ADA 2026 closes with retatrutide, orforglipron and CagriSema data

The American Diabetes Association's 86th Scientific Sessions ran June 5 to 8, 2026, in New Orleans, where investigators presented phase 3 results for the experimental drugs retatrutide, orforglipron, CagriSema and survodutide. The meeting also introduced the 2026 ADA Standards of Care, which raise cardiovascular and kidney risk reduction to a co-primary treatment goal alongside blood sugar control ^[1].

Retatrutide posts the largest weight numbers

Eli Lilly's retatrutide, an investigational once-weekly injection that activates GLP-1, GIP and glucagon receptors, produced average weight loss of 28.3% at 80 weeks in TRIUMPH-1, a trial of 2,339 adults with obesity but not diabetes. In that study, 45.3% of participants on the highest dose lost at least 30% of their body weight ^[1]. Another account of the same trial describes the 80-week result differently, reporting roughly 20% weight loss among participants who stayed on the drug, with the highest dose exceeding 30% in an extension out to 104 weeks ^[2]. Retatrutide is not FDA approved. Lilly is expected to file a new drug application in 2026, with approval most likely in 2027 or 2028 ^[1].

In the companion TRANSCEND-T2D-1 trial, adults with type 2 diabetes lowered A1C by up to 2.0% and lost up to 36.6 pounds over 40 weeks, with up to 46% reaching a normal A1C. Triglycerides fell by up to 39.6%, non-HDL cholesterol by up to 19.8%, and systolic blood pressure by 6.4 millimeters of mercury ^[1]. TRIUMPH-1 also reported a 73.1% reduction in knee pain scores and a 60.6% reduction in sleep apnea events ^[1]. Urinary tract infections appeared in 7.5% to 8.8% of retatrutide participants versus 5.3% on placebo, a signal investigators flagged for further evaluation ^[1]. Dr. Lee Kaplan warned at the meeting about the dangers of people obtaining what is claimed to be retatrutide from compounded and illicit sources ^[2].

Oral and combination drugs

Orforglipron, sold as Foundayo, cut A1C by 1.54% to 2.05% across three doses when added to insulin glargine in the ACHIEVE-5 trial, compared with 0.77% for placebo, in adults with a mean diabetes duration of 15 years. Weight fell 2.7% to 6.1% on the drug while the placebo group gained an average of 0.6% ^[1]. The earlier ACHIEVE-3 trial found orforglipron superior to oral semaglutide on A1C and produced 73.6% more relative weight loss at 52 weeks ^[1]. Orforglipron has not completed a cardiovascular outcomes trial, while oral semaglutide showed cardiovascular benefit in the SOUL trial ^[1]. It has cost $149 per month for self-pay patients since its April 2026 launch ^[1].

CagriSema, Novo Nordisk's fixed-dose combination of the amylin analog cagrilintide and semaglutide, produced the first phase 3 diabetes data for the pairing. The three REIMAGINE trials met their primary A1C endpoints and confirmed weight-loss secondary endpoints, with simultaneous publication in The Lancet Diabetes & Endocrinology and The Lancet ^[1]. Novo Nordisk has filed CagriSema with the FDA for a weight-loss indication and targets a US launch in early 2027 ^[1]. A February 2026 head-to-head comparison found Zepbound, or tirzepatide, produced 25.5% average weight loss versus CagriSema's 23% at 84 weeks ^[1].

Survodutide, a glucagon/GLP-1 dual agonist from Boehringer Ingelheim and Zealand Pharma, achieved 16.6% placebo-adjusted weight reduction at 76 weeks in SYNCHRONIZE-1 ^[1]. In a companion trial in metabolic dysfunction-associated steatotic liver disease, 84% of participants on survodutide had at least a 30% reduction in liver fat versus 24% on placebo, alongside 12% weight loss ^[2]. Discontinuation because of gastrointestinal side effects was relatively high ^[2].

Two oral small molecules reported phase 2 results. AstraZeneca's elecoglipron lowered A1C by 1.9% at the highest dose in the SOLSTICE trial, compared with 1.3% for a 14 milligram oral semaglutide arm, and produced 10.5% weight loss over 36 weeks in the VISTA trial, where about a third of patients at the highest dose discontinued ^[2]. Structure Therapeutics' aleniglipron produced 11.3% weight loss over 38 weeks, and 16% over 56 weeks in an open-label extension ^[2].

Outside the GLP-1 class, a prespecified analysis of the VESALIUS-CV trial tested the PCSK9 inhibitor evolocumab in people with high-risk type 2 diabetes and no prior heart attack or stroke. Evolocumab reduced LDL cholesterol by more than 50%, to an average of 45 milligrams per deciliter. Over a median 4.6 years, that subgroup showed a 29% reduction in three-point major adverse cardiovascular events and a 21% reduction in four-point events ^[1].

Why it matters for patients

With heart and kidney risk reduction now listed as a co-primary goal in the 2026 ADA Standards of Care, the measures that matter in a clinic visit may extend beyond A1C ^[1]. For people already taking a GLP-1, the meeting showed a pipeline aimed at the same conditions from different mechanisms: glucagon, amylin and triple-hormone combinations, plus oral options ^[1][2].

Retatrutide is still investigational, and no regulator has approved it, which is why clinicians at the meeting raised concerns about compounded and illicit versions sold as retatrutide ^[2]. Orforglipron offers an oral option with no fasting requirement and a $149 monthly self-pay price, but it lacks the cardiovascular outcomes data that oral semaglutide has ^[1]. If approved, CagriSema would be the first product on the US market combining amylin and GLP-1 pathways, and Novo Nordisk says it would carry the strongest weight-loss label available at its expected launch ^[1].

What happens next

Lilly is expected to file retatrutide for FDA review in 2026, with approval most likely in 2027 or 2028 ^[1]. CagriSema has already been filed for a weight-loss indication, with a US launch targeted for early 2027 ^[1]. The urinary tract infection signal seen with retatrutide has been flagged for further evaluation before regulatory submission ^[1].