From the Guidelines
The metformin dose should be increased to 1000 mg twice daily since the patient's fasting blood glucose of 174 mg/dL indicates inadequate glycemic control despite three months of treatment. This recommendation is based on the American Diabetes Association's standards of medical care in diabetes, which suggest that metformin is the preferred initial pharmacologic agent for type 2 diabetes management 1. According to the guidelines, if lifestyle efforts and metformin therapy at the initial dose do not achieve or maintain glycemic goals, the dose should be increased or a second agent should be added 1.
The patient's current dose of 750 mg has not achieved target fasting glucose levels, which should ideally be below 130 mg/dL. Metformin can be safely titrated up to a maximum of 2000-2550 mg daily, divided into two or three doses 2. When increasing the dose, it is recommended to take it with meals to minimize gastrointestinal side effects like nausea, diarrhea, and abdominal discomfort. If the patient experiences significant side effects, consider extended-release formulations which are often better tolerated.
Key considerations for adjusting metformin dosage include:
- Monitoring for gastrointestinal side effects and adjusting the dose or formulation as needed
- Assessing the patient's renal function, as metformin can be used in patients with an estimated glomerular filtration rate as low as 30 mL/min/1.73 m2 2
- Periodic testing of vitamin B12 levels, especially in patients with anemia or peripheral neuropathy, due to the potential for vitamin B12 deficiency with long-term metformin use 2
- Scheduling a follow-up within 1-2 weeks to assess the patient's response to the dose adjustment and tolerability.
From the FDA Drug Label
The results are presented in Table 7 Table 7: Mean Change in Fasting Plasma Glucose and HbA1c at Week 29 Comparing Metformin Hydrochloride Tablets vs Placebo in Patients with Type 2 Diabetes Mellitus Not statistically significant Metformin Hydrochloride Tablets (n=141) Placebo (n=145) p-Value FPG (mg/dL) Baseline 241.5 237.7 NS Change at FINAL VISIT –53.0 6.3 0.001
The patient's fasting blood glucose is 174, which is still elevated. The drug label does not provide a clear answer on when to change the order of metformin. No conclusion can be drawn. 3
From the Research
Patient's Current Condition
- The patient is a 46-year-old female diagnosed with type 2 diabetes about three months ago.
- She was started on metformin 750 mg.
- Her current fasting blood glucose is 174.
Metformin Therapy
- Metformin is commonly used as a first-line treatment for type 2 diabetes 4.
- It enhances the action of insulin in the liver and skeletal muscle, and its efficacy for delaying or preventing the onset of diabetes has been proven in large, well-designed, randomized trials 4.
- However, the current fasting blood glucose level of 174 may indicate that the patient's diabetes is not well-controlled on metformin alone.
Alternative Therapies
- Pioglitazone has been shown to improve glycemic control in patients with type 2 diabetes, and its addition to metformin or sulfonylurea therapy has been found to be effective in reducing HbA1c levels and improving insulin sensitivity 5, 6, 7, 8.
- Compared to metformin, pioglitazone has been found to have a more significant effect on post-load glycemia and composite insulin sensitivity index (CISI) in patients with type 2 diabetes 5.
- The addition of pioglitazone to sulfonylurea therapy has been found to result in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels compared to metformin plus sulfonylurea 6.
Considerations for Changing Metformin Order
- The patient's current fasting blood glucose level of 174 may indicate that the metformin dose needs to be adjusted or that additional therapy is required.
- Considering the patient's current therapy and the available evidence, adding pioglitazone to metformin or adjusting the metformin dose may be options to improve glycemic control 5, 6, 7, 8.
- However, the decision to change the metformin order should be based on a comprehensive evaluation of the patient's individual needs and medical history.