Did the addition of semaglutide (GLP-1 receptor agonist) to 1000 mg of metformin (biguanide) improve hyperglycemia in a 75-year-old male with a fasting blood glucose level of hyperglycemia?

From the Guidelines

The patient's current regimen of metformin 1000 mg and semaglutide should be optimized to achieve better glycemic control, with a target fasting glucose of less than 130 mg/dL and HbA1c less than 7% for most adults with diabetes, as recommended by the most recent guidelines 1. The patient's fasting blood glucose of 174 mg/dL indicates that his diabetes is not adequately controlled with the current regimen.

• Increasing the semaglutide dose gradually according to the standard titration schedule, typically starting at 0.25 mg weekly for 4 weeks, then 0.5 mg weekly for 4 weeks, and potentially up to 1 mg weekly if tolerated and needed for glycemic control, is a reasonable approach.
• Additionally, the metformin dose could be optimized to 2000 mg daily (1000 mg twice daily) if the patient is not experiencing gastrointestinal side effects.
• The patient should also be advised on lifestyle modifications including dietary changes (reducing carbohydrate intake, especially refined carbohydrates) and increasing physical activity, which work synergistically with medications to improve insulin sensitivity.
• Semaglutide works by enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, and slowing gastric emptying, while metformin primarily reduces hepatic glucose production and improves peripheral insulin sensitivity. Regular blood glucose monitoring is essential to track progress, and the choice of medication added to metformin should be based on the clinical characteristics of the patient and their preferences, as well as the presence of established ASCVD or indicators of high ASCVD risk, other comorbidities, and risk for specific adverse drug effects, as recommended by the American Diabetes Association/European Association for the Study of Diabetes consensus report 2.
• The most recent guidelines suggest that each new class of noninsulin agents added to initial therapy with metformin generally lowers A1C approximately 0.7–1.0% 1.
• GLP-1 receptor agonists, such as semaglutide, have high glucose-lowering efficacy and minimal risk for hypoglycemia, but may increase the hypoglycemic potential of insulin and sulfonylureas when combined with those medications 3.

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 have helped assist the patient into a better blood glucose control, as semaglutide has been shown to reduce fasting glucose by 29 mg/dL (22%) in patients with type 2 diabetes. However, with a fasting blood glucose of 174, further evaluation and adjustment of the treatment plan may be necessary to achieve optimal glucose control 4.

• The patient's current fasting blood glucose level is above the desired range, indicating that additional interventions may be needed to improve glycemic control.
• Close monitoring of the patient's blood glucose levels and adjustment of the treatment plan as needed is recommended.

From the Research

Patient's Condition

The patient, a 75-year-old male, has a fasting blood glucose level of 174 and is taking 1000 mg of metformin. He is inquiring about the addition of semi glue tide (likely referring to an SGLT2 inhibitor) to his treatment regimen.

Relevant Studies

• The study 5 discusses the combination of SGLT2 inhibitors and GLP-1 receptor agonists as a complementary approach to treating type 2 diabetes, highlighting their beneficial effects on glycemic control, body weight, and cardiovascular risk factors.
• The study 6 compares the efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients, finding that long-acting GLP-1 receptor agonists provide better hypoglycemic effects.
• The study 7 meta-analyzes the effects of GLP-1 agonists compared to DPP-4 inhibitors for managing type 2 diabetes, concluding that GLP-1 agonists yield greater reductions in HbA1c and weight.
• The study 8 reviews the effects of SGLT2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on microvascular complications in diabetes, suggesting that SGLT2 inhibitors and GLP-1 agonists may have promising nephroprotective outcomes.
• The study 9 performs a network meta-analysis to compare the effects of glucose-lowering drugs on mortality, cardiovascular, and renal outcomes in type 2 diabetes, finding that SGLT2 inhibitors and GLP-1 receptor agonists show beneficial effects on mortality and major cardiovascular adverse events.

Key Findings

• SGLT2 inhibitors and GLP-1 receptor agonists may be effective add-ons to metformin therapy for improving glycemic control and reducing cardiovascular risk factors 5, 6, 9.
• GLP-1 agonists may provide greater reductions in HbA1c and weight compared to DPP-4 inhibitors 7.
• SGLT2 inhibitors may have promising nephroprotective outcomes, although more research is needed to fully understand their effects on microvascular complications 8.

Potential Benefits of SGLT2 Inhibitors

• Improved glycemic control
• Reduced body weight
• Decreased cardiovascular risk factors
• Potential nephroprotective effects

Considerations for the Patient

• The patient's fasting blood glucose level of 174 suggests that their current treatment regimen may not be adequately controlling their blood glucose levels.
• The addition of an SGLT2 inhibitor to the patient's metformin therapy may help improve their glycemic control and reduce their cardiovascular risk factors.
• However, the patient's individual response to the medication and potential side effects should be carefully monitored and considered.