Metformin discontinuation effects
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Metformin Discontinuation Effects on Cardiovascular, Renal, and Mortality Outcomes
Discontinuing metformin in patients with type 2 diabetes, especially those with advanced chronic kidney disease (CKD), is linked to higher risks of major adverse cardiovascular events (MACE), heart failure, end-stage kidney disease (ESKD), and death. Large cohort studies show that patients who stopped metformin after their estimated glomerular filtration rate (eGFR) dropped below 30 ml/min/1.73m² had significantly higher rates of these complications compared to those who continued metformin, regardless of their cardiovascular disease history 14. These findings suggest that continuing metformin, even at lower eGFR levels, may offer cardio-renal and survival benefits, though the risk of lactic acidosis must still be considered 14.
Glycemic Control, Weight, and Hypoglycemia After Metformin Discontinuation
When metformin is discontinued, patients often experience a rise in blood sugar (HbA1c) levels, at least in the short term 42. Providers typically respond by increasing doses of other diabetes medications, such as insulin or sulfonylureas, which can restore glycemic control but also lead to significant weight gain and a higher risk of hypoglycemia 27. The cost of therapy also increases, as alternative medications are often more expensive than generic metformin . Some studies found that glycemic control could be maintained after discontinuation, but this often required more aggressive medication adjustments and was associated with further declines in kidney function .
Predictors and Patterns of Metformin Discontinuation
Metformin is commonly discontinued in older patients and those with a history of chronic kidney disease, especially when starting second-line diabetes therapies . Rapid dose escalation, higher fasting blood sugar, and higher body mass index (BMI) are also linked to a greater likelihood of stopping metformin due to side effects, particularly gastrointestinal issues like diarrhea . Women are more likely than men to discontinue metformin because of side effects .
Metformin Discontinuation and Imaging Procedures
Short-term discontinuation of metformin (24–48 hours) before certain imaging procedures, such as FDG PET/CT scans, significantly reduces intestinal uptake of the imaging agent, improving scan interpretation 56. A 48-hour discontinuation is more effective than 24 hours for reducing bowel activity, but may cause a temporary increase in blood glucose levels 56.
Effects on Weight and Metabolic Health After Discontinuation
In patients with schizophrenia treated with clozapine, metformin helps reduce body weight and improve metabolic health. However, these benefits are lost after stopping metformin, with body weight returning to baseline . Similarly, in a preclinical model of postmenopausal breast cancer, stopping metformin after a period of use led to weight gain, increased adiposity, and worsened metabolic markers, all of which are linked to higher cancer risk .
Conclusion
Discontinuing metformin, especially in patients with diabetes and CKD, is associated with increased risks of cardiovascular and renal complications, higher mortality, weight gain, more hypoglycemia, and higher treatment costs. While short-term discontinuation may be necessary for certain imaging procedures, long-term discontinuation should be carefully considered, weighing the potential risks and benefits for each patient. Maintaining metformin therapy, when safe, appears to offer important protective effects for both metabolic and cardiovascular health.
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