nference Real-World Evidence Analysis of Nearly 30,000 US Adults 65 and Older on Zepbound (Tirzepatide) for Obesity Documents Low But Nonzero Frailty-Related Concerns: 0.16% Progressive Muscle Mass and Function Decline, 1.6% Malnutrition, 3% Dehydration, and 4.75% Loss of Appetite Across the Cohort Compared With Non-GLP-1 Diabetes Drug and Post-Bariatric-Surgery Comparators; Researchers Encourage Closer Follow-Up Rather Than Discouraging Appropriate GLP-1 Use in Older Adults
US data-analytics firm nference published a real-world evidence analysis this week that compared frailty-related outcomes across three cohorts of US adults 65 and older: nearly 30,000 patients treated with Zepbound (tirzepatide) for obesity, nearly 19,000 receiving non-GLP-1 drugs for type 2 diabetes, and nearly 6,000 who underwent weight-loss surgery. Health records showed progressive declines in muscle mass and function developed in 0.16% of patients across the analysis, malnutrition in 1.6%, dehydration in 3%, and loss of appetite in 4.75%. Lead author Soundararajan's team focused on Zepbound because prior analyses linked tirzepatide with more weight and muscle loss than semaglutide (the active ingredient in Novo Nordisk's Wegovy and Ozempic). The authors said results should not discourage appropriate use of Zepbound or Wegovy in older adults and encouraged closer follow-up of older patients on GLP-1 therapy. The findings arrive as the Medicare GLP-1 Bridge (launched July 1, 2026) expands GLP-1 access to Part D beneficiaries and as prescribers weigh muscle-preservation strategies including selective androgen receptor modulators (SARMs) like Veru's enobosarm and myostatin inhibitors.