Thiazolidinedione and sulfonylureas have similar CV benefit for diabetics on top of metformin
Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trialLiterature - Vaccaro O, Masulli M, Nicolucci A, et al. - Lancet Diab Endocrinol 2017
- The primary CV composite outcome occurred in 7% of patients in the pioglitazone group, and in 7% of patients in the group of sulfonylureas, corresponding to 1.5 per 100 person-years (PY) in both groups. There were no significant between-group differences in the composite primary outcome (HR: 0.96; 95% CI: 0.74 – 1.26; P = 0.79) or in its components.
- The key secondary outcome occurred in 5% of patients in the pioglitazone group, corresponding to 1.1 per 100 PY, and in 6% of patients in the sulfonylureas group, corresponding to 1.2 per 100 PY (HR: 0.88; 95% CI: 0.65 – 1.21; P = 0.44).
- HF occurred in 1% of patients in the pioglitazone group and in 1% of patients in the sulfonylureas group (HR: 1.57; 95% CI: 0.76 – 3.24; P = 0.22).
- The mean HbA1c over time was slightly lower for patients in the pioglitazone group than for patients in the sulfonylureas group (7.24%; SD: 0.20; vs 7.30%; SD: 0.21; P = 0.01; 55 mm/mol vs 56 mmol/mol).
- Fewer patients had treatment failure with pioglitazone compared with sulfonylureas (13% vs 20%; HR: 0.63; 95% CI: 0.52 – 0.75; P < 0.0001).
- The overall incidence of serious adverse events was similar in the pioglitazone and sulfonylureas groups. Severe hypoglycemic events were uncommon, but were more frequent with sulfonylureas. The occurrence of confirmed malignant neoplasms, including bladder cancer, was also similar between groups, as well as the incidence of pathological bone fractures and macular edema.
In a real world clinical setting, both sulfonylureas and pioglitazone have a similar effect as add-on therapies to metformin regarding the incidence of total CV events in diabetic patients. These findings suggest that in T2DM patients without CV diseases, pioglitazone or a sulfonylurea are suitable alternatives as add-on treatment to metformin, although the combination of metformin and pioglitazone was advantageous in terms of durability of glycemic control and frequency of hypoglycemia.