Acute myopathy in a type 2 diabetic patient on combination therapy with metformin, fenofibrate and rosiglitazone.
OBJECTIVE
This report describes the case of a 75-year-old male type 2 diabetic Caucasian who was admitted to the clinical ward because of acute pain and cramps in both calf muscles.


METHODS
Neuromuscular function was assessed by electromyography and electroneurography of the right leg. An open biopsy was taken from the left vastus lateralis muscle for histological and histochemical analyses. Southern blotting was performed to detect defects in mitochondrial DNA and tRNA. Cytochrome P450 (CYP-P450) polymorphisms were analysed in blood cells.


RESULTS
Fifteen weeks before admission, the patient's lipid-lowering medication was switched from simvastatin to fenofibrate because of predominant hypertriglyceridaemia; this did not affect creatine kinase levels. Three weeks before admission, rosiglitazone was added to his existing metformin therapy because of worsening metabolic control. Upon admission, serum enzymes indicating myopathy were elevated (creatine kinase 6897 U/l, myoglobin 902 ng/ml) and kidney function was impaired (creatinine 0.116 mmol/l, blood urea nitrogen 2.3 mmol/l). Electrophysiology revealed myopathy and sensory polyneuropathy. Histology showed multiple damage of the myofibrillar architecture. There was no evidence of defects in mitochondrial DNA or tRNA. Furthermore, no functional limitations in CYP2C9, CYP2C19 and CYP2D6 were detected. Following withdrawal of the oral medication and intravenous hydration, clinical symptoms and laboratory parameters gradually decreased.


CONCLUSIONS
Until more data from controlled trials are available, we recommend that combination therapy with fibrates and thiazolidinediones should be monitored frequently by measurements of serum creatine kinase and creatinine, specifically in patients with pre-existing nephropathy and polyneuropathy.
Ledl
M
M
First Medical Department, Hanusch Hospital, Heinrich Collin Strasse 30, A-1140, Vienna, Austria.
Hohenecker
J
J
Francesconi
C
C
Roots
I
I
Bauer
M F
MF
Roden
M
M
D000368:Aged; D003402:Creatine Kinase / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D004347:Drug Interactions; D004576:Electromyography; D011345:Fenofibrate / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D009135:Muscular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D003402:Creatine Kinase; D011345:Fenofibrate