What are the effects of adding Ozempic (semaglutide) to diabetes patients already on insulin and metformin?

From the Guidelines

Adding Ozempic (semaglutide) to a regimen of insulin and metformin for diabetes patients is often beneficial for improving glycemic control and may allow for insulin dose reduction, as supported by the most recent guidelines 1. When considering the addition of Ozempic to insulin and metformin, it's essential to weigh the potential benefits and risks. The American Diabetes Association recommends a patient-centered approach to choosing pharmacologic treatment, considering factors such as efficacy, comorbidities, hypoglycemia risk, effects on body weight, side effects, cost, and patient preferences 1.

Key Considerations

• Start with a low dose of 0.25 mg once weekly by subcutaneous injection for 4 weeks as an initial titration dose, then increase to 0.5 mg weekly 1.
• If additional glycemic control is needed after at least 4 weeks, the dose can be increased to 1 mg weekly, with a maximum dose of 2 mg weekly if necessary.
• When adding Ozempic, consider reducing basal insulin by 10-20% initially to prevent hypoglycemia, especially in patients with well-controlled blood glucose or HbA1c below 8% 1.
• Monitor blood glucose closely during the first 4-8 weeks of combination therapy and adjust insulin as needed.

Mechanism of Action

Ozempic works by enhancing glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting satiety, which complements the actions of metformin (which reduces hepatic glucose production) and insulin 1.

Potential Benefits

• Improved glycemic control
• Potential for insulin dose reduction
• Better 24-hour glucose coverage
• Promotion of weight loss
• Potential reduction in cardiovascular risk

Common Side Effects

• Nausea
• Vomiting
• Diarrhea These side effects typically improve over time, and patients should be advised to stay hydrated and start with smaller meals 1.

From the FDA Drug Label

In a 30-week, double-blind trial (NCT02305381), 397 patients with type 2 diabetes mellitus inadequately controlled with basal insulin, with or without metformin, were randomized to OZEMPIC 0.5 mg once weekly, OZEMPIC 1 mg once weekly, or placebo. Treatment with OZEMPIC resulted in a statistically significant reduction in HbA1c after 30 weeks of treatment compared to placebo (see Table 7).

The effects of adding Ozempic (semaglutide) to diabetes patients already on insulin and metformin include:

• A statistically significant reduction in HbA1c
• A decrease in FPG (mg/dL)
• An increase in the percentage of patients achieving HbA1c <7%
• A reduction in body weight 2

From the Research

Effects of Adding Ozempic (Semaglutide) to Diabetes Patients Already on Insulin and Metformin

The provided studies do not directly address the effects of adding Ozempic (semaglutide) to diabetes patients already on insulin and metformin. However, we can look at the effects of adding other medications to insulin and metformin:

• Adding saxagliptin to patients with type 2 diabetes on insulin alone or combined with metformin improves glycemic control, with significant reductions in HbA1c and postprandial glucose 3.
• Combining insulin with metformin results in superior glycemic control compared to insulin therapy alone, with reduced insulin requirements and weight gain 4.
• In obese type 2 diabetic patients, adding metformin to intensive insulin therapy improves glycemia and reduces exogenous insulin requirements, but does not affect hyperinsulinemia 5.
• GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors improve glycemic control when added to insulin, with a low propensity for hypoglycemia and weight gain 6, 7.

Key Findings

• The combination of insulin and metformin is effective in improving glycemic control and reducing insulin requirements.
• Adding other medications, such as saxagliptin, to insulin and metformin can further improve glycemic control.
• GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors are potential treatment options for insulin combination therapy, with benefits including improved glycemic control and reduced risk of hypoglycemia and weight gain.

Medication Combinations

• Insulin and metformin: improves glycemic control, reduces insulin requirements, and weight gain 4.
• Saxagliptin and insulin (with or without metformin): improves glycemic control, with significant reductions in HbA1c and postprandial glucose 3.
• GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors with insulin: improves glycemic control, with a low propensity for hypoglycemia and weight gain 6, 7.