Breakthrough Clinical Results
Eli Lilly and Company announced positive topline results from the Phase 3 ATTAIN-1 trial of orforglipron, an investigational oral GLP-1 receptor agonist. In adults with obesity or overweight with a weight-related medical problem, orforglipron demonstrated significant weight loss at 72 weeks across all three doses compared to placebo. The highest dose (36mg) resulted in an average weight loss of 27.3 lbs (12.4%). Orforglipron also showed improvements in cardiovascular risk factors. Lilly plans to submit orforglipron for regulatory review by year-end and is preparing for a global launch.
Key Highlights
- Orforglipron achieved significant weight loss in adults with obesity (up to 27.3 lbs average weight loss with the 36mg dose).
- The drug met the primary and all key secondary endpoints in the ATTAIN-1 Phase 3 trial.
- Orforglipron demonstrated improvements in cardiovascular risk factors.
- Lilly plans to submit orforglipron for regulatory review by the end of the year.
Clinical Trials of Orforglipron Beyond Obesity
Based on a comprehensive review of available information, there is currently no specific data available regarding clinical trials of Orforglipron for indications other than obesity.
While GLP-1 receptor agonists as a class have been investigated for various conditions including metabolic disorders and cardiovascular conditions, the specific trials for Orforglipron beyond weight management have not been documented in the available information.
Without specific trial data, details regarding the intervention models, dosing regimens, and administration protocols for Orforglipron in non-obesity indications cannot be provided at this time.
The development of Orforglipron appears to be primarily focused on weight management applications based on current publicly available information. As with many investigational medications, the therapeutic applications may expand as research progresses.
For the most current information on Orforglipron's clinical development program, consulting official clinical trial registries such as ClinicalTrials.gov or contacting the pharmaceutical developer directly would be recommended.
Study Design Parameters
Study Design Parameters and Endpoints in Key Obesity Trials
Study Designs
Obesity research employs various study designs to evaluate interventions and assess outcomes:
- Randomized controlled trials (RCTs) are predominantly used to evaluate the effectiveness of pharmacological interventions like orlistat for weight loss or maintenance
- Twenty-three trials were included in a systematic review of orlistat effectiveness
- Cross-sectional community-based surveys assess obesity prevalence, with one study using a two-stage stratified, random sampling technique on 1,239 respondents aged 30+ years
- Cohort design studies examine relationships between solid food introduction timing and obesity risk in infants
- Systematic reviews evaluate evidence for obesity-related cancer trials, with one review including 76 RCTs
- Prospective studies assess obesity's effect on dynamic walking stability, categorizing 53 elderly participants into BMI groups
For anti-obesity medications, trials typically feature: - Double-blind, randomized controlled design for weight loss and maintenance - Inclusion criteria: adult overweight or obese patients - Control groups: placebo or comparison of multiple anti-obesity drugs - Intention-to-treat analysis - Minimum follow-up of one year - Exclusion of abstracts and pseudo-randomized trials - Attrition rates averaging 33% during weight loss phase for orlistat and 43% for sibutramine - Lifestyle modification as a co-intervention for all participants
For GLP-1 receptor agonists, studies assess both weight loss efficacy and safety, with one study examining outcomes in patients with inflammatory bowel disease and obesity.
For bariatric surgery (DSIT), a retrospective review of 116 type 2 diabetic patients was conducted.
Key Endpoints and Outcome Measures
Primary endpoints in obesity trials include:
- Weight loss and maintenance of weight loss
- Changes in obesity-related risk factors including cardiovascular profiles
- ≥5% total weight loss (TWL) at 12-months for GLP-1 RAs
- IBD flares in studies of GLP-1 RAs in inflammatory bowel disease patients
Secondary endpoints include:
- Body Mass Index (BMI) for obesity classification
- Abdominal obesity (51.7%) and truncal obesity (62.1%) measurements
- Center of mass velocity (COMv) and acceleration (COMa) for dynamic stability
- Dynamic balance ability test scale (DBATS) for balance assessment
- Cancer screening participation rates among obese patients
- Cancer risk and mortality associated with obesity
- ≥10% TWL, adverse events, and discontinuation of GLP-1 RAs
- Quality-adjusted life-years (QALYs) in cost-effectiveness studies
- Years in diabetes remission for surgical vs. conventional therapy
Intervention Types
Obesity trials evaluate various interventions:
- Pharmacological interventions including orlistat, simvastatin, and GLP-1 receptor agonists
- Structured exercise with dietary support and behavior therapy
- Bariatric surgery for more rapid weight loss
- Educational interventions to improve cancer screening participation
- Specialized obesity centers (OC) for monitoring obese patients
- Combination therapies such as adding liraglutide to endoscopic bariatric therapy or bariatric surgery
Adverse Events
- Orlistat associated with higher incidence of gastrointestinal adverse events
- GLP-1 RAs caused adverse events in 40% of patients, primarily gastrointestinal (93%)
- Obesity may increase treatment-related adverse effects in cancer therapy
Incidence and Prevalence
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Global Obesity Prevalence and Incidence
The prevalence of obesity has been increasing dramatically in westernized societies, having more than doubled over the last decade in Western and Westernizing countries. Current estimates of the global prevalence of obesity exceed 250 million people as of 2014.
In the United States, obesity prevalence increased from 13% to 32% between the 1960s and 2004, with 66% of adults currently being overweight or obese. Among American youth, 16% of children and adolescents are overweight and 34% are at risk of overweight. A 2023 study identified a national median obesity prevalence of 34.1% across 2,752 US counties.
The global distribution of body mass index (BMI) has increased since the 1980s, albeit with large regional differences. In the US, obesity prevalence increased from 12.0% in 1991 to 17.9% in 1998. Projections indicated that by 2015, 75% of adults would be overweight or obese, and 41% would be obese in the United States.
Prevalence rates for overweight and obesity vary significantly by region. The Middle East, Central and Eastern Europe, and North America have higher prevalence rates. A 2021 study examining obesity across 54 countries from six continents found obesity prevalence ranging from 2.0% in Vietnam to 35.0% in Saudi Arabia.
The prevalence is lowest in Asia and Sub-Saharan Africa, where obesity does not appear to be a public health problem among preschool children. However, in Latin America and the Caribbean, the Middle East and North Africa, and Central Eastern Europe/Commonwealth of Independent States, obesity levels are as high as in the United States.
Annual increases in prevalence ranged from 0.3 to 0.9 percentage points across different demographic groups. During a mean follow-up period of 6 years in the Diogenes cohort, obesity prevalence increased from 13% to 17%.
The linear prediction model predicted an overall obesity prevalence of about 30% in 2015 for European populations, whereas the leveling off model predicted a prevalence of about 20%.
Massive obesity (BMI > 40) corresponds to an increase in mortality ratio, with significant frequency in the USA (13 million subjects), Finland, and South Africa. Recently, an increase in superobesity in childhood has been observed, especially in the United States.
The associations of obesity with gender, age, ethnicity, and socioeconomic status are complex and dynamic. Minority and low-socioeconomic-status groups are disproportionately affected at all ages. Obesity is now usually associated with poverty even in developing countries and is becoming a serious, emerging problem in developing countries.
The global epidemic is considered an unintended consequence of modernization, economic development, urbanization and other societal changes, reflecting overnutrition and sedentary lifestyle.