Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy.

INTRODUCTION: Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. METHODS: In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy. Prespecified clinical and biochemical safety endpoints of serum bicarbonate, venous pH, and serum lactate were assessed weekly. Efficacy was assessed by pre- and post-HbA1c and 72-hour capillary glucose monitoring. RESULTS: There was no evidence of accumulation of metformin in any cohort. There were no episodes of hyperlactatemia or metabolic acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts. DISCUSSION: In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing.

Lisfranc fracture-dislocation precipitating acute Charcot arthopathy in a neuropathic diabetic foot: a case report.

The Lisfranc injury is relatively uncommon yet remains popular in the literature due to its variable causative mechanisms and subtleties in radiographic features despite its potential for disabling long term outcomes if treatment is inadequate, inappropriate or delayed. These injuries are especially pertinent in diabetic patients, especially those with neuropathy, since they are more common, can lead to Charcot neuropathic joint, ulcers and have different causative mechanisms compared to the general population. We describe the case of a neuropathic diabetic patient who presented with a Lisfranc injury which precipitated the development of acute Charcot arthropathy in the right foot. The case serves to illustrate several salient points about the Lisfranc joint and related injuries in diabetic patients.