Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease. Stable glycemic control is critical not only for quality of life—including daily energy, appetite, and sleep—but also for preserving islet function and preventing long-term complications.
As the 2026 American Diabetes Association (ADA) guidelines further expand the eligible population for continuous glucose monitoring (CGM), precise evaluation of glycemic fluctuations and optimized glycemic control have become core goals in diabetes clinical practice.
However, most existing CGM-based research data have been derived from the field of insulin therapy.
Moreover, although dipeptidyl peptidase-4 inhibitors (DPP-4i) are widely used in diabetes management, it remains unclear whether different dosing frequencies—biweekly vs. daily formulations—lead to differences in glycemic stability.
Against this background, a team led by Professor Chen Liming from the Zhu Xianyi Memorial Hospital of Tianjin Medical University conducted a clinical study on switching from daily DPP-4i to biweekly dorzagliatin.
Leveraging the precision of CGM technology, the study comprehensively compared the glycemic control efficacy and patient treatment satisfaction between the two regimens.
This was a multicenter, randomized, open-label, prospective study, consisting of a 3-week screening period, a 24-week open-label treatment period, and a 2-week safety follow-up period.
A total of 64 adult patients with T2DM were enrolled and randomized 1:1 to the dorzagliatin group (31 patients) and the daily DPP-4i group (33 patients).
Inclusion criteria:
Patients who had received stable treatment with a daily DPP-4i, alone or in combination with metformin (1500 mg/day or maximum tolerated dose of 1000–1500 mg/day) for 12 weeks before screening, with an estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73m².
CGM was performed for 14 consecutive days at three time points:
0–2 weeks (baseline), 10–12 weeks, and 22–24 weeks, for precise assessment of glycemic control.
Primary endpoint:
Change in time in range (TIR) from baseline to week 24, defined as the change in the percentage of time glucose was within the target range of 3.9–10.0 mmol/L over a 2-week period.
Secondary endpoints:
Time above range (TAR, >10.0 mmol/L), time below range (TBR, <3.9 mmol/L), mean glucose (MG), largest amplitude of glycemic excursion (LAGE), mean amplitude of glycemic excursion (MAGE), coefficient of variation (CV), etc.
Daily DPP-4i was chosen as the comparator for a key reason:
dorzagliatin and daily DPP-4i belong to the same class of agents, with identical mechanisms of action, differing only in formulation and dosing frequency (dorzagliatin is biweekly, while comparators are daily).
This ensures high comparability.
Comparing drugs with different mechanisms would greatly reduce the validity of results, making it difficult to accurately determine whether biweekly formulations achieve efficacy equivalent to daily ones, or whether plasma concentration fluctuations might cause unstable glucose levels.
Compared with the daily DPP-4i group, the biweekly dorzagliatin group showed a significant advantage in the primary endpoint:
- The least-squares (LS) mean change in TIR from baseline to week 24 was 0.037% in the dorzagliatin group
- vs. −9.891% in the daily DPP-4i group
The between-group difference in LS means was 9.929% (95% CI: 3.064%–16.793%), which was statistically significant (P = 0.0046).
For secondary endpoints, dorzagliatin also performed significantly better:
TAR, MG, LAGE, MAGE, standard deviation (SD) of glucose, and CV all improved significantly from baseline and were superior to the daily DPP-4i group (all P < 0.01).
This confirmed that despite less frequent dosing, dorzagliatin provided better glycemic stability than daily DPP-4i.
Subgroup analyses showed that the LS mean increase in TIR from baseline to week 24 was significantly greater in the dorzagliatin group among patients with:
- HbA1c ≥ 7%,
- age ≥ 60 years,
- female sex,
- BMI ≥ 24 kg/m²,
- and background therapy including metformin (all P < 0.05).
In addition, systematic assessment using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) showed that biweekly dorzagliatin was significantly superior in six core dimensions:
- current treatment satisfaction,
- convenience,
- flexibility,
- understanding of diabetes knowledge,
- willingness to recommend,
- willingness to continue treatment.
Improvements in hypoglycemia tolerance scores also reached statistical significance.
Regarding safety:
The incidence of adverse events was similar between the dorzagliatin group and the daily DPP-4i group (64.5% vs. 69.7%), with mostly mild events and low hypoglycemia risk.
Notably, the dorzagliatin label clearly states its suitability for patients with renal insufficiency or mild hepatic impairment, eliminating safety concerns in special populations.
In conclusion:
Dorzagliatin administered once every two weeks reduces dosing frequency from 365 to 26 times per year compared with daily DPP-4i.
It provides more stable glycemic control, higher treatment satisfaction, and better medication adherence, while maintaining a favorable safety profile.