Endocrinology

Canagliflozin benefits persist after eGFR declines below 20 mL/min/1.73 m² in diabetic CKD

In this post hoc CREDENCE analysis, 10% of participants’ eGFR declined below 20 mL/min/1.73 m² during follow-up. These patients had markedly higher absolute risk of kidney–cardiovascular events than those remaining above this threshold. Canagliflozin reduced the primary composite outcome similarly whether eGFR fell below 20 or not (HR 0.87 vs 0.69; no significant interaction). Adverse event rates were higher in those with very low eGFR but were similar between canagliflozin and placebo within this subgroup. Findings support continuing SGLT2 inhibition in T2D CKD until dialysis or transplantation, rather than stopping solely for eGFR <20. 1

GLP-1 RA weight-loss efficacy shows sex differences but little heterogeneity by age, BMI, or HbA1c

This systematic review and meta-analysis included 64 GLP-1 RA randomized trials evaluating weight loss by patient subgroups. Across six trials with nearly 20,000 patients, women lost more weight than men on GLP-1 RAs (10.9% vs 6.8% relative loss). No significant heterogeneity of treatment effect was seen by age, baseline BMI, race, ethnicity, or baseline HbA1c. These data suggest GLP-1 RAs provide broadly consistent weight-loss benefit across clinical strata, with greater average response in women. Clinicians can emphasize expected benefit across diverse patients while noting possible sex-based differences in magnitude of weight loss. 2

Tight, early glycemic control in GDM normalizes offspring obesity risk by age 10

This large Kaiser Permanente cohort followed over 200,000 pregnancies and offspring BMI from ages 2 to 10 years. Among 14,870 GDM pregnancies, four maternal glycemic management trajectories were defined from diagnosis to delivery. Children of mothers with stably optimal control had BMI and obesity risk similar to offspring unexposed to GDM by age 10. Progressively worse glycemic trajectories were associated with stepwise increases in childhood BMI and obesity risk, showing a dose–response pattern. Associations persisted, though attenuated, after adjusting for prepregnancy BMI, highlighting independent intrauterine glycemic effects. 3

Tirzepatide vs dulaglutide or semaglutide for MACE in T2D with ASCVD: two target-trial emulations

Commercial claims data were used to emulate two target trials in adults with T2D and established ASCVD initiating injectable incretins. After propensity matching, 9,233 tirzepatide–dulaglutide pairs and 25,266 tirzepatide–semaglutide pairs were analyzed. Tirzepatide users had fewer modified MACE events than dulaglutide users (IR 31.3 vs 39.4 per 1,000 person-years; HR 0.80). This benefit appeared driven by lower all-cause mortality with tirzepatide versus dulaglutide (HR 0.60). Modified MACE rates were similar for tirzepatide and semaglutide (HR 1.03), suggesting comparable cardiovascular protection in routine care. 4