Optimizing metformin therapy in practice: Tailoring therapy in specific patient groups to improve tolerability, efficacy and outcomes
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Abstract Metformin is the first‐line medication for type 2 diabetes. It is effective and safe, provided some caution is taken in specific populations. In patients with chronic kidney disease, metformin may provide long‐term benefits, and it is a first‐line therapy for diabetes, but the estimated glomerular filtration rate (eGFR) must be assessed regularly, to minimize the risk for metformin accumulation. When eGFR is 30‐60 mL/min/1.73m 2 , the dose should be reconsidered, and sick‐days education provided. Metformin should be discontinued when eGFR falls below 30 mL/min/1.73m 2 . Metformin accumulation may increase the risk for lactic acidosis if concomitant risk factors for hyperlactataemia (liver or respiratory insufficiency, sepsis, acute heart failure) are present; in these conditions, metformin is contraindicated, even although the available evidence is reassuring. Patients on metformin often complain of gastrointestinal side effects (mainly diarrhoea and nausea) during therapy initiation, but they may sometimes occur after years of stable therapy. These usually resolve if the dose is carefully titrated, or by switching to the extended‐release formulation. Patients with obesity may benefit from the significant, although modest, metformin‐associated weight loss and appetite reduction. During pregnancy, metformin is associated with a reduction of pregnancy complications, especially in obese women, but some concern remains, because metformin crosses the placenta, and it is associated with a significantly lower mean birth weight than insulin. In the elderly, gastrointestinal tolerability and renal function must be reassessed more often. Vitamin B‐12 should be screened regularly in long‐time metformin users because metformin may induce clinical vitamin B‐12 deficiency.
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Sulfonylureas are inexpensive and have high HbA1C-lowering efficacy.
“Sulfonylureas are inexpensive and have high HbA1C-lowering efficacy.38,81”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [81]
Section 7 (Managing metformin in the elderly; page unavailable) describes sulphonylureas as having efficacy similar to metformin, supporting their glucose-lowering efficacy, but does not characterize their HbA1c-lowering efficacy as high. The Introduction says metformin has a very low cost; it does not say sulphonylureas are inexpensive. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Authors
- Silverii, G. A.
- Affiliations
- University of Florence (IT)
- Corresponding author
- Silverii, Giovanni Antonio
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2024-07-10
- Volume
- 26
- Issue
- S3
- Pages
- 42-54
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W4400569755
- Cited by
- 33
- References
- 136
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 2
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metformin, type 2 diabetes, chronic kidney disease, estimated glomerular filtration rate, lactic acidosis, hyperlactatemia, gastrointestinal tolerance, extended-release metformin, obesity, weight loss, pregnancy, birth weight, vitamin B12 deficiency, elderly patients, dose titration
- MeSH terms
- Acidosis, Lactic, Diabetes Mellitus, Type 2, Female, Glomerular Filtration Rate, Humans, Hypoglycemic Agents, Male, Metformin, Obesity, Pregnancy, Treatment Outcome, Renal Insufficiency, Chronic
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