From the Guidelines
Injectable GLP-1 agonists can improve a patient's A1c by 0.8% to 1.5% from baseline, with some patients experiencing improvements of up to 2%. The most recent and highest quality study, a systematic review and network meta-analysis published in 2024 in the Annals of Internal Medicine 1, supports the use of GLP-1 agonists as a effective treatment for type 2 diabetes. Medications like semaglutide, dulaglutide, liraglutide, and exenatide vary in potency, with once-weekly semaglutide generally showing the greatest A1c reductions.
Key Factors Influencing A1c Reduction
- Baseline A1c: patients with higher starting A1c often see larger reductions
- Medication adherence: consistent use of the medication is crucial for optimal results
- Dosage: higher doses typically yield greater reductions
- Individual response: patients may respond differently to the same medication
Mechanism of Action
GLP-1 agonists work by:
- Stimulating insulin secretion in response to high blood glucose
- Suppressing glucagon release
- Slowing gastric emptying
- Reducing appetite
Optimal Use
For optimal results, GLP-1 agonists should be used alongside lifestyle modifications including diet and exercise. Side effects may include nausea, vomiting, and diarrhea, which typically improve over time. The full effect on A1c is usually seen within 3-6 months of starting therapy at an optimal dose. A consensus report by the American Diabetes Association and the European Association for the Study of Diabetes published in 2018 in Diabetes Care 1 also recommends GLP-1 receptor agonists as a preferred choice to insulin for patients who need the greater glucose-lowering effect of an injectable medication.
From the FDA Drug Label
The mean reduction in HbA1c was -1.3% in the VICTOZA 1.8 mg + metformin + glimepiride treatment group, -1.1% in the VICTOZA 1.8 mg + metformin + glimepiride treatment group compared to placebo, and -1.1% in the VICTOZA 1.8 mg once daily + metformin and/or sulfonylurea treatment group compared to exenatide. In another trial, the estimated treatment difference in HbA1c reduction from baseline between VICTOZA and placebo was -1.06% with a 95% confidence interval of [-1.65%; -0.46%]. The adjusted mean change from baseline in HbA1c after 26 weeks was -0.64% for the VICTOZA+metformin±basal insulin group and 0.42% for the Placebo+metformin±basal insulin group.
The injectable GLP-1 agonist liraglutide can improve a patient’s A1c by -1.1% to -1.3%.
- The reduction in HbA1c was statistically significant in all trials.
- The exact reduction in HbA1c may vary depending on the specific trial and patient population.
- The reduction in HbA1c was compared to placebo or other treatments, such as exenatide. 2 2
From the Research
Injectable GLP-1 Agonists and A1c Improvement
- The exact number of points that an injectable GLP-1 agonist can improve a patient's A1c is not explicitly stated in the provided studies 3, 4, 5, 6, 7.
- However, the studies suggest that GLP-1 receptor agonists are effective in reducing A1c levels in patients with type 2 diabetes 3, 4, 7.
- A study found that liraglutide, a GLP-1 analogue, had a significant effect on A1c levels, with an effect size of -0.09%/mg 6.
- Another study noted that GLP-1 receptor agonists can effectively lower A1c and weight while having a low risk of hypoglycemia 4.
- The American Diabetes Association recommends a target A1c of <7% for most people with type 2 diabetes, and GLP-1 receptor agonists may aid primary care providers in helping patients achieve this target 5.
Factors Influencing A1c Improvement
- The magnitude of effect on A1c and weight, as well as the frequency of adverse effects, may vary between different GLP-1 receptor agonists 4.
- The dose of the GLP-1 analogue may also influence the effect on A1c, weight, and total daily insulin 6.
- Patient preferences, potential adverse effects, and cost may also impact the choice of a specific GLP-1 receptor agonist 7.