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Jump to Key Points MILAN — Tirzepatide (Mounjaro, Eli Lilly) improved markers of beta-cell function and insulin sensitivity in people with recent-onset type 2 diabetes (T2D), a new prespecified analysis of SURPASS-EARLY showed.
These findings could explain the superior glycemic control seen with tirzepatide compared with intensified conventional care (ICC) seen during the first 2 years of the trial, said Steven Kahn, MB ChB, professor of medicine and director of the University of Washington Diabetes Research Center and the VA Puget Sound Health Care System, Seattle, who presented the results here at the European Association for the Study of Diabetes (EASD) 2026 Annual Meeting.
"I think [this] analysis looking at beta-cell function and insulin sensitivity clearly shows that both of them are important in determining this outcome," Kahn told Medscape Medical News.
Initial Results From SURPASS-EARLY
The study included a total of 794 individuals with T2D of a duration of 4 years or fewer who were inadequately treated with metformin (A1c, 7.1-9.5; overall mean at baseline, 7.81%). Study participants were randomized either to tirzepatide — 15 mg or maximal tolerated dose — or to ICC, which included a variety of approved medications for treating T2D along with metformin, including oral or injectable GLP-1 agonists, SGLT2 inhibitors, or DPP-4 inhibitors, but not tirzepatide or insulin. Drug additions and changes were permitted within labeling, but the majority (88%) took just one in addition to metformin.
- Tirzepatide improved β-cell function markers in recent-onset T2D.
- Oral glucose insulin sensitivity also ↑ vs intensified conventional care.
- At 104 weeks, A1c 5.56% vs 6.3%; weight loss 15.8 kg vs 6.5 kg.
- Normoglycemia achieved in 69.9% vs 28.1%; A1c ≤6.5% in 91% vs 65.5%.
- Mechanism may involve weight loss + direct metabolic effects; mediation unclear.
As previously reported by Medscape Medical News, at 104 weeks, A1c in the tirzepatide group was reduced to a mean of 5.56%, compared to a mean of 6.3% in the ICC group, a significant difference (P < .001, for the efficacy estimand). Body weight was reduced from a mean baseline of 100.1kg by 15.8kg with tirzepatide vs only 6.5 kg with ICC (P < .001).
The proportion of patients achieving A1c levels of 6.5 or below at year 2 were 91% with
tirzepatide vs 65.5% with ICC. Those achieving A1c below 5.7 — ie, normoglycemia — were 69.9% vs 28.1%, respectively.
Beta-Cell Function, Insulin Sensitivity
The current analysis looked at oral glucose tolerance test-based markers of beta-cell function and insulin sensitivity at 2 years.
The following changes all showed superiority of tirzepatide:
- Insulinogenic index, a measure of early-phase beta-cell insulin secretion and beta-cell function in response to a glucose load (change from baseline 7.96 pmol/mmol vs 4.58 pmol/mmol; P = .042)
- Beta-cell glucose sensitivity, the ability of the beta cells to adjust their insulin secretion based on detected blood glucose level changes (55.1 vs 36.0 pmol/min/m2/mM; P < .001)
- Insulin secretion rate at 9.2 mM/l glucose (168.72 vs 131.24 pmol/min; P = .44)
- Oral glucose insulin sensitivity, an estimate of whole-body insulin sensitivity and glucose clearance (95.5 vs 58.98 mL/min-1/m-2; P < .001)
The results "suggest that tirzepatide may have an increased ability to achieve and sustain normoglycemia for two years," Kahn said in his presentation. He added that clinicians should start considering initiation of tirzepatide early in the course of T2D, and that this line of treatment could be addressed in the guidelines.
Kahn told Medscape that the effect of tirzepatide at maximally tolerated dose compared to ICC might have been even better had there been a standardized approach to the ICC, which was practitioner-based.
In addition, "we don't know how much of the impact tirzepatide had on glycemia and on beta cell function and insulin sensitivity measures is actually mediated by weight loss vs other things, and so that's got to be sorted out," he said. "The plan is to do those analyses before we submit the final paper."
Recent-Onset Population
Asked to comment, session moderator Dario Tuccinardi, MD, assistant professor of endocrinology and senior researcher at the Campus Bio-Medico University of Rome, pointed out that — because this was a recent-onset T2D population — the beta cells would be expected to have a better response than if the drug were initiated later in the course of the condition. These patients "could be healthier compared to [those with] long-standing diabetes," he told Medscape Medical News.
Moreover, "this medication acts on insulin secretion, so it controls the glucose toxicity and the lipotoxicity," and this is probably the main reason "why you have this improvement in these surrogates of beta cell function," along with weight loss.
Tuccinardi concluded that more specific studies that don't use surrogate markers are needed, although he acknowledged this was difficult, adding that "eventually, we will have to look into the mechanistic data."
Kahn reported disclosures with AltPep, Amgen, Biomea Fusion, Congruence Therapeutics, Corcept Therapeutics, Eli Lilly, General Medicines, Hoffman La-Roche, Kayothera, Merck, Neurimmune, and Novo Nordisk.
Tuccinardi has received funding for providing educational sessions from Novo Nordisk, AstraZeneca, Eli Lilly, Mundipharma, and Boehringer Ingelheim; institutional research grant support or funding for clinical trials from Novo Nordisk, Abbott, Amgen, LJ Pharma, Eisai, Eli Lilly, AstraZeneca, and Boehringer Ingelheim; and institutional scientific board and/or consulting from Novo Nordisk.
Miriam E. Tucker is a freelance journalist based in the Washington DC area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR's Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social
