Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database.
OBJECTIVE
Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010.


METHODS
We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin, and adjusted for insulin, biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant (≥ 80% use time) users of insulin glargine compared with equivalent human insulin users.


RESULTS
Only type 2 diabetic patients were studied. Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin, respectively, to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin, respectively. All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 (95% CI 0.28, 1.25) in incident exclusive users to 0.58 (95% CI 0.34, 1.01) in all predominant users. Cancer risk increased with exposure to insulin or sulfonylureas in these patients. Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 (95% CI 0.32, 1.06) to 0.56 (95% CI 0.36, 0.87).


CONCLUSIONS
There was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone. The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin, thereby excluding a competitive risk bias.
Department of Pharmacology, Bat du Tondu, Case 40, Université de Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux, France.
P
P
Blin
R
R
Lassalle
C
C
Dureau-Pournin
B
B
Ambrosino
M A
MA
Bernard
A
A
Abouelfath
H
H
Gin
C
C
Le Jeunne
A
A
Pariente
C
C
Droz
N
N
Moore
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009026:Mortality; D009313:National Health Programs; D009369:Neoplasms / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D012306:Risk; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D013453:Sulfonylurea Compounds; D000069036:Insulin Glargine; D008687:Metformin