Ertugliflozin noninferior to glimepiride in reducing HbA1c
Ertugliflozin 15 mg once daily is noninferior to the sulphonylurea glimepiride in HbA1c reduction over 52 weeks in patients with type 2 diabetes (T2D) who are inadequately controlled on metformin, according to the VERTIS* SU trial presented at EASD 2017 in Lisbon, Portugal.
Along with a lower HbA1c, ertugliflozin also resulted in greater body weight reductions and less hypoglycaemia, but more genital mycotic infections than glimepiride, revealed study senior investigator Dr Brett Lauring from Kenilworth, New Jersey, US.
“[Although] sulphonylureas are commonly used in patients with T2DM as second-line therapy… [they] are associated with an increased risk of hypoglycaemia and weight gain,” he continued. “Ertugliflozin improves glycaemic control via an insulin-independent mechanism that poses a low risk for hypoglycaemia.”
After 52 weeks, ertugliflozin 15 mg was noninferior to glimepiride in lowering HbA1c from baseline (least square [LS] mean difference, -0.6 vs -0.7). Although the lower-dose 5 mg ertugliflozin arm also showed similar HbA1c reduction, this did not reach noninferiority compared with glimepiride. [EASD 2017, abstract OP #38]
Fewer patients in both the ertugliflozin arms than the glimepiride arm experienced symptomatic hypoglycaemia (5.2 percent and 3.1 percent, vs 19.2 percent for ertugliflozin 15 mg and 5 mg vs glimepiride, respectively; p<0.001 for both comparisons), with the ertugliflozin 15 mg arm showing a significantly greater reduction in FPG** through 52 weeks from baseline compared with the glimepiride arm (LS mean, -1.3 vs -0.9; p<0.001).
Also, significantly greater reductions in body weight were seen with ertugliflozin vs glimepiride (LS mean, -3.4 and -3.0, vs 0.9; p<0.001).
Additional key secondary measure such as systolic blood pressure reductions from baseline were greater with ertugliflozin than with glimepiride through 52 weeks (mean LS, -3.8 and -2.2, vs 1.0 mm Hg; p<0.001).
“Ertugliflozin is an orally administered, potent, highly-selective SGLT2* inhibitor … currently under US and EU regulatory reviews for treatment of T2D,” said Lauring.
However, mycotic genital infections occurred more frequently in both the ertugliflozin arms than the glimepiride arm, regardless of gender (female: 10.0 percent and 7.7 percent vs 1.4 percent; p<0.001 and p=0.002 for each comparison, and male: 2.1 percent and 4.4 percent vs 0 percent; p=0.03 and p=0.002 for each comparison).
Other prespecified adverse events (AEs) such as urinary tract infection (UTI) and hypovolaemia occurred at comparable rates among the treatment groups.
“Ertugliflozin 5 mg and 15 mg were generally well tolerated, without a meaningful difference in the incidence of UTI or hypovolaemia AEs,” observed Lauring.
The double-blind phase III trial randomized 1,326 patients with HbA1c 7.0–9.0 percent who were on metformin ≥1,500 mg/day in a 1:1:1 ratio to ertugliflozin 15 mg or 5 mg, or glimepiride for 52 weeks.In general, similar incidence of drug-related AEs was reported across treatment groups (21.6 percent and 18.3 percent, vs 17.8 percent), with comparable rates of AEs leading to discontinuation (5.7 percent and 4.0 percent, vs 3.9 percent). Rates of serious AEs were low (0.7 percent and 0 percent, vs 0.2 percent). One and five deaths were reported in the ertugliflozin 15 mg and 5 mg arms, respectively vs one death in the glimepiride arm, but none was considered to be related to the study drugs, according to the investigators.