Welcome to today’s edition of The Daily Bolus! The incretin landscape is rapidly evolving into the era of the “triple agonist,” with Eli Lilly and Novo Nordisk going head-to-head to push weight loss and A1C reduction to new extremes. Meanwhile, groundbreaking real-world data is showing that these blockbuster therapies are quietly transforming long-term care for the Type 1 diabetes community as well.
Lilly’s Retatrutide Flexes Major Muscle in Phase 3
Eli Lilly announced positive Phase 3 results for retatrutide, its investigational once-weekly triple hormone receptor agonist, in adults with type 2 diabetes. Over a 40-week trial period, patients on the highest 12 mg dose achieved up to a 2.0% reduction in A1C and lost a staggering average of 16.8% of their body weight, or 36.6 pounds.
Why It Matters: For individuals with type 2 diabetes, significant weight loss has notoriously been a difficult hurdle to clear alongside glycemic control. By targeting three separate receptors—GIP, GLP-1, and glucagon—retatrutide pushes the boundaries of metabolic management, offering unprecedented weight loss that impressively did not plateau during the trial.
Novo Nordisk Answers Back with UBT251 Phase 2 Success
Novo Nordisk and its partner, The United Laboratories, shared strong Phase 2 results from China for their own triple agonist candidate, UBT251. In a 24-week study of Chinese patients with type 2 diabetes, the drug achieved up to a 2.16% drop in HbA1c and a 9.8% reduction in body weight, effectively outperforming the 1 mg dose of Novo’s own blockbuster drug, semaglutide.
Why It Matters: This proves the “triple G” approach is the definitive next step beyond today’s highly successful single-agonist GLP-1 treatments like Ozempic. However, with Eli Lilly already wrapping up Phase 3 trials for its rival drug, industry analysts note that Novo Nordisk is currently lagging in the development race. Novo is planning global Phase 2 trials for late 2026, meaning UBT251 could reach the market years after retatrutide, potentially limiting its commercial impact.
GLP-1s Show Real-World Promise for Type 1 Diabetes
A large retrospective analysis from the Cleveland Clinic revealed that using GLP-1 receptor agonists in patients with Type 1 diabetes is associated with lower all-cause mortality and fewer hospital and emergency department visits over a two-year period. Crucially, researchers noted that these therapies did not increase the risk of dangerous diabetes-related complications like diabetic ketoacidosis (DKA) or severe hypoglycemia.
Why It Matters: While GLP-1s are currently only FDA-approved for Type 2 diabetes and obesity, they are increasingly being prescribed off-label for T1D patients who also battle insulin resistance, metabolic syndrome, or obesity. These findings validate that clinical trend, suggesting that adding a GLP-1 to an insulin regimen can safely reduce healthcare utilization and improve long-term outcomes for carefully selected patients with Type 1 diabetes.
The Diabettech Take
The era of the single-receptor incretin agonist is officially on notice. The data we are seeing from “triple G” (GLP-1/GIP/glucagon) agonists—both retatrutide and UBT251—are spectacular, promising massive weight loss alongside exceptional A1C normalization. However, the commercial reality is a race against the clock where Eli Lilly currently holds a clear and commanding head start over Novo Nordisk.
Beyond the corporate heavyweight battle, the Cleveland Clinic data on Type 1 diabetes is perhaps the most paradigm-shifting news of the day. It proves that the future of diabetes care, across both Type 1 and Type 2, is rapidly shifting toward treating the holistic metabolic profile—obesity, insulin resistance, and cardiovascular risk—rather than just chasing glucose numbers.
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I do not understand why this would shock or surprise anyone. I’ve known many T1D who’ve been using GLP1 off label with excellent results.
It seems to be surprising some healthcare professionals though…
you are not mentioning the risk of the G3. It contained glucagon agonist, which means it increased glucagon.This is the component that basically oxidizes fat I believe. For people who are not making insulin this could be a big risk. I appreciate that the theory that it will work in synergy with the GIP and GLP-1 to not cause a spike in blood sugar could be too… but then the person needs to figure out how the delayed gastric emptying, with increased insulin sensitivity and than add on glucagon will affect their blood sugar. It can get very complicated. I am not saying this is not a wonder drug an could be fantastic… but I am hoping that there will be studies on these drugs with T1Ds that are monitored to assist with understanding if this drug is also a miracle for T1Ds…. however this is only my take on it.
The studies are looking at T2D, which is all that this article is reporting on. Whether they work well in T1D remains to be seen, but there’s a long while to go before they’re available and able to be tested in that scenario.
A close friend w t1d tried GLP1 in a study years ago and had to drop out due to the protocol prescribed amount but more recently is giving it another shot and happy with results.