1. Study identification
EU PAS Register NumberEUPAS3105
Official titleGlargine and risk of cancer
Study title acronymGROC
Study typeObservational study
Brief description of the studyA suspected higher risk of cancer in insulin glargine (IG) than in human insulin (HI) users was investigated in the EGB database, a permanent representative sample of the French national healthcare insurance database, over the period from January 1st, 2003 to June 30th, 2010.
Methods: Cox proportional hazards time-dependent models stratified on the propensity score quartiles for use of IG vs. HI, and adjusted on insulin, biguanide and sulfonylurea possession rates were used to assess the risk of cancer or death in incident or all exclusive or predominant (≥ 80% use time) IG users compared to equivalent HI users.
Results: Only type 2 diabetic patients were studied. Exposures varied from 2273 and 614 patient-years for incident exclusive IG or HI users respectively, to 3125 and 2341 patient-years for all predominant IG or HI users. All-type cancer hazard ratios (HR) with IG vs. HI ranged from 0.59 (95% confidence interval (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 HR for death or cancer associated with IG compared to HI ranged from 0.58 (95%CI 0.32, 1.06) to 0.56 (95%CI 0.36, 0.87).
Conclusion: There was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared to human insulin alone. The overall risk of death or cancer in patients on glargine was about half that of patients on HI, thereby excluding bias from competing risk of death.
Was this study requested by a regulator?Yes: France
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Department/Research grouppharmacoepidemiology
Organisation/affiliationUniversity of Bordeaux
Details of (Primary) lead investigator
Title Dr
Last name Blin
First name Patrick
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
France
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed18/10/2010
Start date of data collection07/12/2010
Start date of data analysis14/02/2011
Date of interim report, if expected
Date of final study report20/09/2011
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesSanofi80
Charities
Government body
Research councils
EU funding scheme
OtherUniversity of Bordeaux20
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Blin
First name Patrick
Address line 1Dept pharmacology - Univ Bordeaux
Address line 2Rue Eugène Jacquet
Address line 3Case 41
CityBordeaux
Postcode33076
CountryFrance
Phone number (incl. country code)33557573747
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Blin
First name Patrick
Address line 1146 Rue Leo Saignat
Address line 2
Address line 3
CityBordeaux
Postcode33076
CountryFrance
Phone number (incl. country code)33557574737
Alternative phone number33557571560
Fax number (incl. country code)33557574671
6. Study drug(s) information
Substance class (ATC Code)A10A (INSULINS AND ANALOGUES)
7. Medical conditions to be studied
Medical condition(s)Yes
Insulin-requiring type 2 diabetes mellitus
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects5000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources not registered with ENCePP
EGB, France
Sources of data
Administrative database, e.g. claims database
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
study the posssible relationship between exposure to insulin glargine and the diagnosis of cancer
Are there primary outcomes?Yes
registration for a diagnosis of cancer in diabetic patients using insulin
Are there secondary outcomes?Yes
relationship with duration and intensity of exposure (medication possession rates) to insulin, sulfonylureas and metformin.
incidence rates for individual cancer types.
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
Cox time-dependent risk ratio and survival analysis of cancer adjusted for propensity score for exposure to human insulin vs glargine, in various user cohorts: incident exclusive users, all exclusive users, incident predominant users, all predominant users.