Nutritional status with tirzepatide in obesity: A post hoc analysis of the SURMOUNT-1-4 randomized clinical trials

Nutritional deficiencies are common among people with obesity, before and during treatment, such as with very-low-calorie diets and metabolic/bariatric surgery. Obesity management medications (OMMs) can reduce appetite and dietary intake, potentially affecting nutritional status. The impact of OMMs on nutritional outcomes in people with obesity warrants further study.

We conducted a post hoc analysis of available nutritional status-related data from the randomized, placebo-controlled, phase 3 SURMOUNT-1-4 trials of tirzepatide (N = 4726). Descriptive statistics were utilized to explore available nutritional status-related data from clinical trial reports, including investigator-reported treatment-emergent adverse events (TEAEs) based on 14 MedDRA preferred terms, chosen to identify cases of macronutrient malnutrition; investigator-reported vitamin deficiency-related TEAEs; biomarkers assessed systematically during the trials (albumin; total lymphocyte count [TLC]); reasons for early treatment discontinuation; and participants reaching body mass index (BMI) < 18.5 and < 22 kg/m².

Investigators reported 3 of 14 TEAEs potentially related to macronutrient malnutrition. TEAE incidence of Abnormal loss of weight, Underweight, and Hypoalbuminemia was 0.03 %, 0.06 %, and 0.03 % with tirzepatide and 0 %, 0 %, and 0.06 % with placebo, respectively. Vitamin deficiency-related TEAEs were reported for 0.99 % and 1.07 % of tirzepatide- and placebo-treated participants, respectively. Albumin <3.3 g/dL occurred in 0.06 % and 0.13 % of tirzepatide- and placebo-treated participants, respectively, while TLC <910/μL occurred in 2.90 % and 1.77 %. Treatment discontinuations potentially related to nutritional status (primarily achievement of desired weight and perceived excessive weight loss) occurred in 0.53 % of participants. Overall, 0.38 % and 0.06 % of tirzepatide- and placebo-treated participants reached BMI <18.5 kg/m².

TEAEs and treatment discontinuations due to macronutrient malnutrition were uncommon in the SURMOUNT-1-4 trials of tirzepatide for obesity. Lack of routinely collected vitamin and mineral levels during the trials limited assessment of the impact of tirzepatide treatment on micronutrient status. Systematic assessment of nutritional status before and during OMM treatment would enhance future trials.

NCT04184622 (SURMOUNT-1); NCT04657003 (SURMOUNT-2); NCT04657016 (SURMOUNT-3); and NCT04660643 (SURMOUNT-4).