Are Sulfonylurea and Insulin Therapies Associated With a Larger Risk of Cancer Than Metformin Therapy? A Retrospective Database Analysis

OBJECTIVE Several meta-analyses of observational studies suggested that metformin use reduces cancer risk in type 2 diabetes. However, this result was not confirmed by the few available randomized controlled trials (RCTs), and many observational studies on metformin and cancer were potentially afflicted with time-related bias. We aimed to avoid this bias when comparing cancer incidence in users of sulfonylurea, insulin, and other diabetes medications, respectively, with cancer incidence in metformin users. RESEARCH DESIGN AND METHODS In a retrospective observational study, we used the German Disease Analyzer database with patient data from general practices throughout Germany. The study sample included 22,556 patients diagnosed with type 2 diabetes. During the median follow-up time of 4.8 years, 1,446 (6.4%) patients developed any cancer. In Cox regression analyses with either monotherapies or first diabetes medications as drug exposure, users of sulfonylurea (or insulin or other antidiabetes medications) were compared with metformin users. RESULTS In multivariable adjusted models, hazard ratios were 1.09 (95% CI 0.87-1.36) for sulfonylurea monotherapy, 1.14 (95% CI 0.85-1.55) for insulin monotherapy, and 0.94 (95% CI 0.67-1.33) for other diabetes medications compared with metformin monotherapy. Results were similar for comparison of first diabetes medications. CONCLUSIONS In a retrospective database analysis, taking into account potential time-related biases, no reduced cancer risk was found in metformin users. To clarify the association between diabetes medication and cancer risk, further well-designed observational studies and RCTs are needed.