​For Independence Blue Cross (IBX) patients with type 2 diabetes (T2DM) and coexisting cardiovascular disease (CVD), or heart failure (HF), providers should consider adding Metformin to regimens with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or sodium–glucose cotransporter-2 (SGLT-2) inhibitors.1 Studies show this combination can further reduce HbA1c levels and improve health outcomes.3,4

Why add Metformin?
Studies show that adding Metformin to existing therapies can provide significant benefits for patients with T2DM.

• Glycemic control: Metformin alone reduces HbA1c by 0.5%–1.5%, and when combined with GLP-1 RAs or SGLT-2 inhibitors, it enhances glycemic control.2

• Mechanism of action: Metformin complements the effects of GLP-1 RAs and SGLT-2 inhibitors by reducing hepatic glucose production, improving insulin sensitivity, and decreasing intestinal glucose absorption.2 Metformin can also provide improved cardiovascular and renal outcomes.3,4,5

• Safety and accessibility: Metformin is cost-effective, safe, widely available across pharmacies, and has a low risk of hypoglycemia, improving adherence and long-term outcomes.2

Clinical considerations for Metformin initiation
Providers can take these steps to optimize Metformin use.

• Dosing: Start with prescribing 500 mg once daily with dinner and gradually increase to 500 mg twice daily as tolerated, up to 2000 mg daily.6
• Managing side effects: Switch to extended release (ER) formulations for persistent gastrointestinal symptoms, encourage hydration, and consider a vitamin B12 supplement for patients on long-term or a higher dose of Metformin, as vitamin B12 depletion typically occurs gradually over extended use.6
• Monitoring: Regularly monitor blood glucose and avoid Metformin 24 hours before and 48 hours after IV contrast imaging to prevent kidney damage.
  

Action steps for providers
Use a patient-centered approach to assess whether Metformin is appropriate for individuals already on GLP-1 RAs or SGLT-2 inhibitors. By incorporating Metformin into the treatment regimen, providers can help optimize care and improve outcomes for patients with T2DM. 3,4

We recognize that you are best qualified to choose the most appropriate medication regime for your patients (our members). For the latest pharmacy news for providers, visit the Pharmacy Resource Page. ​

1. Anderson, J. E. (2020). Combining Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors to Target Multiple Organ Defects in Type 2 Diabetes. Diabetes Spectrum, ds190031. https://doi.org/10.2337/ds19-0031
2. ‌Rhee SY, Kim HJ, Ko SH, Hur KY, Kim NH, Moon MK, Park SO, Lee BW, Choi KM, Kim JH. Monotherapy in Patients with Type 2 Diabetes Mellitus. Diabetes Metab J. 2017;41(5):349-356.
3. Amir Qaseem, Adam J. Obley, Tatyana Shamliyan, et al. Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. Ann Intern Med.2024;177:658-666. [Epub 19 April 2024]. doi:10.7326/M23-2788
4. Gu, J., Meng, X., Guo, Y. et al. The efficacy and safety of liraglutide added to metformin in patients with diabetes: a meta-analysis of randomized controlled trials. Sci Rep 6, 32714 (2016). https://doi.org/10.1038/srep32714
5. Agur, T., Steinmetz, T., Goldman, S. et al. The impact of metformin on kidney disease progression and mortality in diabetic patients using SGLT2 inhibitors: a real-world cohort study. Cardiovasc Diabetol 24, 97 (2025). https://doi.org/10.1186/s12933-025-02643-6
6. Jfairma. (2024, March 22). Metformin - the Johns Hopkins Patient Guide to Diabetes. The Johns Hopkins Patient Guide to Diabetes. https://hopkinsdiabetesinfo.org/medications-for-type-2-diabetes-metformin/

25-0123
​​