β-Cell Recovery Patterns With Initial Combination Versus Stepwise Therapy in Newly Diagnosed Type 2 Diabetes: TRIPLE-AXEL Post Hoc Analysis.

Authors

Il Rae Park, Jun Sung Moon, Joon Ha, Eunvin Ko, Yong-Ho Lee, Ho Chan Cho, Soo Heon Kwak, Soo Lim, Min Kyong Moon, Dong-Lim Kim, Tae Ho Kim, Sin Gon Kim, Nam Hoon Kim

Published in

Diabetes, obesity & metabolism. Nov 03, 2026. Epub Nov 03, 2026.

Abstract

Early intensive therapy may preserve β-cell function in newly diagnosed Type 2 diabetes mellitus (T2DM), but whether different early treatment strategies produce distinct patterns of β-cell functional recovery remains unclear.
This post hoc analysis of the TRIPLE-AXEL trial included 75 drug-naïve participants who completed 104 weeks of treatment and underwent 75-g oral glucose tolerance tests at baseline and Week 104. Participants were randomized to initial triple combination therapy (TCT; metformin, dapagliflozin and saxagliptin) or stepwise add-on therapy (SAT; metformin followed by glimepiride and sitagliptin). Insulin secretion, insulin sensitivity and β-cell compensatory function were assessed using the insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI) and disposition index (DI), respectively.
HbA1c decreased by approximately 2.7% over 104 weeks in both groups. DI increased significantly in both TCT and SAT, with no significant between-group difference in the baseline-adjusted change (difference, -0.09 [95% CI, -0.44 to 0.27]; p = 0.63). Baseline-adjusted changes in IGI and ISI also did not differ significantly between groups (p = 0.35 and p = 0.85, respectively), although the within-group increase in ISI was significant only in the TCT group. In multivariable models, greater HbA1c reduction was associated with higher DI at Week 104. Hypoglycaemia occurred in none of the participants in the TCT group and in 23.7% of those in the SAT group.
In newly diagnosed T2DM, both treatment strategies improved β-cell function without significant between-group differences. TCT achieved this without hypoglycaemia; however, given the on-treatment assessment, physiological equivalence cannot be concluded.
ClinicalTrials.gov identifier: NCT02946632.

PMID:
42977550
Bibliographic data and abstract were imported from PubMed on 04 Nov 2026.

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