What can cause a decrease in HbA1c (Hemoglobin A1c) levels?

From the Guidelines

A decrease in HbA1c levels can be achieved through lifestyle modifications and medication interventions, with the most recent and highest quality study suggesting that medications such as SGLT-2 inhibitors and GLP-1 receptor agonists can be effective in reducing HbA1c levels without increasing the risk of hypoglycemia 1.

Lifestyle Modifications

Lifestyle modifications are fundamental in achieving a decrease in HbA1c levels, including:

• Regular physical activity, aiming for at least 150 minutes of moderate exercise weekly
• Dietary changes, such as reducing carbohydrate intake, especially refined sugars, and increasing fiber consumption
• Weight loss, if overweight, with even a 5-10% reduction significantly improving glycemic control

Medication Interventions

Medication interventions are often necessary, with:

• Metformin typically used as first-line therapy, starting at 500mg daily and gradually increasing to 1000-2000mg daily in divided doses
• Other medications, such as sulfonylureas, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 receptor agonists, and insulin therapy, may be used when needed
• Consistent medication adherence is crucial for effectiveness, and regular blood glucose monitoring helps track progress between HbA1c tests, which are typically performed every 3-6 months

Recent Study Findings

A recent study published in 2024 found that modification, glycaemic control, blood pressure control, and further cardiovascular risk management can dramatically reduce cardiovascular complications 1. Additionally, the study suggested that SGLT-2 inhibitors should be considered in patients with advanced complications once the ulcer has healed, given their cardiovascular and renal benefits.

Important Considerations

It is essential to note that too rapid reduction in HbA1c in someone who has had very high glycaemia for a long time can cause a paradoxical flare-up of microvascular complications, such as retinopathy, nephropathy, or neuropathy 1. Therefore, blood glucose levels should be gradually lowered over several weeks to avoid detrimental effects.

From the FDA Drug Label

In a randomized, non-blinded, clinical study (Study B, n=320) in which patients with type 1 diabetes were treated for 26 weeks with either twice-daily (morning and bedtime) LEVEMIR or once-daily (bedtime) insulin glargine. Insulin aspart was administered before each meal LEVEMIR-treated patients had a decrease in HbA1c similar to that of insulin glargine-treated patients. In a 24-week, non-blinded, randomized, clinical study (Study E, n=476), LEVEMIR administered twice-daily (before breakfast and evening) was compared to a similar regimen of NPH human insulin as part of a regimen of combination therapy with one or two of the following oral antidiabetes agents (metformin, insulin secretagogue, or α–glucosidase inhibitor) LEVEMIR and NPH similarly lowered HbA1c from baseline DOSAGE AND ADMINISTRATION There is no fixed dosage regimen for the management of diabetes mellitus with glipizide or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient's blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood-glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient's response to therapy.

Decreased HbA1c levels can be caused by:

• Insulin therapy: LEVEMIR and NPH human insulin have been shown to decrease HbA1c levels in patients with type 1 and type 2 diabetes 2
• Oral antidiabetes agents: Metformin, insulin secretagogues, and α–glucosidase inhibitors may also contribute to decreased HbA1c levels when used in combination with insulin therapy 2
• Glipizide: A sulfonylurea-class hypoglycemic that can lower blood glucose levels and decrease HbA1c levels in patients with type 2 diabetes 3
• Combination therapy: Using a combination of insulin and oral antidiabetes agents, such as metformin, can also lead to decreased HbA1c levels 2

From the Research

Factors Contributing to Decreased HbA1c Levels

Several factors can contribute to a decrease in HbA1c levels, including:

• Medications such as metformin, sulfonylureas, pioglitazone, and sitagliptin 4
• Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide and liraglutide 4, 5, 6
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin 4
• Combination therapy, including metformin plus a GLP-1 receptor agonist or a thiazolidinedione 4
• Lifestyle modifications, such as personalized nutrition, progressive fitness, and lifestyle modification 7
• Weight loss, which can be achieved through lifestyle modifications or medications such as GLP-1 receptor agonists 4, 7, 5

Studies Demonstrating Decreased HbA1c Levels

Several studies have demonstrated significant reductions in HbA1c levels with various interventions, including:

• A study comparing metformin-based dual-agent oral treatment approaches, which showed a reduction in HbA1c from 11.6% to 6.0% 4
• A 32-week study of the combination of rosiglitazone with metformin, which showed a mean HbA1c reduction of 2.3% 4
• A study evaluating the effectiveness of a comprehensive and multi-interventional diabetes care program, which showed a significant reduction in HbA1c level, fasting blood sugar, and weight 7
• A meta-analysis of randomized controlled trials assessing the efficacy of GLP-1 receptor agonists, which showed a statistically significant reduction in HbA1c compared to placebo 5
• A 52-week, randomized, multicenter trial assessing the long-term efficacy and safety of adding liraglutide to existing sulfonylurea therapy, which showed a reduction in HbA1c from 8.61 to 7.33% 6