Did the addition of semaglutide to 1000 mg of metformin (Metformin) improve hyperglycemia in a 75-year-old male with a fasting blood glucose level of hyperglycemia?

From the Guidelines

The patient's current fasting blood glucose of 174 mg/dL indicates inadequate glycemic control, and adding semaglutide to his metformin regimen is a reasonable next step, with a target HbA1c level between 7% and 8% as recommended by the American College of Physicians 1. The patient should start with semaglutide 0.25 mg subcutaneously once weekly for 4 weeks as an initial dose, then increase to 0.5 mg weekly for at least 4 weeks. If additional glycemic control is needed, the dose can be increased to 1 mg weekly, and potentially to 2 mg weekly if using Wegovy or Ozempic. The patient should continue taking metformin 1000 mg daily as prescribed. Some key points to consider when managing this patient's diabetes include:

• The American College of Physicians recommends aiming for an HbA1c level between 7% and 8% in most patients with type 2 diabetes 1.
• The patient's fasting blood glucose of 174 mg/dL indicates inadequate glycemic control, suggesting that the current metformin monotherapy is insufficient.
• Semaglutide, a GLP-1 receptor agonist, works by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and reducing appetite, complementing metformin's action of decreasing hepatic glucose production and improving insulin sensitivity.
• The patient should be monitored for side effects such as nausea, vomiting, and diarrhea, which can be minimized by gradual dose titration.
• Regular blood glucose monitoring and HbA1c testing every 3 months are recommended to assess treatment efficacy.
• Clinicians should consider deintensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%, as the benefits of more intensive glycemic control may not outweigh the harms in these patients 1. Some benefits of using semaglutide in this patient include:
• Improved glycemic control
• Weight loss
• Reduced risk of major adverse cardiovascular events
• Improved renal outcomes However, potential harms and side effects of semaglutide include:
• Nausea and vomiting
• Diarrhea
• Increased risk of pancreatitis
• Increased risk of thyroid C-cell tumors It is essential to weigh these benefits and harms and consider the patient's individual characteristics, preferences, and comorbidities when making treatment decisions. The American College of Physicians guidance statement on HbA1c targets for glycemic control with pharmacologic therapy in nonpregnant adults with type 2 diabetes mellitus provides a framework for clinicians to make informed decisions about glycemic control in their patients 1. By following this guidance and considering the patient's individual needs and circumstances, clinicians can provide high-quality care and improve outcomes for patients with type 2 diabetes.

From the FDA Drug Label

Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. In patients with type 2 diabetes, treatment with semaglutide 1 mg resulted in reductions in glucose in terms of absolute change from baseline and relative reduction compared to placebo of 29 mg/dL (22%) for fasting glucose.

The addition of semaglutide to 1000 mg of metformin may help assist the patient into a good blood glucose level.

• Fasting blood glucose reduction: The patient's fasting blood glucose was 174, and semaglutide has been shown to reduce fasting glucose by 29 mg/dL (22%) in patients with type 2 diabetes.
• Glucose-dependent mechanism: Semaglutide stimulates insulin secretion and lowers glucagon secretion in a glucose-dependent manner, which may help improve the patient's blood glucose control. 2

From the Research

Efficacy of Semaglutide in Type 2 Diabetes

• The addition of semaglutide to metformin has been shown to improve glycemic control in patients with type 2 diabetes 3, 4.
• A study published in Diabetologia found that semaglutide significantly improved beta cell function and glycemic control in patients with type 2 diabetes, with a significant increase in first- and second-phase insulin secretion 3.
• Another study published in Current Medical Research and Opinion found that once-weekly semaglutide was significantly better than SGLT-2 inhibitors in achieving adequate glycemic control in patients with type 2 diabetes inadequately controlled with metformin monotherapy 4.

Effects on Fasting Blood Glucose

• The study published in Diabetologia found that semaglutide reduced fasting glucose levels, with a significant decrease in fasting glucose AUC0-24h 3.
• The study published in Current Medical Research and Opinion found that once-weekly semaglutide significantly reduced fasting blood glucose levels compared to SGLT-2 inhibitors 4.
• However, the patient's fasting blood glucose level of 174 mg/dL is still above the normal range, and further monitoring and adjustment of treatment may be necessary.

Dose-Dependent Effects of Semaglutide

• A study published in Diabetes Care found that higher doses of semaglutide (up to 16 mg) provided modest additional glucose-lowering effects, with additional weight loss, but also increased the risk of adverse events such as gastrointestinal symptoms 5.
• The optimal dose of semaglutide for this patient would depend on various factors, including their individual response to treatment, medical history, and concomitant medications.

Comparison with Other Antidiabetic Agents

• Semaglutide has been compared to other antidiabetic agents, including SGLT-2 inhibitors, liraglutide, and insulin glargine, and has been found to have superior glycemic efficacy in some studies 4, 6.
• However, the choice of antidiabetic agent depends on various factors, including the patient's individual needs, medical history, and concomitant medications.