TOPLINE

Once-daily oral orforglipron led to clinically meaningful weight loss over 72 weeks in adults aged 65 years or older with overweight or obesity, regardless of type 2 diabetes (T2D) status, while maintaining a safety profile similar to that of other GLP-1s.

METHODOLOGY

• Orforglipron is a once-daily oral GLP-1 drug that has shown substantial weight loss benefits in obesity trials, but data on older patient populations remain limited.
• Using data from two phase 3 clinical trials, researchers conducted a post hoc analysis to evaluate the efficacy and safety of orforglipron as an adjunct to healthy diet and physical activity in adults aged 65 years or older with overweight or obesity, including those with T2D and those without T2D.
• The analysis included 616 older adults with overweight or obesity and a history of at least one unsuccessful dietary attempt to lose weight; 613 received tablet-equivalent doses of 5.5 mg (n = 118), 9 mg (n = 135), or 17.2 mg (n = 146) of orforglipron or placebo (n = 214).
• The primary endpoint was the percentage change in body weight from baseline at 72 weeks.

TAKEAWAY

• At 72 weeks, participants without T2D lost a mean of 7.9%, 11.3%, and 13.0% of body weight with 5.5 mg, 9 mg, and 17.2 mg of orforglipron, respectively, compared with 1.6% with placebo. Likewise, participants with T2D lost a mean of 7.5%, 8.3%, and 12.2% of body weight with the respective doses compared to 2.3% with placebo (P < .001 for all).
• By week 72, 61.4% of older adults without T2D and 59.6% of those with T2D achieved at least 10% weight loss with the highest orforglipron dose of 17.2 mg, whereas 9.6% of older adults without T2D and 7.2% of those with T2D achieved this outcome with placebo (P < .001 for all).
• Among participants with T2D, glycemic control improved with orforglipron, with A1c levels decreasing by 1.46%, 1.62%, and 1.66% with 5.5 mg, 9.0 mg, and 17.2 mg of orforglipron, respectively, compared with 0.12% with placebo. Treatment with orforglipron also improved waist circumference, triglyceride levels, and health-related quality of life, regardless of T2D status.
• Gastrointestinal adverse events were more frequent in the orforglipron group. They were generally mild to moderate but also led to treatment discontinuation at higher doses of orforglipron. Serious adverse events, cardiovascular events, renal events, and events possibly related to loss of lean muscle mass were also reported. Hepatic events and level 2 hypoglycemia were rare, with no level 3 hypoglycemic events reported.

IN PRACTICE

“The data presented suggest that orforglipron may be both effective and safe in individuals ≥ 65 years of age, regardless of T2D diagnosis, with a relative safety of orforglipron vs placebo that remained consistent across age groups. Older adults may be more likely to have multiple chronic conditions requiring concomitant medications, increasing the risk of polypharmacy and drug-drug interactions,” the authors wrote. 

“Clinicians should carefully evaluate concomitant medications for potential CYP3A4 interactions when prescribing orforglipron, particularly in older adults who may be more sensitive to changes in drug exposure levels,” they added.

SOURCE

The study was led by Deborah B. Horn, Center for Obesity Medicine and Metabolic Performance, University of Texas McGovern Medical School, Houston. It was published online in Obesity Pillars.

LIMITATIONS

The analysis included a relatively small subgroup of 616 adults aged 65 years or older, which limited more detailed comparisons within the older population. Outcomes were not evaluated in adults aged 75 years or older. Endpoints such as bone density or nutritional status were not assessed, and treatment with orforglipron was not directly compared with other treatments for weight management.

DISCLOSURES

The study was funded by Eli Lilly and Company. Some authors disclosed receiving consulting fees, honoraria, or institutional research support from or serving as consultants or advisors for the funding organization and other biopharmaceutical companies. Four authors declared being employees and shareholders of the funding organization.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.