Endocrinology

Tirzepatide Improves Composite Metabolic Target Attainment Versus Semaglutide in Type 2 Diabetes

In SURPASS-2, tirzepatide increased attainment of standard and intensive HbA1c, blood pressure, LDL, and weight targets versus semaglutide 1 mg at 40 weeks. Three or more standard targets were achieved in 34% on semaglutide versus 42%, 53%, and 57% on tirzepatide 5, 10, and 15 mg. For intensive targets, three or more were achieved in 8% on semaglutide versus 15%, 20%, and 29% on tirzepatide across doses. Tirzepatide increased odds of HbA1c <7% (OR 1.50) and <6.5% (OR 1.88) and >10% and >15% weight loss versus semaglutide. 1

Complex Insulin Regimens Provide Small HbA1c Gains Over Basal With More Weight and Hypoglycemia

This network meta-analysis of 58 RCTs (19,122 adults) compared basal, basal-bolus, biphasic, and prandial regimens for type 2 diabetes. Compared with basal insulin, HbA1c reduction was only 0.31% greater with basal-bolus, 0.24% with biphasic, and 0.38% with prandial regimens. All complex regimens increased the chance of reaching HbA1c targets by about 30% but caused roughly 1 kg more weight gain. Severe hypoglycemia risk was borderline higher and insulin doses slightly greater with basal-bolus and biphasic regimens. 2

Semaglutide Enables Major Bolus-Focused Insulin Reductions in Type 1 Diabetes With Obesity

In ADJUST-T1D, adults with type 1 diabetes, obesity, and automated delivery on semaglutide 1 mg had a 22.6% reduction in total daily insulin at 26 weeks. Bolus insulin decreased 30.5%, exceeding the 15.6% decline in basal insulin, increasing the basal-to-total dose ratio from 0.56 to 0.62. Insulin units per kilogram fell from 0.72 to 0.60, indicating substantially lower insulin requirements with semaglutide. Early insulin reductions were mainly a direct drug effect, with weight loss and direct effects contributing similarly by week 26. 3

ICI-Induced Diabetes Is Uncommon but Frequently Requires Hospitalization and Intensive Care

Across 13,966 patients in 158 NCI trials including PD-1 or PD-L1 agents, immune checkpoint inhibitor–induced diabetes occurred in 0.52 per 100 treated patients. Incidence was higher with combination immunotherapy versus monotherapy (0.94% vs 0.37%; OR 2.68) and lower with concurrent chemotherapy (0.26% vs 0.65%; OR 0.38). Despite low incidence, 90% of affected patients required hospitalization at diagnosis and 43% needed intensive care. Marked hyperglycemia helped distinguish ICI-induced diabetes from other causes of treatment-related hyperglycemia. 4