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TOPLINE
Adding teneligliptin, a DPP-4 inhibitor, to metformin and empagliflozin lowered A1c by 0.67% more than placebo at 24 weeks in patients with poorly controlled type 2 diabetes (T2D). The benefit held through 52 weeks with no new safety concerns.
METHODOLOGY
- SGLT2 inhibitors such as empagliflozin cause glucosuria, which appears to raise endogenous glucose production and may blunt about half of their glucose-lowering effect. DPP-4 inhibitors such as teneligliptin may counter this by boosting incretin action, which reduces the secretion of glucagon.
- Researchers conducted a phase 3 trial in South Korea that included 214 patients with T2D (mean age, 57.07 years; 58.88% men) who had poorly controlled blood sugar on metformin (≥ 1000 mg/d) plus empagliflozin (25 mg/d). They were randomly assigned in a 1:1 ratio to once-daily teneligliptin 20 mg or matching placebo for 24 weeks.
- Patients who completed the 24-week period and consented to continue entered a 28-week open-label extension, in which everyone, including those initially assigned to placebo, received teneligliptin 20 mg/d.
- The primary endpoint was the change in A1c level from baseline to week 24. Safety was assessed through week 52.
- At 24 weeks, 105 patients (98.13%) in the teneligliptin group and 100 (93.46%) in the placebo group had completed the main treatment. At 52 weeks, 102 (95.33%) in the teneligliptin group and 93 (86.92%) in the placebo group had completed the 28-week extension.
TAKEAWAY
- At week 24, the least squares mean change in A1c from baseline was -0.70% with teneligliptin and -0.03% with placebo, with a placebo-adjusted difference of -0.67% (P < .0001). The difference was significant as early as week 4 (placebo-adjusted, -0.36%; P < .0001) and the A1c reduction in the teneligliptin group was maintained through week 52.
- At week 24, teneligliptin lowered fasting plasma glucose by 12.73 mg/dL more than placebo and raised the homeostasis model assessment of beta-cell function by 10.36 more (P < .05 for both). Both gains persisted through week 52 in the teneligliptin group.
- Patients who switched from placebo to teneligliptin after week 24 experienced an A1c reduction of 0.66% and a fasting glucose drop of 8.62 mg/dL (P < .05 for both).
- During the first 24 weeks, one patient (0.93%) on teneligliptin and four patients (3.74%) on placebo had serious adverse events; none were considered to be related to the study drug. Extended treatment through 52 weeks raised no new safety concerns, and no patient had severe hypoglycemia.
IN PRACTICE
"These findings support its use in patients with T2DM [T2D] inadequately controlled with metformin and empagliflozin," the authors wrote.
SOURCE
The study was led by Jun Sung Moon, Yeungnam University College of Medicine, Daegu, South Korea. It was published online on October 5, 2026, in Diabetes, Obesity and Metabolism.
LIMITATIONS
The blinded, placebo-controlled phase lasted only 24 weeks; therefore, later results came from an open-label period rather than continued randomization. All participants were Korean adults, which limited generalizability to other ethnic groups and populations. The trial did not collect continuous glucose monitoring data or patient-reported outcome measures.
DISCLOSURES
The trial was funded by Handok Inc., Seoul, South Korea. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
