Metformin

Metabolic· 197 cited findings· 1 source document

Company: Takeda Pharmaceutical Company Limited →

What the regulatory reviews say

Metformin is a medication used in patients with type 2 diabetes mellitus (T2DM) and atherothrombosis. In the REACH study, involving 19,691 patients, the adjusted hazard ratio for 2-year overall mortality was 0.76 (95% CI: 0.65-0.89, P-value: <0.01). For the subgroup with GFR 30-60 ml/min/1.73 m2, the adjusted hazard ratio for 2-year mortality was 0.64 (95% CI: 0.48-0.86, P-value: 0.003).

Safety data indicates a crude incidence of lactic acidosis among metformin users of 3.3 cases per 100,000 person-years. This compares to 4.8 cases per 100,000 patient-years in sulphonylurea users. The incidence rate of lactic acidosis in current metformin users varied by GFR: 5.29 cases per 100,000 patient-years for GFR ≥ 60 ml/min, 14.45 cases per 100,000 patient-years for GFR 45-59 ml/min, and 19.65 cases per 100,000 patient-years for GFR 30-44 ml/min. Metformin maximum doses are 2000 mg for CKD stage 1 and 4, and 1000 mg for CKD stage 5.

Regulatory information includes recommended doses for other diabetes medications in renal impairment, such as saxagliptin (2.5 mg once daily), sitagliptin (50 mg once daily), and linagliptin (5 mg daily).

Key figures — cited to the source page

Adjusted hazard ratio for 2-year mortality (overall) in REACH study	0.76	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.12
95% CI for adjusted hazard ratio for 2-year mortality (overall) in REACH study	0.65-0.89	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.12
P-value for adjusted hazard ratio for 2-year mortality (overall) in REACH study	<0.01	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.12
Metformin maximum dose for CKD stage 1 and 4	2000 mg	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.7
Metformin maximum dose for CKD stage 5	1000 mg	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.7
Crude incidence of lactic acidosis among metformin users	3.3 cases per 100,000 person-years	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.15
Incidence of lactic acidosis in sulphonylurea users	4.8 /100,000 patient-years	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.15
Incidence rate of lactic acidosis (current metformin users, GFR 30-44 ml/min)	19.65 cases per 100,000 patient-years	Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR va, p.16

Source documents

Takeda Pharmaceutical Company Limited — Vipdomet EMA EPAR variation assessment report (EMEA/H/C/002654, 2013) (2013)

Explore the full evidence

All 197 cited findings for Metformin — searchable, comparable and answerable in plain language — are in the Metabolic research library →

Figures are as stated in the cited regulatory review documents (different drugs are studied in different trials — values are not head-to-head comparisons). Educational reference only — not medical or investment advice.