Metformin in Moderate and Severe Renal Failure (CKD 3-4): A Follow-up Study (METsuiviIRC)

Centre Hospitalier Universitaire, Amiens

Status and phase: Withdrawn; Phase 2

Conditions: Renal Insufficiency, Chronic

Treatments: Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT02848508

PI2016_843_0009

Details and patient eligibility

About

To validate on the mid-term in moderate and severe renal failure (CKD 3-4) a nomogram to adapt a fixed metformin daily posology according to renal function on the basis of the first short-term study made by the investigators.

Full description

A first open-label pilot study at different stages of CKD (1-5) (concerning whether or not metformin use is safe provided a dose adjustment is used) has evaluated (i) metformin levels in plasma and in erythrocytes according to an increasing metformin dosage and CKD severity (1-5) and (ii) the prevalence of lactate levels ≥2.5 mmol/L in CKD 3-5. All patients underwent 3 one-week- blocks of metformin treatment at an increasing dosage, each of which followed by a one week-wash- out period: 500 mg/day in the evening (E) in phase 1; 1,000 mg/day (500 mg morning (M) and E) in phase 2; 2,000 mg/day (1,000 mg M and E) in phase 3.

Steady-state trough blood levels were assayed 12 hours after the last dose of metformin. In this study a progressive dose-related increase of the trough metformin levels were observed and in particular in severe CKD stages. No case of severe hyperlactatemia was reported in this study. In continue, the investigators thought to conduct a new study to evaluate safety of metformin in mid-term period of time. For this purpose, metformin will be given at a fixed dose during 4 months: 1) 1,500 mg/day (500 mg M and 1,000 mg E) in stage 3a; 2) 1,000 mg/day (500 mg M and E) in stage 3b; and 3) 500 mg/day (M) in stage 4. Metformin levels in plasma and in erythrocytes, venous lactate, and HbA1c levels will be measured at 1, 2, 3 and 4 months for assessment of safety.

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 diabetes patients with stable CKD stages 3A, 3B and 4 aged between 18 and 80 years requiring metformin (and any other antidiabetic treatment)

Exclusion criteria

• Hyperlactatemia (> 2.5 mmol/L)
• No creatinine levels available since 3 months
• Severe hepatic insufficiency
• No liver function parameters available
• Need of investigation with iodized contrast media
• Hypersensitivity to metformin

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

moderate impairment, CKD stage 3a

Experimental group

Description:

(12 subjects): GFR 59-45 (moderate impairment, CKD stage 3a) Metformin : 1500mg/day

Treatment:

Drug: Metformin

moderate impairment, CKD stage 3a)

Experimental group

Description:

(12subjects): GFR 44-30 (moderate impairment, CKD stage 3b) Metformin : 1000mg/day

Treatment:

Drug: Metformin

severe impairment

Experimental group

Description:

(12 subjects): GFR 29-15 (severe impairment, CKD stage 4) Metformin : 500mg/day

Treatment:

Drug: Metformin