{
  "abstract": "Background Orlistat and liraglutide are commonly used for weight management in patients with obesity and type 2 diabetes mellitus (T2DM), but real-world comparative data on metabolic effectiveness and gastrointestinal safety are limited.Methods We performed a retrospective cohort study using the US Collaborative Network on the TriNetX platform. Adults (≥18 years) with obesity (ICD-10 E66.9 or BMI ≥30 kg/m 2) and T2DM (E11) between 01/2015–01/2025 were identified. Two cohorts were defined by first exposure to orlistat or liraglutide after meeting obese-diabetic criteria; liraglutide users with any orlistat exposure were excluded. Propensity score matching (1:1) was performed on demographics, cardiometabolic comorbidities, antidiabetic medications, BMI and HbA1c, yielding 1,909 patients per group. Outcomes over 3 years (days 1–1,095 post-index) included: BMI <30 kg/m2, HbA1c ≤7.0%, a composite of either target, initiation of insulin (insulin-naïve at baseline), gastrointestinal events (diarrhea, noninfective gastroenteritis/colitis), hepatotoxicity, acute pancreatitis, cholelithiasis, kidney stones, and esophageal/gastric cancers. Risks, risk differences, and hazard ratios (HRs; Cox models) were estimated.Results After matching, baseline characteristics were well balanced except for higher BMI and lower HbA1c in the orlistat group. Within 3 years, BMI <30 kg/m 2 was achieved less often with orlistat vs liraglutide (16.6% vs 20.9%; risk difference –4.3%; HR 0.76, 95% CI 0.65–0.88; p<0.001). In contrast, HbA1c ≤7.0% was achieved more frequently and earlier with orlistat (57.9% vs 47.5%; risk difference +10.4%; HR 1.36, 95% CI 1.24–1.48; p<0.001), as was the composite metabolic outcome (62.5% vs 56.9%; risk difference +5.7%; HR 1.16, 95% CI 1.07–1.26; p=0.001). Among insulin-naïve patients, orlistat was associated with a lower 3-year risk of insulin initiation (15.5% vs 27.4%; risk difference –11.9%; HR 0.52, 95% CI 0.43–0.64; p<0.001). Rates of diarrhea, noninfective gastroenteritis/colitis, acute pancreatitis, cholelithiasis, and upper gastrointestinal cancers were similar between groups. Orlistat was associated with higher risks of kidney stones (5.9% vs 4.5%; HR 1.33, 95% CI 1.00–1.76; p=0.048) and rare hepatotoxicity (0.5% vs 0%; p=0.002). (IDDF2026-ABS-0331 Figure 1. 1-3 year metabolic outcomes)Conclusions Liraglutide was more effective for achieving BMI <30 kg/m 2, whereas orlistat was associated with better glycemic target attainment and lower insulin initiation, at the expense of increased kidney stones and rare hepatotoxicity. These trade-offs should inform individualized obesity and diabetes management.Abstract IDDF2026-ABS-0331 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Sheffield Teaching Hospitals and NHS Foundation Trust, United Kingdom"
      ],
      "name": "Arkadeep Dhali"
    },
    {
      "affiliations": [
        "Roswell Park Comprehensive Cancer Center, United States"
      ],
      "name": "Fayaz Khan"
    },
    {
      "affiliations": [
        "Sheffield Teaching Hospitals and NHS Foundation Trust, United Kingdom"
      ],
      "name": "Shruti Gaikwad"
    }
  ],
  "title": "IDDF2026-ABS-0331 Real-world comparative effectiveness and gastrointestinal safety of orlistat versus liraglutide in adults with obesity and type 2 diabetes: a propensity-matched cohort study",
  "uid": "c0648bfe-ef25-5fff-b282-23492f10c0e8"
}