Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight

Sivitz, William I.; Phillips, Lawrence S.; Wexler, Deborah J.; Fortmann, Stephen P.; Camp, Anne W.; Tiktin, Margaret; Perez, Magalys; Craig, Jacqueline; Hollander, Priscilla; Cherrington, Andrea; Aroda, Vanita R.; Tan, Meng H.; Krakoff, Jonathan; Rasouli, Neda; Butera, Nicole M.; Younes, Naji

doi:10.2337/dc19-1769

Cited by 17 publications

(9 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The efficacy of metformin is dose-dependent [ 19 , 21 ], with maximal benefits observed at the upper limits of the recommended daily dosage [ 21 - 23 ] and a minimum fully effective dose of 1.5 g/day [ 22 ]. Nevertheless, the real-world dosage patterns of metformin have been so far poorly investigated [ 10 , 11 ], particularly in the elderly.…”

Section: Discussionmentioning

confidence: 99%

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy

Castellano

Giorgio

Roberto³

et al. 2023

EMIDDT

View full text Add to dashboard Cite

Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients. Methods: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi). Results: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63.4%). As compared to the youngest, participants older than 75 years did not differ for metformin daily dose or number of administrations. Metformin dose was significantly directly correlated to eGFR, diabetes duration, and metformin treatment duration. Conclusion: In this real-world study, the minimum daily effective dose of metformin was prescribed in more than half of older T2DM outpatients.

show abstract

Section: Discussionmentioning

confidence: 99%

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy

Castellano

Giorgio

Roberto³

et al. 2023

EMIDDT

View full text Add to dashboard Cite

show abstract

“…These observations corroborate the previous study findings indicating effectiveness of high-dose metformin in achieving HbA1c reduction and weight reduction. 11 , 24 The landmark UK Prospective Diabetes Study (UKPDS) evaluated a median daily metformin dose of 2550 mg/day in people with newly diagnosed T2DM and reported a median HbA1c of 7.4% compared with 8.0% in the conventional group. 8 In the Diabetes Prevention Program study, during the unblinded follow-up, weight loss was significantly greater in the metformin group compared to the placebo group (−2.0 vs −0.2%, P < .001).…”

Section: Discussionmentioning

confidence: 99%

Real-World Clinical Experience on the Usage of High-Dose Metformin (1500-2500 mg/day) in Type 2 Diabetes Management

Das

Shah²,

Singh³

et al. 2021

Clin Med Insights Endocrinol Diabetes

View full text Add to dashboard Cite

Background: To evaluate the clinical characteristics, treatment patterns, and clinical effectiveness and safety of high doses of metformin (1500-2500 mg/day) in Indian adults with type 2 diabetes mellitus (T2DM). Materials and methods: A retrospective, multicentric (n = 241), real-world study included patients with T2DM (aged >18 years) receiving high doses of metformin. Details were retrieved from patient’s medical records. Results: Out of 5695 patients, 62.7% were men with median age was 50.0 years. Hypertension (67.5%) and dyslipidemia (48.7%) were the prevalent comorbidities. Doses of 2000 mg (57.4%) and 1500 mg (29.1%) were the most commonly used doses of metformin and median duration of high-dose metformin therapy was 24.0 months. Metformin twice daily was the most frequently used dosage pattern (94.2%). Up-titration of doses was done in 96.8% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.08%; P < .001). The target glycemic control was achieved in 91.2% patients. A total of 83.0% had decreased weight. Adverse events were reported in 156 patients. Physician global evaluation of efficacy and tolerability showed majority of patients on a good to excellent scale (98.2% and 97.7%). Conclusion: Clinical effectiveness and safety of a high-dose metformin was demonstrated through significant improvement in HbA1c levels and weight reduction.

show abstract

“… 24 While 2500 mg is considered the maximum dose of metformin, most providers will prescribe up to 2000 mg daily because increasing the dose from 2000 mg to 2500 mg had minimal impact on HbA1c with a slight increase in adverse events. 24 A recent study showed that optimizing metformin to the 2000 mg daily or the maximum tolerated lower dose improves glycemia in type 2 diabetes, 25 confirming that the efficacy of metformin is dose dependent.…”

Section: Metformin: Clinical Use In Type 2 Diabetesmentioning

confidence: 97%

Should metformin remain the first-line therapy for treatment of type 2 diabetes?

Baker

Retzik-Stahr

Singh

et al. 2021

Therapeutic Advances in Endocrinology

Self Cite

View full text Add to dashboard Cite

Metformin is a biguanide that is used as first-line treatment of type 2 diabetes mellitus and is effective as monotherapy and in combination with other glucose-lowering medications. It is generally well-tolerated with minimal side effects and is affordable. Although the safety and efficacy of metformin have been well-established, there is discussion regarding whether metformin should continue to be the first choice for therapy as other anti-hyperglycemic medications exhibit additional advantages in certain populations. Despite a long-standing history of metformin use, there are limited cardiovascular outcomes data for metformin. Furthermore, the available studies fail to provide strong evidence due to either small sample size or short duration. Recent data from glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter-2 inhibitor cardiovascular and renal outcomes trials demonstrated additional protection from diabetes complications for some high-risk patients, which has impacted the guidelines for diabetes management. Post-hoc analyses comparing hazard ratios for participants taking metformin at baseline versus not taking metformin are inconclusive for these two groups. There are no data to suggest that metformin should not be initiated soon after the diagnosis of diabetes. Furthermore, the initiation of newer glycemic-lowering medications with cardiovascular benefits should be considered in high-risk patients regardless of glycemic control or target HbA1c. However, cost remains a major factor in determining appropriate treatment.

show abstract

Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight

Cited by 17 publications

References 34 publications

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy

Real-World Clinical Experience on the Usage of High-Dose Metformin (1500-2500 mg/day) in Type 2 Diabetes Management

Should metformin remain the first-line therapy for treatment of type 2 diabetes?

Contact Info

Product

Resources

About