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Abstract:  
Objective: A male health outcomes investigator, in age bracket 55 – 65, with BMI = 27 kg/m2, but without type 2 diabetes, took compounded tirzepatide 7.5 mg/week therapy as an experiment to see if he could achieve a 10% reduction in body weight over approximately four weeks and restore BMI = 25 kg/m2. Secondary endpoints included maintenance of weight-lifting strength, maintenance of speed and endurance in lap swimming, and maintenance of a nutrient-dense vegan diet. This study was undertaken to address some of the claims currently circulating in popular media about tirzepatide and the glucagon-like peptide 1 receptor agonist (GLP-1 RA) class of injectable drugs. All previous medical journal articles that mention the active pharmaceutical ingredient (API) tirzepatide have referred to the branded drug, while this article is the first one focused on compounded tirzepatide.

Methods: The investigator received weekly subcutaneous injections of 7.5 mg compounded tirzepatide over four weeks at a cost of $400 for four prefilled syringes. In the first, third, and fourth weeks, the investigator received 7.5 mg of compounded tirzepatide as a bolus injection. In week 2, the 7.5 mg dose was distributed over two injections of approximately 3.75 mg each given two days apart. The investigator recorded any lifestyle changes or changes in eating habits that resulted from this short duration study on the effects of tirzepatide for weight loss.

Results: With four weeks of compounded tirzepatide therapy, the investigator achieved a 5% reduction in body weight and a BMI of 25.8. Despite continuing to participate in daily exercise, having a healthy vegan diet, and supplementing with many vitamins, minerals, electrolytes, and nutrient-dense foods, the investigator regained 5% body weight within two weeks after the conclusion of the study. The investigator experienced side effects similar to those reported for GLP-1 RA class of injectable drugs, including tirzepatide. However, the treatment revealed an undulating pattern in which the compounded tirzepatide injection produced the desired effects, but intermittently the patient experienced neither a sense of satiety nor a sense of delayed digestion post injections, therefore, ate a normal meal and/or snacks. Adverse events included generalized bloating and flatulence, carbohydrate-specific temporary weight gain and bloating, intestinal rapid emptying comparable to excessive laxative use, and profound thirst with water consumption approximately double his normal level. Weight-lifting strength was maintained across a wide variety of equipment stations; lap swimming speed was maintained, and endurance was increased on compounded tirzepatide therapy. Apparent negative and positive neuroplasticity in the study period enabled the investigator to overcome a craving for one high caloric sugary snack, and to overcome an endurance barrier in the laps swam per set and per workout. These two results might be explained by performance bias, which arises from behavioral changes by participants or researchers due to awareness of the assigned interventions.

Conclusions: The compounded tirzepatide tested in this 4-week study produced less weight loss than was intended and side effects that would be intolerable in a work environment with nearby colleagues. Compounded tirzepatide was a useful tool to enable this study of the dual glucose-dependent insulinotropic polypeptide (GIP), also known as gastric inhibitory polypeptide, and GLP-1 RA class of drugs in chronic weight management. However, a 7.5 mg weekly dose of compounded API tirzepatide over four weeks is unlikely to produce a lasting 10% reduction in body weight even for those patients practicing intermittent fasting, choosing a vegan diet, and performing weight-bearing exercise and cardiovascular exercise daily. After cessation of therapy, the investigator’s lost weight was regained, representing the weight gain relapse observed in some real-world settings associated with injectable weight loss drugs. Arguably, the dual GIP RA and GLP-1 RA drugs take patients on a proverbial roller coaster ride of weight loss and regain and intense yo-yo dieting. Patients on tirzepatide or semaglutide might benefit most not from realizing some short-term weight loss goal, but from lasting neuroplasticity-like changes in memory, rewards, and elimination of one or more particular food cravings based on the brain’s ability to create, organize, and reorganize connections between neurons.

Related Categories: PEER-REVIEWED, PREVENTIVE MEDICINE/WELLNESS

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