Research · Evidence roundup

ADA 2026: the next wave of diabetes and obesity drugs, explained

By Erik Jones · Jun 20, 2026 · 9 min read

The headliner: retatrutide, a triple agonist

The most talked-about agent at the meeting was retatrutide, an injection that activates three hormone receptors at once — GLP-1, GIP, and glucagon. Most current drugs hit one or two; retatrutide hits all three, which is why the field has watched it so closely.

Two phase 3 studies were presented. In TRANSCEND-T2D-1, adults with fairly early type 2 diabetes (about 2.5 years since diagnosis on average) who were not taking diabetes medicine and were above target despite diet and exercise took retatrutide for 40 weeks. According to the data presented, they saw up to a 2% reduction in A1c and a 16.8% reduction in body weight — an average of about 36.6 pounds — along with improvements in non-HDL cholesterol, triglycerides, and blood pressure. Most side effects were the stomach-related kind seen with other GLP-1 drugs; a small share of people also reported unusual skin sensations.

The obesity trial, TRIUMPH-1, was the eye-opener. It enrolled adults with obesity (or overweight plus a weight-related health problem) who did not have diabetes, starting at an average body mass index of about 40. Over 80 weeks, those on the highest dose (12 mg) lost an average of 70.3 pounds, or 28.3% of their body weight, and 45% lost at least 30%. In a JAMA interview, the ADA’s Dr. Rita Kalyani described that as on par with metabolic or bariatric surgery. People who stayed on the drug in a study extension kept losing weight out to 104 weeks (two years). Retatrutide is still investigational — not approved — but these are among the largest weight-loss figures reported for a drug to date.

Adding amylin to the mix: CagriSema

A second approach combines two injectable hormones in one shot: semaglutide (a GLP-1 drug) and cagrilintide, an analogue of amylin. Amylin is a hormone released by the same pancreatic beta cells that make insulin, and it helps control blood sugar after meals — one amylin drug, pramlintide, is already approved for use alongside insulin. CagriSema pairs that mechanism with GLP-1.

The REIMAGINE trials tested it. REIMAGINE 1, a phase 3 study in 189 people with type 2 diabetes, gave CagriSema as a once-weekly injection, followed by 12 weeks off treatment, designed to see whether the benefit lasts after stopping; it lowered blood sugar. REIMAGINE 3 looked at people already on basal insulin and found that, on the higher dose, A1c fell on average from 8.8% to about 6.5%, with weight loss of about 12% and — notably for insulin users — no severe low-blood-sugar events. Like retatrutide, CagriSema is investigational.

A first for type 1 diabetes: acmopatide

Almost all incretin research has been in type 2 diabetes and obesity; there are no incretin-based drugs approved for type 1 diabetes. That’s what made acmopatide notable. It is a once-daily dual GLP-1/GIP agonist, and a phase 2 trial tested it in 111 adults with type 1 diabetes who also had overweight or obesity (mean age 41).

The drug improved blood glucose and produced dose-dependent weight loss of up to about 7%, and reduced participants’ insulin use by up to 15% versus placebo. The trial did not report whether this changed low-blood-sugar risk, which is a key question for type 1 diabetes. It was generally well tolerated. This is early, phase 2 work and still investigational, but it’s a real signal that incretin therapies could eventually reach type 1 diabetes.

Beyond drugs: CGM for type 2 not on insulin

Not everything at the meeting was a drug. The CONNECT trial asked whether continuous glucose monitors — devices most often prescribed for people on insulin — help people with type 2 diabetes who are not on insulin. It was a randomized controlled trial across 22 US primary care practices in 283 adults, with A1c ranging widely from 7.1% to 14.9%, over 26 weeks. Many were already on other treatments (37% on an SGLT2 inhibitor, 40% on an incretin drug), so the question was whether a CGM adds anything on top.

It did. Over 26 weeks, A1c fell by 1.6 points with a CGM and by 0.7 points with usual care, a difference of 0.9 points. People using a CGM also spent about five more hours a day in the target glucose range, with no severe lows in either group. 82% of the CGM group lowered their A1c by at least half a point, compared with 56% on usual care. The full results have since been published in the New England Journal of Medicine; see our full breakdown of the CONNECT trial. Because CGMs aren’t always covered for people who don’t use insulin, the trial carries real policy and coverage implications — and unlike the drugs above, CGMs are already on the market, though coverage for people not on insulin varies.

Where mazdutide and orforglipron fit

Two other agents discussed at the meeting are ones we’ve covered in depth. Mazdutide, a GLP-1/glucagon dual agonist approved in China, posted a placebo-subtracted weight loss of about 15% in the 60-week GLORY-2 trial — see our full breakdown of GLORY-2. And orforglipron, a small-molecule GLP-1 taken as a daily pill (with no food or water restrictions), was FDA-approved for weight management this spring and lowered A1c by up to about 1.9 points when added to insulin in type 2 diabetes — see what the orforglipron trial showed. For how those two fit together, we pulled them into a separate roundup.

Step back from any single number and the pattern is clear: diabetes and obesity medicine is moving from one-hormone drugs to two- and three-hormone combinations, from injections toward pills, from type 2 toward type 1, and from drugs alone toward tools like CGMs. Retatrutide’s weight-loss figures approaching surgical territory are the headline, but the broader story is breadth — more mechanisms aimed at more people.

The cautions are the familiar ones. Almost everything here is investigational, the headline numbers often come from the most favorable analysis, and the questions that decide real-world value — long-term safety, durability after stopping, cardiovascular benefit, and above all cost and access — are exactly the ones a single meeting can’t answer. For people on the obesity–diabetes continuum, ADA 2026 is a reason for grounded optimism about the pipeline, not a prompt to act today.

Not medical advice. Educational summary of published research. Last reviewed Oct 27, 2026.