What are the mono and dual therapy options for managing elevated Hemoglobin A1c (HbA1c) levels?

From the Guidelines

For managing elevated HbA1c levels, metformin is the preferred first-line monotherapy option, typically started at 500mg once or twice daily and titrated up to 1000mg twice daily as tolerated, as recommended by the most recent guidelines 1. Metformin works by decreasing hepatic glucose production and improving insulin sensitivity, with the added benefits of weight neutrality or modest weight loss and low hypoglycemia risk. If monotherapy is insufficient or contraindicated, dual therapy options include adding a second agent such as:

• a sulfonylurea (like glipizide 5-20mg daily or glimepiride 1-8mg daily)
• a DPP-4 inhibitor (like sitagliptin 100mg daily)
• a GLP-1 receptor agonist (like semaglutide 0.25-1mg weekly)
• an SGLT-2 inhibitor (like empagliflozin 10-25mg daily)
• a thiazolidinedione (like pioglitazone 15-45mg daily) The choice of second agent should be individualized based on patient characteristics, comorbidities, and preferences. For example, SGLT-2 inhibitors or GLP-1 receptor agonists are preferred in patients with established cardiovascular disease or chronic kidney disease, while DPP-4 inhibitors may be better for elderly patients due to their neutral weight effect and low hypoglycemia risk. Treatment should be reassessed every 3-6 months with HbA1c monitoring, with a target typically between 7-8% depending on the patient's age, comorbidities, and hypoglycemia risk, as supported by recent studies 1. Key considerations in selecting a second agent include efficacy, contraindications, drug interactions, comorbidities, and potential adverse effects, emphasizing the importance of a patient-centered approach in managing type 2 diabetes 1.

From the FDA Drug Label

14 CLINICAL STUDIES

In glycemic control trials in adults, VICTOZA has been studied as monotherapy and in combination with one or two oral anti-diabetic medications or basal insulin. Monotherapy In this 52-week trial, 746 adult patients with type 2 diabetes mellitus were randomized to VICTOZA 1.2 mg, VICTOZA 1. 8 mg, or glimepiride 8 mg. Treatment with VICTOZA 1.8 mg and 1. 2 mg resulted in a statistically significant reduction in HbA1c compared to glimepiride

14 CLINICAL STUDIES

JARDIANCE has been studied as monotherapy and in combination with metformin, sulfonylurea, pioglitazone, linagliptin, and insulin. Monotherapy A total of 986 patients with type 2 diabetes participated in a double-blind, placebo-controlled study to evaluate the efficacy and safety of JARDIANCE monotherapy At Week 24, treatment with JARDIANCE 10 mg or 25 mg daily provided statistically significant reductions in HbA1c

The mono therapy options for managing elevated Hemoglobin A1c (HbA1c) levels are:

• VICTOZA (liraglutide) 1.2 mg or 1.8 mg
• JARDIANCE (empagliflozin) 10 mg or 25 mg The dual therapy options are:
• VICTOZA (liraglutide) 1.2 mg or 1.8 mg + metformin
• JARDIANCE (empagliflozin) 10 mg or 25 mg + metformin 2 and 3

From the Research

Mono Therapy Options

• Metformin is a commonly used monotherapy option for managing elevated Hemoglobin A1c (HbA1c) levels, with studies showing it can lower HbA1c levels by 1.1-1.2% 4, 5.
• Metformin works by enhancing insulin sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose output, with minimal risk of hypoglycaemia 4.
• Metformin is usually well tolerated, with the most common side effects being gastrointestinal, and it does not increase the risk of lactic acidosis significantly 4.

Dual Therapy Options

• Combination therapy with glyburide and metformin has been shown to be more effective than monotherapy with either drug alone, with a superior mean reduction in HbA1c of -2.27% 6.
• The combination of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) has been proposed as a dual therapy option, addressing complementary pathophysiological mechanisms and enhancing efficacy in achieving target HbA1c levels 7.
• Dual therapy with SGLT2i and metformin has also been shown to be effective in reducing HbA1c and body weight, with studies suggesting it is more effective than monotherapy with metformin alone 8.
• The combination of SGLT2i and GLP-1 RA or dual gastric inhibitory polypeptide (GIP)/GLP-1 RA may be considered for most patients with type 2 diabetes who do not have contraindications, due to their favourable safety profiles and potential to prevent complications of type 2 diabetes 7.