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ADA 2026 obesity studies

CE / CME

Translating Emerging Obesity Evidence Into Clinical Action: Highlights From ADA 2026

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Pharmacists: 1.00 contact hour (0.1 CEUs)

ABIM MOC: maximum of 1.00 Medical Knowledge MOC point

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Nurse Practitioners/Nurses: 1.00 Nursing contact hour

Released: July 21, 2026

Expiration: July 20, 2027

Donna H. Ryan
Donna H. Ryan, MD
CME/CE Information

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TRIUMPH-1: Why It Matters

The first study I will discuss is TRIUMPH-1, a phase III trial evaluating retatrutide vs placebo in adults with overweight or obesity.

Retatrutide is a once-weekly injectable triple agonist that targets the GIP, GLP-1, and glucagon receptors.5 TRIUMPH-1 attracted considerable interest because of the expectation that this triple agonism would produce greater weight loss than previously reported. From a clinical perspective, TRIUMPH-1 did just that—positioning GIP/GLP-1/glucagon agonism as a potential new frontier in obesity management, pending its FDA approval and other important factors.1

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TRIUMPH-1: Study Design

Going into more detail, TRIUMPH-1 (NCT05929066) was a multicenter, double-blind, placebo-controlled, randomized phase III trial that enrolled more than 2300 adults with obesity or overweight and at least 1 weight-related comorbidity. Those with diabetes, prior or planned metabolic surgery, weight change of more than 5 kg, or use of over-the-counter weight loss agents within the prior 90 days were excluded.

Enrolled patients were randomized to receive retatrutide 4 mg, 9 mg, or 12 mg or placebo via once-weekly SC injection. The first 500 patients who reached their target dose at 80 weeks were then eligible to continue retatrutide at the maximum tolerated dose for an additional 24 weeks in the extension study.

TRIUMPH-1 also included dedicated cohorts for patients with OSA and knee osteoarthritis (OA). The primary endpoint was change in total body weight with retatrutide 9 mg and 12 mg at 80 weeks. Key secondary endpoints included change in total body weight with retatrutide 4 mg and cardiometabolic outcomes, achievement of clinically relevant weight-loss thresholds, and safety at 80 weeks.1

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TRIUMPH-1: Baseline Characteristics and Anthropometric Measures

As mentioned, it is helpful to understand the patient population that was studied, including their baseline characteristics, when evaluating new evidence. In TRIUMPH-1, enrolled patients were representative of the population commonly seen in obesity clinical trials. Approximately 65% were female, and the mean age was approximately 49 years. Those in the knee OA cohort were somewhat older, with a mean age of 56 years. Those in the OSA cohort were younger, with a mean age of 48 years.

The mean BMI across all patients was approximately 40 kg/m²—reflecting a population with predominantly class III obesity. Baseline anthropometric characteristics like mean body weight, waist circumference, and waist-to-height ratio were well balanced across all study arms, indicating successful randomization. The study also included patients from diverse racial and ethnic backgrounds.1

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TRIUMPH-1: Mean Change in Total Body Weight at 80 Weeks

The efficacy results demonstrated substantial, dose-dependent reductions in total body weight. Looking at the efficacy estimand, mean weight loss at 80 weeks was -19.0% with retatrutide 4 mg, -25.9% with retatrutide 9 mg, and -28.3% with retatrutide 12 mg vs -2.2% with placebo (P <.001 for all comparisons).

According to the treatment regimen estimand (or the observed treatment effects), there were somewhat smaller but still substantial reductions in total body weight: -17.6%, -23.7%, and -25.0% with retatrutide 4 mg, 9 mg, and 12 mg, respectively, vs -3.9% with placebo (P <.001 for all comparisons).1

These findings are the largest mean weight reductions reported to date with obesity management medications (OMMs) and support the potential contribution of triple agonism targeting the GIP, GLP-1, and glucagon receptors.

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TRIUMPH-1: Key Secondary Outcomes at 80 Weeks

Key secondary outcomes further demonstrated the magnitude of response observed with retatrutide vs placebo. At 80 weeks, 65.3% of patients treated with retatrutide 12 mg achieved a BMI <30 kg/m², compared with 60.2% treated with retatrutide 9 mg, 40.3% treated with retatrutide 4 mg, and 7.6% treated with placebo. Furthermore, 33.3% of patients in the retatrutide 12 mg arm achieved a BMI <25 kg/m².

Across clinically relevant weight-loss thresholds, retatrutide responses were consistently robust. In the 12 mg arm, 97.3% of patients achieved at least 5% weight loss, 93.2% achieved at least 10% weight loss, 87.5% achieved at least 15% weight loss, 76.2% achieved at least 20% weight loss, 62.5% achieved at least 25% weight loss, 45.3% achieved at least 30% weight loss, and 27.2% achieved at least 35% weight loss.1

These results demonstrate clinically meaningful weight loss across a broad range of response thresholds and improvements in select cardiovascular risk factors with retatrutide.

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TRIUMPH-1 Extension: Mean Change in Total Body Weight at 104 Weeks

The TRIUMPH-1 extension study further reported significant and maintained weight loss at 104 weeks among enrolled patients. According to the efficacy estimand, the mean change in total body weight was -25.7%, -28.7%, and -29.9% in the retatrutide 4 mg, 9 mg, and 12 mg arms, respectively, compared with -18.9% in the placebo arm (P <.001 for all comparisons).1

These long-term outcomes demonstrate patients’ ability to sustain their clinically meaningful weight loss over 2 years with continued treatment.

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TRIUMPH-1: Safety

The safety profile of retatrutide matches the expected balance between efficacy and tolerability. Adverse events (AEs) and serious AEs occurred more frequently with retatrutide than with placebo. That is, 7.7% of patients in the retatrutide 4 mg and 9 mg arms experienced serious AEs, compared with 10.5% of those in the retatrutide 12 mg arm and 5.5% of those in the placebo arm.

Gastrointestinal AEs were more common and led to treatment discontinuation in 2.2% to 4.6% of patients across all retatrutide arms vs 1.2% of those in the placebo arm. Nausea, diarrhea, constipation, and vomiting incidence increased with higher retatrutide doses and are consistent with the known gastrointestinal-related effects of incretin-based therapies. Although gastrointestinal-related AEs were more common with increasing retatrutide doses, relatively few participants discontinued treatment because of these events.

At the time of the ADA 2026 presentation, additional details regarding serious AEs in TRIUMPH-1 were not available.1 Further analyses will help clarify the nature of these AEs and determine whether they were related to the magnitude or rate of weight loss with retatrutide use.

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TRIUMPH-1: Clinical Interpretation

Retatrutide is expected to undergo regulatory review, and additional information regarding its approval status, labeling, and long-term use should become available over time.

The magnitude of weight loss observed in the phase III TRIUMPH-1 trial has the potential to reshape treatment expectations for OMMs, particularly among patients with class III obesity. These findings also suggest that obesity management goals may extend beyond total body weight reductions to include clinically meaningful anthropometric targets, such as achieving a BMI <30 kg/m² or, for some patients, below 25 kg/m².

The dedicated OSA and knee OA cohorts in TRIUMPH-1 may provide additional insights into the effects of OMM use on obesity-related comorbidities, as these data become available. Additional evidence regarding long-term safety, durability, and management beyond 2 years with retatrutide will also be important.

Regardless, these findings are encouraging and support triple agonism as a potentially important future option for obesity management.1

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