Risk of lactic acidosis associated with metformin use in patients with type 2 diabetes and moderate-severe chronic kidney disease: a case-control study (ALIMAR-C2)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10BA02) metformin

  metformin

  (A10BD03) metformin and rosiglitazone

  metformin and rosiglitazone

  (A10BD05) metformin and pioglitazone

  metformin and pioglitazone

  (A10BD07) metformin and sitagliptin

  metformin and sitagliptin

  (A10BD08) metformin and vildagliptin

  metformin and vildagliptin

  (A10BD10) metformin and saxagliptin

  metformin and saxagliptin

  (A10BD11) metformin and linagliptin

  metformin and linagliptin
• Medical condition to be studied:
  Lactic acidosis

  Chronic kidney disease

  Type 2 diabetes mellitus

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Renal impaired
• Estimated number of subjects:
  147

Study design details

• Main study objective:
  To assess the association between use of metformin and lactic acidosis (LA) in patients with type 2 diabetes (2D) and moderate to severe chronic kidney disease (CKD).
• Outcomes:
  Occurrence of lactic acidosis. Case fatality rate.
• Data analysis plan:
  Logistic regression will be used to estimate the crude and adjusted risk of LA associated to metformin overall and stratifying by dose and use categories and CKD stage. Covariables will include: age, sex, Charlson’s comorbidity index, diabetic complications, liver disease, myocardial infarction, heart failure, acute renal failure, seizures, dehydration, gastroenteritis, shock, sepsis, respiratory failure, exposure to other antidiabetics, insulin, diuretics, RAS inhibitors, or NSAIDs, and others. The crude and adjusted risk of LA associated to other antidiabetics and insulin use will be also estimated. Sensitivity analyses will be performed to assess the homogeneity of data from different geographic regions and to exclude patients with missing covariables. The case fatality rate will be calculated as the proportion of patients dead during hospitalization. Observation bias will be analyzed by means of the frequency of lactate determination depending on the use of metformin.