Endocrinology

Mazdutide produces large A1c and weight reductions in early Chinese T2D

In Chinese adults with early T2D on lifestyle alone, weekly mazdutide 4 or 6 mg markedly improved glycemia versus placebo at 24 weeks. HbA1c fell by 1.6–2.2 percentage points with mazdutide versus 0.1 with placebo, with many more patients achieving HbA1c <7%. Weight decreased 5.6–7.8% on mazdutide versus 1.3% with placebo, and more patients met ≥5% weight-loss and composite A1c–weight targets. Adverse events were mainly gastrointestinal, similar to GLP-1 RAs, supporting a familiar and generally acceptable safety profile. 1

1-hour OGTT glucose clearly outperforms fasting and 2-hour measures for T2D diagnosis

Across five cohorts totaling 11,968 adults, 1-hour plasma glucose provided superior diagnostic accuracy for T2D versus FPG, 2-hour PG, and HbA1c. Pooled AUC was 0.97 for 1-hour glucose versus 0.85 for FPG plus HbA1c, with consistently higher sensitivity and specificity in each cohort. Results support the IDF-recommended 1-hour glucose cut-off as a primary diagnostic threshold rather than relying on fasting or 2-hour values. Clinically, adding or prioritizing 1-hour glucose during OGTT may better detect early diabetes in high-risk individuals. 2

Stopping GLP-1 RAs causes substantial weight and A1c rebound in obesity and T2D

This meta-analysis of 18 RCTs (3,771 participants) quantified metabolic rebound after GLP-1 RA discontinuation in obesity and diabetes. In obesity trials, GLP-1 RA cessation led to 5.6 kg weight regain, A1c increase, and worsening waist, BMI, systolic blood pressure, and fasting glucose. In T2D, discontinuation caused 2.0 kg weight regain and 0.65% HbA1c rise, despite stable fasting glucose. Longer follow-up and semaglutide use were associated with larger weight and blood pressure rebound than liraglutide. These findings reinforce treating GLP-1 RAs as chronic therapy and planning structured exit or transition strategies. 3

Fully closed-loop insulin improves T1D glycemia without meal boluses

In a randomized crossover trial of 34 adolescents and adults with T1D, a fully closed-loop system was compared with usual care hybrid closed loop. During home use, mean sensor glucose decreased from 178 to 164 mg/dL with fully closed loop, despite no mealtime boluses. Time in range (70–180 mg/dL) and 70–140 mg/dL improved, mainly overnight, with reductions in time >180 and >250 mg/dL. Time <70 and <54 mg/dL was noninferior to usual care, indicating no excess hypoglycemia risk. These data support fully automated insulin delivery as a safe option to simplify care, particularly for patients struggling with bolus adherence. 4