Is there a relationship between cancer-related mortality and treatments for type 2 diabetes mellitus?
Bottom Line:
Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk.
Reference:
Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29:254-58.
Study Design:
Cohort (retrospective)
Synopsis:
Insulin resistance and the resulting hyperinsulinemia has been linked to a number of disorders, especially, of course, to type 2 diabetes mellitus. The sequela of the metabolic syndrome are also a consequence, and there is some evidence that cancer is related. Insulin and insulin-like growth factor are required at all stages of cell growth, cancerous or not. Data from the United Kingdom Prospective Diabetes Study (UKPDS) suggest the possibility of an increase in all-cause mortality for patients with type 2 diabetes treated with insulin. The researchers conducting this provocative study identified 10,309 new users of metformin or sulfonylureas in Canada using a drug plan database. They monitored the patients for an average 5.4 years using a computerized vital statistics file. All patients were followed up. The patients were an average 63.4 years old, and 55% were men. In this type of study, no intervention particular to the study was performed; the patients were treated by their individual physicians as they saw fit and the outcomes of the patients were determined over time. Since the patients were not specifically assigned to therapy, imbalances could have (and did) occur. The average age of the patients who were started on a sulfonylurea was 5 years older than the metformin-treated patients (66.9 years vs 61.8 years; P < .0001). A greater proportion of men were in the sulfonylurea group (58.6% vs 53.5%; P <.0001) and more patients initially started on metformin eventually were given insulin (16.3% vs 9.2%; P < .0001). All of these imbalances can be adjusted statistically, though an ideal study would randomly assign patients to prevent such imbalances. A total of 407 cancer-related deaths (3.9%) occurred in the whole group. Before statistical adjustment, 3.5% of patients receiving metformin died of a cancer-related illness compared with 4.9% patients in the sulfonylurea-treated group (P = .001). After statistical adjustment, deaths were still 30% higher in the group treated with a sulfonylurea than in the group taking metformin (hazard ratio [HR] = 1.3; 95% CI, 1.1 - 1.6; P = .012). In addition, cancer-related mortality was almost twice as high in patients treated with insulin, regardless of other treatment (HR = 1.9; 1.5 - 2.4).
