This is a special edition summarizing three studies from the recent American Diabetes Association Conference hosted in June 2025.
The headliner: Once-monthly GLP1-GIP medication leads to 15% weight loss.
Yes, you read that correctly; MariTide (Maridebart cafraglutide) is a once-monthly medication. Think of it as a long-acting version of tirzepatide. In this phase 2, double-blind, placebo-controlled, dose-ranging trial, patients randomized to MariTide lost between 12% to 16% of their body weight. The study included a sub-cohort of patients who also had T2DM, and Maritide led to a 1.2 to 1.6% drop in A1C, whereas the placebo group had a slight increase in their A1C. GI side effects were common with MariTide, especially in patients receiving higher doses of the medication.
The 2nd headliner: Meet the new oral GLP1 agonist (aka Orforglipron).
In this phase 3, double-blind, placebo-controlled trial, 559 patients were randomly assigned to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks. Patients were included if they had type 2 diabetes treated only with diet and exercise, a hemoglobin A1C between 7.0% and 9.5%, and a body-mass index of at least 23 kg/m². Patients randomized to orforglipron had a drop in their A1C of about 1.3% and drop in weight of about 6%, whereas the placebo group had a 0.4% drop in A1C and 2% drop in weight. Permanent discontinuation of orforglipron or placebo due to adverse events occurred in 6% of participants receiving orforglipron and 1% of participants receiving placebo.
Hidden gem: Can stem cell-derived islets treat type 1 diabetes?
The results of this (very) small single-arm phase 1-2 trial suggests the answer might be yes. The study included 14 patients who had type 1 diabetes and were dependent on insulin for at least 5 years. The intervention was an infusion of zimislecel (allogenic stem-cell derived islet-cell therapy) via the portal vein. Two patients died (unrelated to the treatment), and the remaining 12 patients achieved an A1C less than 7%. Ten of the 12 patients had insulin independence and were not using any exogenous insulin 1-year post stem cell infusion. A larger phase 3 trial is ongoing, and if it confirms the benefits observed in this small study, it will truly be a game changer.
The take home points:
[1] Once-monthly MariTide led to 12–16% weight loss and up to 1.6% A1C reduction.
[2] Orforglipron, an oral GLP1 analogue, decreased A1C by ~1.3% and weight by ~6% among adults with T2DM.
[3] Stem cell-derived islets (Zimislecel) restored insulin independence in 10 of 12 patients with type 1 diabetes.