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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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ATTAIN-1 Post Hoc Analysis: Why It Matters

The next study is the ATTAIN-1 post hoc analysis, which evaluated β-cell function and insulin sensitivity with orforglipron treatment according to patients’ baseline glycemic status. I think this is a particularly interesting analysis because OMMs may provide additional benefits that extend beyond weight loss alone.

Orforglipron is an oral nonpeptide GLP-1 RA taken once daily. Unlike peptide-based GLP-1 RAs, orforglipron is a small-molecule therapy that activates the GLP-1 receptor.6 In addition to promoting clinically meaningful weight loss, there is considerable interest in its potential cardiometabolic effects.

In this study, investigators assessed Matsuda Index, Homeostasis Model Assessment 2 for Insulin Resistance (HOMA2-IR), and Homeostasis Model Assessment 2 for β-cell Function (HOMA2-B) scores. Outcomes were compared between patients receiving orforglipron vs placebo with normoglycemia vs prediabetes.2

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ATTAIN-1: Study Design

ATTAIN-1 (NCT05869903) was a multinational, double-blind, placebo-controlled, randomized phase III trial that enrolled more than 3000 patients with obesity or overweight and at least 1 weight-related comorbidity who reported at least 1 previous unsuccessful dietary effort to lose weight. Key exclusion criteria included diabetes, prior or planned metabolic surgery, and a self-reported body weight change of more than 5 kg within the 90 days before screening.

Enrolled patients were randomized to receive oral orforglipron 6 mg, 12 mg, or 36 mg or placebo once daily. These orforglipron capsule doses correspond to FDA-approved, currently available bioequivalent tablet doses: 6 mg, 12 mg, and 36 mg capsules are equivalent to 5.5 mg, 9 mg, and 17.2 mg tablets, respectively.7

The primary endpoint was mean change in total body weight at 72 weeks. Key secondary endpoints included change in cardiometabolic outcomes and safety at 72 weeks. This post hoc analysis evaluated changes in β-cell function and insulin sensitivity by patients’ baseline prediabetes status.2

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ATTAIN-1 Post Hoc Analysis: Baseline Characteristics

Looking at the baseline characteristics among the prediabetes and normoglycemia cohorts, those with prediabetes were slightly older. The mean age was approximately 49 and 43 years for patients with prediabetes and normoglycemia, respectively. Mean body weight and BMI were generally similar between the 2 cohorts.

As expected, patients with prediabetes had higher means for fasting insulin, fasting glucose, and A1C. They also had lower Matsuda Index and higher HOMA2-IR scores, which are consistent with having greater insulin resistance. Baseline HOMA2-B scores differed between cohorts, as well, illustrating the differences in β-cell function associated with prediabetes.2

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ATTAIN-1: Mean Change in Body Weight at 72 Weeks

Mean weight loss reported at 72 weeks was -7.5%, -8.4%, and -11.2% with low-, intermediate-, and high-dose orforglipron, respectively, compared with -2.1% with placebo (P <.001 for all comparisons).8

One practical advantage of orforglipron is that it is administered without the fasting requirements associated with oral peptide-based GLP-1 RAs. Orforglipron should be taken once daily with or without food, and patients do not have to wait to eat, drink, or take other medications.6 This makes orforglipron relatively simple to incorporate into daily practice.

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ATTAIN-1 Post Hoc Analysis: Insulin Sensitivity and β-Cell Function at Wk 72

Going back to the post hoc analysis, orforglipron demonstrated improvements in insulin sensitivity and β-cell function regardless of patients’ baseline prediabetes status. These improvements were observed at 72 weeks in Matsuda Index, HOMA2-IR, and HOMA2-B scores.

These results suggest that orforglipron improves markers of insulin sensitivity and β-cell function in adults with overweight or obesity, with or without prediabetes. However, this analysis did not establish whether the metabolic effects were independent of weight loss. Because of the post hoc study design, this evidence should be interpreted as hypothesis generating only.2

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ATTAIN-1: Safety

The safety profile of orforglipron was consistent with what has been observed among other GLP-1 RAs. In ATTAIN-1, the most frequently reported AEs were nausea, diarrhea, constipation, vomiting, and dyspepsia, which were generally mild to moderate. No new safety findings emerged in this post hoc analysis.2

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ATTAIN-1 Post Hoc Analysis: Clinical Interpretation

I believe the ATTAIN-1 post hoc analysis is relevant, especially as oral GLP-1 RAs continue to expand OMM options for patients with obesity. Its results further support discussions about orforglipron use for weight loss as well as for improvements in insulin sensitivity and β-cell function, regardless of patients’ baseline prediabetes status.

Because this is a post hoc analysis, the evidence should not be interpreted as establishing causality. Nevertheless, these findings support the idea that oral GLP-1 RAs may offer metabolic benefits beyond weight loss alone.2

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