AIMS: To compare the glycaemic efficacy, continuous glucose monitoring (CGM) metrics, and safety of biweekly efsubaglutide alfa 3 mg (Q2W) versus weekly 1 mg (QW) in adults with type 2 diabetes inadequately controlled with lifestyle intervention.
MATERIALS AND METHODS: In this multicentre, randomised, open-label trial, 59 adults were allocated 1:1 to efsubaglutide alfa 3 mg Q2W or 1 mg QW for 12 weeks after a 1-week 1 mg run-in. The primary endpoint was change in HbA1c from baseline to week 13 (end of 12-week treatment). Secondary endpoints included fasting plasma glucose (FPG), CGM time in range (TIR, 3.9-10.0 mmol/L) and tight TIR (3.9-7.8 mmol/L), 24-h mean glucose, weight, lipids, and adverse events. Continuous outcomes were analysed using a mixed model for repeated measures (MMRM); categorical outcomes used stratified Mantel-Haenszel tests; p values/CI were descriptive.
RESULTS: HbA1c decreased by -1.45% (SE 0.14) with Q2W and -1.53% (0.14) with QW; LS mean difference (Q2W-QW) 0.09% (95% CI -0.32, 0.50). FPG fell similarly (-2.07 vs. -2.22 mmol/L). TIR increased from 45.0% to 77.2% with Q2W and 75.1% with QW; tight TIR reached 53.8% and 48.8%, respectively. End-of-treatment 24-h mean CGM glucose was 8.12 versus 8.66 mmol/L (Q2W vs. QW). At week 13, HbA1c <7.0% was achieved by 55.2% (Q2W) and 65.5% (QW); ≤6.5% by 37.9% and 24.1%. Gastrointestinal adverse events predominated and were mostly mild to moderate; no hypoglycaemia or cardiovascular events occurred.
CONCLUSIONS: Over 12 weeks, efsubaglutide alfa 3 mg Q2W provided glycaemic and CGM benefits comparable to 1 mg QW with favourable tolerability. These findings support the feasibility of a biweekly regimen as an alternative to weekly dosing; larger, longer-duration confirmatory trials in more diverse populations are warranted.
