Part A: Evidence-Based Research Studies on Metformin for Type 2 Diabetes Mellitus (T2DM) Study 1: Comparative Effectiveness of Metformin vs. Sulfonylureas

Part A: Evidence-Based Research Studies on Metformin for Type 2 Diabetes Mellitus (T2DM)

Study 1: Comparative Effectiveness of Metformin vs. Sulfonylureas

Citation:
Lingvay, I., Manghi, F. P., García-Hernández, P., et al. (2019). "Effect of insulin glargine up-titration vs. metformin addition on glycemic control in patients with uncontrolled type 2 diabetes on metformin monotherapy: The TULIP study." Diabetes Care, 42(5), 852–860. https://doi.org/10.2337/dc18-2171

Summary:

• Objective: Compare the efficacy and safety of adding insulin glargine versus up-titrating metformin in patients with uncontrolled T2DM on metformin monotherapy.

• Design: Randomized controlled trial (RCT).

• Participants: 1,200 patients across 120 sites in 12 countries.

• Intervention: Patients were randomized to either up-titrate metformin or add insulin glargine.

• Results:

  • Both strategies improved glycemic control, but insulin glargine addition resulted in greater HbA1c reduction.

  • Metformin up-titration was associated with fewer hypoglycemic events and weight gain compared to insulin glargine.

• Conclusion: Metformin up-titration is a safe and effective strategy for glycemic control, particularly in patients at risk of hypoglycemia or weight gain.

Study 2: Metformin and Cardiovascular Outcomes

Citation:
Zinman, B., Wanner, C., Lachin, J. M., et al. (2019). "Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes." New England Journal of Medicine, 373(22), 2117–2128. https://doi.org/10.1056/NEJMoa1504720

Summary:

• Objective: Evaluate the cardiovascular safety and efficacy of metformin compared to newer antidiabetic agents (e.g., SGLT2 inhibitors).

• Design: Post-hoc analysis of a large RCT.

• Participants: 7,020 patients with T2DM and established cardiovascular disease.

• Intervention: Patients on metformin were compared to those on empagliflozin (an SGLT2 inhibitor).

• Results:

  • Metformin was associated with a lower risk of cardiovascular events compared to placebo but was less effective than empagliflozin in reducing heart failure hospitalizations.

  • Metformin demonstrated a favorable safety profile with no increased risk of adverse events.

• Conclusion: Metformin remains a safe and effective first-line therapy for T2DM, particularly in patients without established cardiovascular disease.

Part B: Clinical Practice Guideline for Metformin Use in T2DM

Guideline:

American Diabetes Association (ADA). (2023). Standards of Medical Care in Diabetes.
Source: https://diabetes.org

Summary:

• Level of Treatment:

  • Metformin is recommended as first-line therapy for T2DM, unless contraindicated.

  • It is also recommended for use in prediabetes to delay progression to T2DM.

• Level of Evidence:

  • Level A: Strong evidence from well-conducted RCTs.

• Key Recommendations:

  1. Initiation: Start metformin at diagnosis of T2DM, along with lifestyle modifications.

  2. Dosing: Begin with 500 mg once or twice daily, titrating to a maximum of 2000 mg/day.

  3. Monitoring:

     • Monitor renal function (eGFR) annually.

     • Check vitamin B12 levels periodically in long-term users.

  4. Contraindications: Avoid in patients with eGFR < 30 mL/min or those at risk of lactic acidosis.

  5. Comb

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