Gliclazide no better than other sulfonylureas as to obesity-related cancer risk

The risk of obesity-related cancer with gliclazide is comparable to that seen with other sulfonylureas, a study has found.

The analysis included 26,207 patients with type 2 diabetes (T2D) who used sulfonylureas, among whom 11,911 (45.4 percent) were new users. In this new-user group, the most common drug used was gliclazide (58.6 percent), and there was a high proportion of active smokers (33.7 percent). Meanwhile, glibenclamide users were the oldest (mean age, 68.3 years), had the lowest mean body mass index (mean, 29.4 kg/m²), and longest diabetes duration (median, 7.1 years).

Overall, there were 1,111 obesity-related cancer events recorded over a median follow-up of 7 years, corresponding to an incidence rate of 663 per 105 person-years. Sulfonylureas showed no significant within-class differences in the risk of overall and site-specific obesity-related cancers.

On Cox regression analyses using gliclazide as reference, the adjusted hazard ratios for obesity-related cancer were 1.10 (95 percent confidence interval [CI], 0.92–2.69) with glibenclamide, 1.13 (95 percent CI, 0.68–1.84) with glimepiride, and 0.93 (95 percent CI, 0.59–1.48) with tolbutamide in men. The corresponding estimates in women were 1.49 (95 percent CI, 0.72–3.13), 0.96 (95 percent CI, 0.59–1.54), and 0.84 (95 percent CI, 0.54–1.28).

The respective risk estimates associated with 1 more year of cumulative exposure to the three sulfonylureas (glibenclamide, glimepiride, and tolbutamide) vs gliclazide were 0.90 (95 percent CI, 0.71–1.14), 0.96 (95 percent CI, 0.87–1.06), and 1.00 (95 percent CI, 0.92–1.09) in males; and 0.93 (95 percent CI, 0.77–1.13), 0.99 (95 percent CI, 0.90–1.10), and 1.04 (95 percent CI, 0.96–1.13) in females.

Gliclazide is the preferred sulfonylurea in two guidelines of T2D management, based on evidence that it is associated with the lowest incidence of hypoglycaemic events and a putatively favourable cardiovascular safety profile, the researchers noted. However, the results suggest that the drug is not superior to others in the same class in terms of obesity-related cancer risk. [Huisarts Wet 2013;56:512-525]