semaglutide resulted in greater reductions in HbA1c and weight, with fewer hypoglycemic episodes 3.
- Another study found that once-weekly GLP-1 RAs, including semaglutide, have a low risk of hypoglycemia, but rates of hypoglycemia are higher when used in combination with sulfonylureas or insulin 4.
Efficacy and Safety
- Semaglutide has been shown to be effective in reducing HbA1c levels and body weight in patients with T2DM 5, 3.
- The safety profile of semaglutide is similar to that of other GLP-1 receptor agonists, with gastrointestinal adverse events being the most common side effects 3, 4.
- A real-world retrospective study found that oral semaglutide is an effective and safe alternative to sulfonylureas for T2DM patients, with no reported hypoglycemic episodes 5.
Combination Therapy
- Adding a sulfonylurea to insulin was associated with more hypoglycemic events compared with insulin alone, but this association was not observed for metformin 6.
- A systematic review and meta-analysis found that insulins, DPP-4 inhibitors, GLP-1 analogues, and thiazolidinediones all produced statistically significant reductions in HbA1c in combination with metformin and a sulphonylurea 7.
- Once-weekly GLP-1 RAs have been evaluated as add-on therapy in combination with a variety of background medications, including metformin, sulfonylureas, and insulin 4.