Ann Intern Med
Tirzepatide outperforms standard care in early diabetes
Clinical takeaway: In patients with recently diagnosed T2D whose blood sugar isn't controlled on metformin, early tirzepatide produces substantially better glycemic and weight outcomes than standard care.
Establishing improved glycemic control after a type 2 diabetes (T2D) diagnosis is associated with lasting reductions in microvascular and cardiovascular complications. But conventional stepwise treatment, starting with metformin and then additional agents as needed, often fails to maintain target HbA1c over time. The SURPASS-EARLY trial tested whether starting tirzepatide soon after metformin failure could achieve more durable control than standard escalation.
Among 794 adults with T2D diagnosed within the past four years and inadequate control on metformin, 60% of patients on tirzepatide reached normoglycemia (HbA1c below 5.7%) at two years, compared with 24% on standard care. Mean HbA1c dropped 1.99 percentage points on tirzepatide versus 1.32 on standard care, a treatment difference of 0.68 percentage points. Weight loss averaged 13.8 kg (30.4 lbs) on tirzepatide versus 5.9 kg (13.0 lbs) on standard care, and waist circumference dropped 11.6 cm versus 5.4 cm. 44% of patients on tirzepatide lost at least 15% of body weight, compared with 12% on standard care.
The open-label, phase 4 trial enrolled patients with baseline HbA1c between 7.0% and 9.5% across 78 sites in 10 countries. This is the two-year interim report from a planned four-year trial.
The standard care arm was not a placebo or basic care: 85% of those patients were taking a GLP-1 receptor agonist at week 104, mostly injectable semaglutide. Tirzepatide's advantage was therefore measured against aggressive contemporary treatment, not against undertreatment.
Gastrointestinal adverse events, mostly mild to moderate, were more common with tirzepatide (56% versus 38%), and 4.5% of tirzepatide patients discontinued treatment due to adverse events versus 0.3% on standard care. Hypoglycemia rates were low and similar in both groups. One case of pancreatitis was reported in the tirzepatide arm. The trial was funded by Eli Lilly, and 8 of 11 authors are company employees.
"These findings support the concept that early initiation of tirzepatide treatment could establish better and potentially more durable glycemic control than can be achieved with conventional care," the authors wrote.
Source: Del Prato S. Ann Intern Med. 2026 May 26. Tirzepatide versus intensified conventional care after 2 years of treatment in early type 2 diabetes: a randomized clinical trial